Anti-MUC16 antibodies and uses thereof

Abstract

To provide anti-MUC16 antibodies and uses thereof.SOLUTION: Provided herein are a composition, a method and use related to an antibody that immunospecifically binds to a glycosylated form of MUC16, a tethered mucin protein. Also provided herein are uses and methods for managing, treating or preventing disorders, such as cancer. Provided are antibodies or antigen binding fragments thereof, and polypeptides including such antibodies or antigen-binding fragments thereof, for example, fusion proteins, conjugates, and / or chimeric antigen receptors as well as cells expressing the same.SELECTED DRAWING: Figure 1A-B

Description

[Technical Field]

[0001] This application was filed on March 17, 2015, and is incorporated herein by reference in its entirety. The benefit of U.S. Provisional Patent Application No. 62 / 134,402 is claimed.

[0002] This application was submitted with a text file entitled "Sequence_Listing_13542-016-228.txt" created on March 14, 2016, and having a size of 375K bytes. The sequence listing provided is incorporated by reference.

[0003] (1. Field) Provided herein are antibodies that immunospecifically bind to the tethered mucin protein MUC16 and inhibit the expression and / or activity of MUC16 for managing, treating, or preventing disorders such as cancer. Modulating antibody compositions, methods, and uses. [Background technology]

[0004] (2.Background) Mucins are important biomolecules for cell homeostasis and epithelial surface protection. Changes in mucin expression in ovarian cancer can be used in diagnosis, prognosis, and treatment (Singh AP et al., Lancet Oncol 2008;9(11):1076-85). MUC16 is expressed in most ovarian cancers. One such mucin is overexpressed and is an established surrogate for the detection and progression of ovarian cancer. The serum marker (CA-125) (Badgwell D et al., Dis Markers 2007;23(5-6):397410; Bast RC, Jr et al., IntJ Gynecol Cancer 2005;15 Suppl 3:274-81; Fritsche HA et al. ClinChem 1998;44(7):1379-80; and Krivak TC et al., Gynecol Oncol 2009;1 15(1):81-5). MUC16 is a highly glycosylated mucin composed of a large cleaved and released domain, called CA-125, consisting of multiple repeat sequences, and a retention domain (MUC-CD) that contains the remaining non-repeated extracellular fragment, transmembrane domain, and cytoplasmic tail (O'Brien TJ et al., Tumor Biol 2001;22(6):348-66). This antigen is otherwise Because it is only expressed at low levels in the uterus, endometrium, fallopian tubes, ovaries, and serosa of the peritoneal and thoracic cavities, MUC16 is a potentially attractive target for immune-based therapy.

[0005] However, the fact that most of the extracellular domain of MUC16 is cleaved and secreted This limits the usefulness of MUC16 as a target antigen on ovarian cancer. Most MUC16 monoclonal antibodies available bind to epitopes present in the large secreted CA-125 fraction of this glycoprotein and not to the retained extracellular fraction of this antigen (MUC-CD). None are known to do so (Bellone S, Am J Obstet Gynecol 2009;200(1):75 el-10; Berek JS, ExpertOpinBiol Ther 2004;4(7):1159-65; O'Brien TJ (IntJ Biol Markers 1998;13(4):188-95). Therefore, the non-released region of MUC16 The generation of new antibodies against these proteins is required for diagnostic and therapeutic approaches. Summary of the Invention

[0006] (3. Overview) Provided are antibodies and antigen-binding fragments thereof, as well as polypeptides, e.g., fusion proteins, conjugates, and / or chimeric antigens, comprising such antibodies or antigen-binding fragments. Among the antibodies and antigen-binding fragments are those that bind to MUC16 receptors and the cells that express them. Some antibodies specifically bind to an epitope on the MUC16 protein. Such antibodies are referred to herein as "MUC16 glycosylation antibodies." Such epitopes are typically epitopes within or substantially within the MUC16 molecule, usually the extracellular portion of the non-shed form of MUC16. In some embodiments, the epitope is not within the tandem repeat region of MUC16 and / or secreted forms of MUC16, or the antibody or fragment does not bind to the tandem repeat region of MUC16 and / or secreted forms of MUC16. The epitope is within or includes residues within MUC16, typically including one or more glycosylated residues or glycosylation sites therein. In such a case, the epitope may be located at one or more glycosylation sites, e.g., at an N-glycosylation site. In some embodiments, the epitope comprises an asparagine residue corresponding to Asn1806 or Asn1800 of the MUC16 sequence set forth in SEQ ID NO: 150 (and / or a glycosylated form thereof). In some embodiments, the epitope comprises the Asn1806 corresponding to SEQ ID NO: 150. containing a paragine residue but not an asparagine residue corresponding to Asn1800 in SEQ ID NO: 150; In some embodiments, the epitope includes an asparagine residue corresponding to Asn1800 of SEQ ID NO: 150, but does not include an asparagine residue corresponding to Asn1806 of SEQ ID NO: 150. In some of any of such embodiments, such one or more asparagines are glycosylated. In some embodiments, the antibody or antigen-binding fragment binds to an epitope within SEQ ID NO: 131 or an epitope including an internal residue of SEQ ID NO: 131; In some embodiments, the epitope comprises a nucleotide sequence, ... In this case, the antibody or fragment may be a fragment of the MUC16 fragment corresponding to SEQ ID NO: 168, or a fragment of the MUC16 fragment corresponding to SEQ ID NO: 168. Even within groups 2 to 19, there is no immunospecific binding.

[0007] In some embodiments, the provided antibodies or antigen-binding fragments comprise the heavy and / or light chains of the antibody sequences described herein, e.g., the MUC16-glycosylation site-targeting antibody sequences, e.g., the antibody designated 18C6, the antibody designated 10C6, and / or the antibody designated 19C11. In some embodiments, the complementarity determining region (CDR) of each of the amino acid sequences of the target amino acid sequence is 0 or 1. The antibody or fragment may have one of the heavy chain sequences provided herein, e.g., designated 18C6. In some embodiments, the antibody has a heavy chain CDR3 (HCDR3) having a sequence corresponding to the HCDR3 of the heavy chain sequence of the antibody designated as 10C6, the antibody designated as 19C11, and / or the antibody designated as 7B12. [ka] (where X 18 is T, A, or S); SEQ ID NO:5; SEQ ID NO:25; SEQ ID NO:45; SEQ ID NO:65; and SEQ ID NO:85; SEQ ID NOs:31, 51, 71, and 91; SEQ ID NO:17; SEQ ID NO:37; SEQ ID NO:57; SEQ ID NO: No. 77; and SEQ ID NO: 97.

[0008] In some embodiments, the provided antibodies or antigen-binding fragments comprise a heavy chain HCDR1 having a sequence corresponding to the CDR1 (HCDR1) of the heavy chain sequence of one of the heavy chain sequences provided herein, e.g., the antibody designated 18C6, the antibody designated 10C6, the antibody designated 19C11, and / or the antibody designated 7B12. In some embodiments, the HCDR1 is [ka] (wherein X1 is L or V), the sequence [ka] (wherein X8 is N or S and X9 is L or V), [ka] (where X 15 is N or S, and X 16 is V or L), and shown as SEQ ID NO: 3 the sequence shown as SEQ ID NO: 9; and the sequence shown as SEQ ID NO: 15. and the sequence set forth in any of SEQ ID NOs: 23, 43, 63, 83; and the sequence set forth in any of SEQ ID NOs: 29, 49, 69, and 89; and the sequence set forth in SEQ ID NO: 35 , 55, 75, and 95.

[0009] In some embodiments, the provided antibodies or antigen-binding fragments comprise a heavy chain HCDR2 having a sequence corresponding to the CDR2 (HCDR2) of the heavy chain sequence of one of the heavy chain sequences provided herein, e.g., the antibody designated 18C6, the antibody designated 10C6, the antibody designated 19C11, and / or the antibody designated 7B12. [ka] (wherein X2 is E or absent and X3 is Y or N); [ka] (where X 10 is E or absent); [ka] (where X 17 is E or absent); the sequence shown as SEQ ID NO: 4; and SEQ ID NO: 10 and the sequence set forth as SEQ ID NO: 16; and the sequence set forth as any of SEQ ID NOs: 24, 44, 64, 84; and the sequence set forth as any of SEQ ID NOs: 30, 50, 70, 90 and the sequence set forth in any of SEQ ID NOs: 36, 56, 76, and 96. The array has an array selected from among the columns.

[0010] In some embodiments, including any of the foregoing embodiments, the provided antibody or antigen-binding fragment has one of the light chain sequences provided herein, e.g., designated 18C6. In some embodiments, the antibody designated as 10C6, the antibody designated as 19C11, and / or the antibody designated as 7B12 comprises, e.g., further comprises, a light chain LCDR3 having a sequence corresponding to the CDR3 (LCDR3) of the light chain sequence of [ka] (wherein X6 is G or S and X7 is H or Y); [ka] (where X 13 is G or S and X 14 is H or Y); and [ka] a sequence selected from among SEQ ID NOs: 8, 28, 48, 68, and 88; a sequence selected from among SEQ ID NOs: 14, 34, 54, 74, and and 94; and a sequence selected from SEQ ID NOs: 20, 4, 60, 80, and 100. The sequence is selected from the sequences listed below.

[0011] In some embodiments, including any of the foregoing embodiments, the provided antibody or antigen-binding fragment has one of the light chain sequences provided herein, e.g., designated 18C6. In some embodiments, the antibody may further comprise a light chain LCDR1 having a sequence corresponding to the CDR1 (LCDR1) of the light chain sequence of the antibody designated as 10C6, the antibody designated as 19C11, and / or the antibody designated as 7B12. [ka] (where X 11 is L or R, and X 12 is H or K); [ka] (where X 19 is V or L, and X 20 is H or K); a sequence selected from among SEQ ID NOs: 6, 26, 46, 66, and 86; a sequence selected from among SEQ ID NOs: 12, 32, 52, 72, and 92; and a sequence selected from among SEQ ID NOs: 18, 38, 58, 78, and 98.

[0012] In some embodiments, including any of the foregoing embodiments, the provided antibody or antigen-binding fragment has, for example, one of the light chain sequences provided herein, e.g., 18C6. In some embodiments, the antibody designated as 10C6, the antibody designated as 19C11, and / or the antibody designated as 7B12 further comprises, for example, a light chain LCDR2 having a sequence corresponding to the CDR2 (LCDR2) of the light chain sequence of the antibody designated as [ka] and SEQ ID NOs: 7, 27, 47, 67, 87; 13, 33, 53, 73, 93, 19, 39, 59, 79, 99, 119 The sequence may be selected from the sequences shown in any of the following:

[0013] Among the antibodies and antigen-binding fragments of any of the embodiments, there is provided: (a) the amino acid sequence [ka] (b) a VH complementarity-determining region (CDR) 1 comprising the amino acid sequence: [ka] (wherein X2 is E or absent and X3 is Y or N); and (c) a VHCDR2 comprising amino acid sequence [ka] Some have a VHCDR3 containing

[0014] Among the antibodies and antigen-binding fragments of any of the embodiments, there is provided: (a) the amino acid sequence [ka] (b) a VHCDR1 comprising the amino acid sequence column [ka] (where X 10 is E or absent); and (c) a VHCDR2 comprising the amino acid sequence [ka] Some have a VHCDR3 containing

[0015] Among the antibodies and antigen-binding fragments of any of the embodiments, there is provided: (a) the amino acid sequence [ka] (where X 15 is N or S, and X 16 is V or L); (b) an amino acid array [ka] (where X 17 is E or absent); and (c) a VHCDR2 comprising the amino acid sequence [ka] (where X 18 is T, A, or S).

[0016] Among the antibodies and antigen-binding fragments of any of the embodiments, there are those comprising the amino acid sequence of SEQ ID NO:3. VH CDR1 comprising the amino acid sequence of SEQ ID NO: 4, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 5, VH CDR3 comprising the amino acid sequence of SEQ ID NO: 9; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 10 CDR2, and V comprising the amino acid sequence of SEQ ID NO: 11; CDR3; V comprising the amino acid sequence of SEQ ID NO: 15 H CDR1 comprising the amino acid sequence of SEQ ID NO: 16, and VH CDR2 comprising the amino acid sequence of SEQ ID NO: 17. VH CDR3 comprising the amino acid sequence of SEQ ID NO: 23; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 24 CDR2, and VHCDR3 comprising the amino acid sequence of SEQ ID NO: 25; VH CDR1, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and VH CDR3 comprising the amino acid sequence of SEQ ID NO: 31; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 35, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 36 VH comprising a CDR2 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 37; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 44, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 45 VH CDR3 comprising the amino acid sequence of SEQ ID NO: 49; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 50; VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 51; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 56, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 57 VH CDR3 comprising the amino acid sequence of SEQ ID NO: 63; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 64 VH CDR2 comprising the amino acid sequence of SEQ ID NO: 65; and VH CDR3 comprising the amino acid sequence of SEQ ID NO: 69 VH CDR1 comprising the amino acid sequence of SEQ ID NO: 70, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 71; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 75, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 76 and VH CDR3 comprising the amino acid sequence of SEQ ID NO: 77; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 83, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 84, and VH CDR3 comprising the amino acid sequence of SEQ ID NO: VH CDR3 comprising the amino acid sequence of SEQ ID NO: 85; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 89; 0, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 91; VH CDR1 comprising the amino acid sequence of SEQ ID NO: 95, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and VH CDR3 comprising the amino acid sequence of SEQ ID NO: 97. and those having a VH comprising a VH CDR3 comprising the amino acid sequence of SEQ ID NO:97.

[0017] Among the antibodies and antigen-binding fragments of any of the embodiments, there is provided: (a) the amino acid sequence [ka] (b) a VLCDR1 comprising the amino acid sequence column [ka] and (c) an amino acid sequence [ka] (wherein X6 is G or S and X7 is H or Y) Some have this.

[0018] Among the antibodies and antigen-binding fragments of any of the embodiments, there is provided: (a) the amino acid sequence [ka] (where X 11 is L or R, and X 12 is H or K); (b) an amino acid (c) a VLCDR2 comprising the sequence YMS (SEQ ID NO: 113); and (d) an amino acid sequence [ka] (where X 13is G or S and X 14 is H or Y).

[0019] In the antibodies and antigen-binding fragments of any of the embodiments, there is provided an antibody having the amino acid sequence [ka] (where X 19 is V or L, and X 20 is H or K); (b) an amino acid (c) VLCDR2 comprising the sequence YMS (SEQ ID NO: 119); and (d) the amino acid sequence [ka] Some have a VLCDR3 containing

[0020] Among the antibodies and antigen-binding fragments of any of the embodiments, there is a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and an amino acid sequence of SEQ ID NO: 28. or a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 32, the amino acid sequence of SEQ ID NO: 33 and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 34; or a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 38 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 39, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 40 or VL CDR3 comprising the amino acid sequence of SEQ ID NO: 46; or VL CDR1 comprising the amino acid sequence of SEQ ID NO: 47; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 48, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 5; or a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 5 VL CDR1 comprising the amino acid sequence of SEQ ID NO:2, VL CDR2 comprising the amino acid sequence of SEQ ID NO:53, and VL CDR3 comprising the amino acid sequence of SEQ ID NO:44. VL CDR3 comprising the amino acid sequence of SEQ ID NO: 54; or VL CDR1 comprising the amino acid sequence of SEQ ID NO: 58, sequence a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 60; or VL CDR1 comprises the amino acid sequence of SEQ ID NO: 86, VL CDR2 comprises the amino acid sequence of SEQ ID NO: 87, and VLCDR3 comprising the amino acid sequence of SEQ ID NO: 88; or VLC comprising the amino acid sequence of SEQ ID NO: 92 DR1, VLCDR2 comprising the amino acid sequence of SEQ ID NO: 93, and VL comprising the amino acid sequence of SEQ ID NO: 94 CDR3; or VLCDR1 comprising the amino acid sequence of SEQ ID NO: 98, VLCDR2 comprising the amino acid sequence of SEQ ID NO: 99 L CDR2, and VLCDR3 comprising the amino acid sequence of SEQ ID NO: 100; or VLCDR3 comprising the amino acid sequence of SEQ ID NO: 6 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 7, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 8 or VL CDR3 comprising the amino acid sequence of SEQ ID NO: 12, the amino acid sequence of SEQ ID NO: 13 and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 14; or a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 18 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 19, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 20 or VL CDR3 comprising the amino acid sequence of SEQ ID NO: 66; or VL CDR1 comprising the amino acid sequence of SEQ ID NO: 67; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 68, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 7; or a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 7 VL CDR1 comprising the amino acid sequence of SEQ ID NO:2, VL CDR2 comprising the amino acid sequence of SEQ ID NO:73, and VL CDR3 comprising the amino acid sequence of SEQ ID NO:44. VL CDR3 comprising the amino acid sequence of SEQ ID NO: 74; or VL CDR1 comprising the amino acid sequence of SEQ ID NO: 78, and VL CDR2 comprising the amino acid sequence of SEQ ID NO: 79, and VL CDR3 comprising the amino acid sequence of SEQ ID NO: 80. There is something to do.

[0021] Among the antibodies and antigen-binding fragments of any of the embodiments, (a)(i) the amino acid sequence [ka] wherein X1 is L or V; [ka] wherein X2 is E or absent and X3 is Y or N; and amino acid sequence [ka] and (ii) a VH comprising a VH CDR3 comprising the amino acid sequence [ka] wherein X4 is R or L and X5 is K or H; Acid sequence [ka] and a VLCDR2 comprising the amino acid sequence [ka] (wherein X6 is G or S, and X7 is H or Y) L; or (b)(i) an amino acid sequence [ka] wherein X8 is N or S and X9 is L or V; Acid sequence [ka] (where X10 is E or absent); and [ka] and (ii) a VH comprising a VH CDR3 comprising the amino acid sequence [ka] (where X 11 is L or R and X 12 VLCDR1 containing the amino acid sequence (H or K); VLCDR2 containing the amino acid sequence YMS (SEQ ID NO: 113); and the amino acid sequence [ka] (where X 13 is G or S and X 14 VLCDR3 containing or (c)(i) an amino acid sequence [ka] (where X 15 is N or S and X 16 VHCDR1 containing the amino acid sequence (V or L); Acid sequence [ka] (where X 17 is E or absent); and [ka] (where X 18 is T, A, or S); and (ii) a VHCDR3 comprising the amino acid sequence [ka] (where X 19 is V or L, and X 20 VLCDR1 containing the amino acid sequence (H or K); VLCDR2 containing the amino acid sequence YMS (SEQ ID NO: 119); and the amino acid sequence [ka] (d)(i) a VL comprising a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 23; or (d)(i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 2 a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and (ii) VLCDR1 comprising the amino acid sequence of SEQ ID NO: 26, VL comprising the amino acid sequence of SEQ ID NO: 27 (e) a VL comprising a CDR2, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 28; or (e) (i) a VL comprising a CDR2, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 29 VH CDR1 comprising the amino acid sequence of SEQ ID NO: 30, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 31 (ii) a VH comprising a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 32; and (ii) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 32. , VLCDR2 comprising the amino acid sequence of SEQ ID NO: 33, and VLCDR3 comprising the amino acid sequence of SEQ ID NO: 34. or (f)(i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 35, the amino acid sequence of SEQ ID NO: 36; a VH comprising a VH CDR2 comprising the sequence, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and (ii) a VH comprising the sequence VL CDR1 comprising the amino acid sequence of SEQ ID NO: 38, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 39, and (g) a VL comprising a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 40; or (g) (i) a VL comprising the amino acid sequence of SEQ ID NO: 43 a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 44, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 45, (ii) a VH comprising a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 46; and (iii) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 4 a VL comprising a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 48; or (h) (i) VH CDR1 comprising the amino acid sequence of SEQ ID NO: 49, VH CDR1 comprising the amino acid sequence of SEQ ID NO: 50 (ii) a VH comprising a VH CDR2 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 51; and (iii) a VH comprising a VH CDR2 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 52. VL CDR1 comprising the amino acid sequence of SEQ ID NO: 53, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 54 (i) a VL comprising a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 55; or (i) a VH CDR comprising the amino acid sequence of SEQ ID NO: 55. 1. VH CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and VH C comprising the amino acid sequence of SEQ ID NO: 57 and (ii) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 59; and a VL comprising a VL CDR2 comprising the sequence, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 60; or (j)(i) VH CDR1 comprising the amino acid sequence of SEQ ID NO: 83, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 84, and and a VH comprising a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 85; and (ii) an amino acid sequence of SEQ ID NO: 86. (k)(i) a VL comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 89, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 89, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 89; or (k)(i) a VL comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 89, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 89, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 90, and VH CDR3 comprising the amino acid sequence of SEQ ID NO: 91. VH; and (ii) VLCDR1 comprising the amino acid sequence of SEQ ID NO: 92, VLCDR1 comprising the amino acid sequence of SEQ ID NO: 93. (l) a VL comprising a VL CDR2 and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 94; or (l) (i) SEQ ID NO: 95 a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 96, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 97, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 98; R1, VLCDR2 comprising the amino acid sequence of SEQ ID NO: 99, and VL comprising the amino acid sequence of SEQ ID NO: 100 or (m)(i) a VL comprising the amino acid sequence of SEQ ID NO: 3, CDR3; or (m)(i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 4 a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 5; and (ii) a VH comprising the sequence VL CDR1 comprising the amino acid sequence of SEQ ID NO: 6, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and (n) a VL comprising a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 8; or (n) (i) a VL comprising the amino acid sequence of SEQ ID NO: 9 VH CDR1 comprising the amino acid sequence of SEQ ID NO: 10, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 11 and (ii) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 12, a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 13. a VL comprising a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 14; or (o) (i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 16, (ii) a VH comprising CDR2, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 17; and (iii) a VH comprising the amino acid sequence of SEQ ID NO: 18. VL CDR1 comprising the amino acid sequence of SEQ ID NO: 19, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 20 (p)(i) a VL comprising a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 63; or (p)(i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 63. , VH CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and VH CD comprising the amino acid sequence of SEQ ID NO: 65 and (ii) a VLCDR1 comprising the amino acid sequence of SEQ ID NO: 66, a VLCDR2 comprising the amino acid sequence of SEQ ID NO: 67, and a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 68. a VL comprising a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 68, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 69; or (q)(i) a VL comprising the sequence VH CDR1 comprising the amino acid sequence of SEQ ID NO: 69, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 70, and (ii) a VH comprising a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 71; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 72 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 73, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 74 or (r) (i) a VL comprising a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 75; or (r) (i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 7 a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 77; and (ii) VLCDR1 comprising the amino acid sequence of SEQ ID NO: 78, VL comprising the amino acid sequence of SEQ ID NO: 79 and a VL comprising a CDR2 and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:80.

[0022] Among the antibodies and antigen-binding fragments of any of the embodiments, (a)(i) [ka] (where X 21 is T or N, and X 22 is I or K, and X 23 is N or S, and X 24 is V or L, and X 25 is S or I, and X 26 is P or S, and X 27 is E or non-existent, and X 28 is N or Y, and X 29 is K or R, and X 30 is A or D, and X 31 is T or S, and X 32 is V or A, and X 33 teeth , G or D, and X 34is T, I, or S, and X 35 is T, S, or A); and (ii) a VH comprising the amino acid sequence [ka] (where X 36 is I or V, and X 37 is P or S, and X 38 is R or L, and X 39 is K or H, and X 40 is R or K, and X 41 is E or G, and X 42 is S or G and X 43 VL comprising the amino acid sequence or (b) (i) a VH comprising the amino acid sequence of SEQ ID NO: 1; and (ii) a VL comprising the amino acid sequence of SEQ ID NO: 2; or (c) (i) a VH comprising the amino acid sequence of SEQ ID NO: 21; and (ii) an amino acid sequence of SEQ ID NO: 22 or (d) (i) a VH comprising the amino acid sequence of SEQ ID NO: 41; and (ii) a VL comprising the amino acid sequence of SEQ ID NO: 42; or (e) (i) a VH comprising the amino acid sequence of SEQ ID NO: 61; and (ii) a VL comprising the amino acid sequence of SEQ ID NO: 62; or (f) (i) a VH comprising the amino acid sequence of SEQ ID NO: 81; and (ii) a VL comprising the amino acid sequence of SEQ ID NO: 82.

[0023] Also provided are antibodies or antigen-binding fragments that have at least 90, 95, 96, 97, 98, 99, or 100% identity to the VH and / or VL sequence of any such antibody and / or any of the antibodies shown in Tables 1 and 2. Also provided are antibodies or fragments thereof that have at least 90, 95, 96, 97, 98, 99, or 100% identity to the VH and / or VL sequence of any such antibody and / or any of the antibodies shown in Tables 1 and 2. , which compete with any of such antibodies for binding to MUC16 and / or its epitopes.

[0024] Also provided are fusion proteins, e.g., chimeric molecules and / or conjugates comprising any of the antibodies, e.g., chimeric antigen receptors (CARs) containing such antibodies or fragments, and cells expressing such molecules. Also provided are humanized versions of any such antibodies.

[0025] In some embodiments, provided herein are antibodies or antigen-binding fragments thereof, wherein the antibodies bind to (a) a first form of MUC16, which first form is glycosylated (b) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (b) lacks immunospecific binding to cells recombinantly expressing a second form of MUC16, which second form is non-glycosylated, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (c) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. In one embodiment, (i) the cells recombinantly expressing the first form of MUC16 are SKOV3 cells; (ii) the cells recombinantly expressing the second form of MUC16 inhibit matrigel invasion in vitro. and (iii) the cells in step (c) are SKOV3 cells. wherein the antibody lacks immunospecific binding to cells recombinantly expressing a third form of MUC16, which third form is glycosylated, and wherein the amino acid sequence of the third form is SEQ ID NO: 139. In certain embodiments, (i) the cells recombinantly expressing the first form of MUC16 are SKOV3 cells; (ii) the cells recombinantly expressing the second form of MUC16 are SKOV3 cells; and (iii) the cells in step (c) are SKOV3 cells. In certain embodiments, (i) the cells recombinantly expressing the first form of MUC16 are SKOV3 cells; (ii) the cells recombinantly expressing the second form of MUC16 are SKOV3 cells. (iii) the cells recombinantly expressing said third form of MUC16 are SKOV3 cells; and (iv) the cells of step (c) are SKOV3 cells.

[0026] Also provided herein is an antibody or antigen-binding fragment thereof, wherein the antibody is an antibody or antigen-binding fragment thereof that binds to (a) a first form of MUC16, which first form is glycosylated, wherein the first form is (b) immunospecifically binds to cells recombinantly expressing a third form of MUC16 (wherein the amino acid sequence of the second form is SEQ ID NO: 133); (b) lacks immunospecific binding to cells recombinantly expressing a third form of MUC16 (wherein the third form is glycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139); and (c) inhibits in vitro matrigel invasion of cells recombinantly expressing the first form of MUC16. In certain embodiments, (i) the cell recombinantly expressing the first form of MUC16 is a SKOV3 cell; (ii) the cell recombinantly expressing the third form of MUC16 is a SKOV3 cell; and (iii) the cell in step (c) is a SKOV3 cell.

[0027] In certain embodiments, the antibody or antigen-binding fragment thereof immunospecifically binds to an epitope comprising N-glycosylated asparagine 1806 of SEQ ID NO:150.

[0028] In certain embodiments, the antibody or antigen-binding fragment thereof has the amino acid sequence [ka] (where, [ka] The amino acid residues 4 (N4) and 10 (N10) of In one embodiment, the antibody or antigen-binding fragment thereof has the amino acid sequence [ka] (where, [ka] wherein amino acid residue number 7 (N7) is glycosylated. In certain embodiments, the glycosylation consists of N-linked chitobiose.

[0029] In certain embodiments, the antibody or antigen-binding fragment thereof is a human antibody that expresses a first form of MUC16. When a cell containing the antibody or antigen-binding fragment is contacted with the antibody or antigen-binding fragment, it is internalized by the cell. In certain embodiments, the cell is a SKOV3 cell recombinantly expressing the first form of MUC16.

[0030] In certain embodiments, the antibody or antigen-binding fragment thereof binds to a glycosylated form of MUC16. Inhibits the growth of tumors that develop.

[0031] In certain embodiments, the antibody is a monoclonal antibody.

[0032] In certain embodiments, the antibody or antigen-binding fragment thereof comprises: (a) the amino acid sequence [ka] (b) a VH complementarity-determining region (CDR) 1 comprising the amino acid sequence: [ka] (wherein X2 is E or absent and X3 is Y or N); and (c) a VHCDR2 comprising amino acid sequence [ka] The heavy chain variable region (VH) comprises a VH CDR3 comprising:

[0033] In certain embodiments, the antibody or antigen-binding fragment thereof comprises: (a) the amino acid sequence [ka] (b) a VHCDR1 comprising the amino acid sequence column [ka] (where X 10 is E or absent); and (c) a VHCDR2 comprising the amino acid sequence [ka] and a VH comprising a VH CDR3 comprising:

[0034] In certain embodiments, the antibody or antigen-binding fragment thereof comprises: (a) the amino acid sequence [ka] (where X 15 is N or S, and X 16 is V or L); (b) an amino acid array [ka] (where X 17 is E or absent); and (c) a VHCDR2 comprising the amino acid sequence [ka] (where X 18 is T, A, or S).

[0035] In certain embodiments, the antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO:3. VH CDR1 comprising the amino acid sequence of SEQ ID NO: 4, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 5 VH comprising VH CDR3.

[0036] In certain embodiments, the antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO:9. VH CDR1 comprising the amino acid sequence of SEQ ID NO: 10, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 11 and a VH comprising a VH CDR3 comprising:

[0037] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 17. and a VH comprising a VH CDR3 comprising:

[0038] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 25. and a VH comprising a VH CDR3 comprising:

[0039] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 29, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 31. and a VH comprising a VH CDR3 comprising:

[0040] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 35, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 37. and a VH comprising a VH CDR3 comprising:

[0041] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 43, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 45. and a VH comprising a VH CDR3 comprising:

[0042] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 49, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 51. and a VH comprising a VH CDR3 comprising:

[0043] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 55, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 57. and a VH comprising a VH CDR3 comprising:

[0044] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 63, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 65. and a VH comprising a VH CDR3 comprising:

[0045] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 69, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 71. and a VH comprising a VH CDR3 comprising:

[0046] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 75, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 76, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 77. and a VH comprising a VH CDR3 comprising:

[0047] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 83, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 84, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 85. Contains a VHCDR3 containing

[0048] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 89, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 90, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 91. and a VH comprising a VH CDR3 comprising:

[0049] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 95, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 97. and a VH comprising a VH CDR3 comprising:

[0050] In certain embodiments, the antibody or antigen-binding fragment thereof comprises: [ka] (where X 21 is T or N, and X 22 is I or K, and X 23 is N or S, and X 24 is V or L, and X 25 is S or I, and X 26 is P or S, and X 27 is E or non-existent , X 28 is N or Y, and X 29 is K or R, and X 30 is A or D, and X 31 is T or S, and X 32 is V or A, and X 33 is G or D, and X 34 is T, I, or S, and X 35 is T, S, or A).

[0051] In certain embodiments, the antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO:1. VH containing

[0052] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO:21.

[0053] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO:41.

[0054] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO:61.

[0055] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO:81.

[0056] In certain embodiments, the antibody or antigen-binding fragment thereof comprises: (a) the amino acid sequence [ka] (b) a VLCDR1 comprising the amino acid sequence column [ka] and (c) an amino acid sequence [ka] (wherein X6 is G or S and X7 is H or Y), Contains variable region (VL).

[0057] In certain embodiments, the antibody or antigen-binding fragment thereof comprises: (a) the amino acid sequence [ka] (where X 11 is L or R, and X 12 is H or K); (b) an amino acid (c) a VLCDR2 comprising the sequence YMS (SEQ ID NO: 113); and (d) an amino acid sequence [ka] (where X 13 is G or S and X 14 VL comprises VLCDR3 comprising VL CDR3, VL C ... include.

[0058] In certain embodiments, the antibody or antigen-binding fragment thereof comprises: (a) the amino acid sequence [ka] (where X 19 is V or L, and X 20 is H or K); (b) an amino acid (c) VLCDR2 comprising the sequence YMS (SEQ ID NO: 119); and (d) the amino acid sequence [ka] VL comprising VLCDR3 comprising VL.

[0059] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 28. and a light chain variable region (VL) comprising a VLCDR3 comprising:

[0060] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 32, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 33, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 34. VL comprising VLCDR3 comprising VL.

[0061] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 38, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 39, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 40. VL comprising VLCDR3 comprising VL.

[0062] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 46, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 47, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 48. VL comprising VLCDR3 comprising VL.

[0063] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 52, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 54. VL comprising VLCDR3 comprising VL.

[0064] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 58, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 60. VL comprising VLCDR3 comprising VL.

[0065] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 86, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 87, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 88. VL comprising VLCDR3 comprising VL.

[0066] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 92, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 93, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 94. VL comprising VLCDR3 comprising VL.

[0067] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 98, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 99, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 100. Contains VLCDR3, which contains VL.

[0068] In certain embodiments, the antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO:6. VL CDR1 comprising the amino acid sequence of SEQ ID NO: 7, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 8 comprising a VL comprising a VL CDR3.

[0069] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 12, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 14. VL comprising VLCDR3 comprising VL.

[0070] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 20. VL comprising VLCDR3 comprising VL.

[0071] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 66, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 67, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 68. VL comprising VLCDR3 comprising VL.

[0072] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 72, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 74. VL comprising VLCDR3 comprising VL.

[0073] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 78, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 79, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 80. VL comprising VLCDR3 comprising VL.

[0074] In certain embodiments, the antibody or antigen-binding fragment thereof comprises: [ka] (where X 36 is I or V, and X 37 is P or S, and X 38 is R or L, and X 39 is K or H, and X 40 is R or K, and X 41 is E or G, and X 42 is S or G, and X 43 is Y or H).

[0075] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO:22.

[0076] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO:42.

[0077] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO:82.

[0078] In certain embodiments, the antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO:2. Contains VL.

[0079] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO:62.

[0080] In certain embodiments, the antibody comprises human-derived heavy and light chain constant regions. In certain embodiments, the heavy chain constant region has an isotype selected from the group consisting of gamma 1, gamma 2, gamma 3, and gamma 4. In certain embodiments, the light chain constant region has an isotype selected from the group consisting of kappa and lambda.

[0081] In certain embodiments, the antibody or antigen-binding fragment thereof is humanized. In certain embodiments, the antibody or antigen-binding fragment thereof is a humanized form of a rodent antibody.

[0082] In certain embodiments, the antibody is an immunoglobulin comprising two identical heavy chains and two identical light chains. In certain embodiments, the immunoglobulin is an IgG.

[0083] Also provided herein is an antibody conjugate comprising an antibody or antigen-binding fragment thereof provided herein conjugated to an agent. In certain embodiments, the agent is an imaging agent or a cytotoxic agent.

[0084] In certain embodiments, the antibody or antigen-binding fragment thereof is a bispecific antibody. In certain embodiments, the bispecific antibody immunospecifically binds to CD3. wherein the bispecific antibody comprises an immunoglobulin that immunospecifically binds to MUC16, wherein the light chain of the immunoglobulin immunospecifically binds to CD3 via a peptide linker. The bispecific antibody conjugate comprises a bispecific antibody provided herein conjugated to a single-chain variable fragment (scFv) encoding the antibody. Also provided herein is a bispecific antibody conjugate comprising a bispecific antibody provided herein conjugated to an agent. In certain embodiments, the agent is an imaging agent or a cytotoxic agent.

[0085] In some embodiments, the antigen-binding fragment is a single-chain variable fragment (scFv). Also provided herein is an scFv conjugate comprising the scFv provided herein conjugated to a drug. In some embodiments, the drug is an imaging agent or a cytotoxic agent.

[0086] Also provided herein are fusion proteins, chimeric molecules, and conjugates comprising the antibodies and antigen-binding fragments. Chimeric antigen receptors (CARs) comprising one or more of any of the provided antibodies or antigen-binding fragments thereof, such as a CAR comprising any of the scFvs provided herein or scFv conjugates provided herein; and / or a CAR comprising an antigen-binding domain that competes with it for binding to MUC16.

[0087] Also provided herein are antibody heavy chains or antigen-binding portions thereof. Among the antibodies and antigen-binding fragments thereof provided are those having heavy chains and / or antigen-binding portions thereof, e.g., VH regions thereof; such heavy chains and antigen-binding portions thereof are also provided. In embodiments, the heavy chain, or antigen-binding portion thereof, comprises (a) the amino acid sequence [ka] (b) a VHCDR1 comprising the amino acid sequence [ka] (wherein X2 is E or absent and X3 is Y or N); and (c) a VHCDR2 comprising amino acid sequence [ka] wherein optionally, the antibody heavy chain or antigen-binding portion thereof comprises a VH comprising a VH CDR3 comprising The antibody or antigen-binding fragment thereof comprises: (i) a first form of MUC16, which first form is glycosylated; (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is glycosylated (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits cell invasion into Matrigel in vitro.

[0088] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises: (a) the amino acid sequence [ka] (b) a VHCDR1 comprising the amino acid sequence column [ka] (where X 10 is E or absent); and (c) a VHCDR2 comprising the amino acid sequence [ka] wherein optionally, the antibody heavy chain or antigen-binding portion thereof comprises a VH comprising a VH CDR3 comprising The antibody or antigen-binding fragment thereof comprises: (i) a first form of MUC16, which first form is glycosylated; (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is glycosylated (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits cell invasion into Matrigel in vitro.

[0089] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises: (a) the amino acid sequence [ka] (where X 15 is N or S, and X 16 is V or L); (b) an amino acid array [ka] (where X 17 is E or absent); and (c) a VHCDR2 comprising the amino acid sequence [ka] (where X 18 is T, A, or S); The antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof comprises: (i) a first form of MUC16, which first form is glycosylated, wherein the first form has the amino acid sequence is SEQ ID NO: 133); (ii) a second form of MUC16, which second form is non-glycosylated, wherein the amino acid sequence of the second form is is SEQ ID NO: 139); and (iii) inhibits matrigel invasion in vitro of cells recombinantly expressing said first form of MUC16.

[0090] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises the amino acid sequence of SEQ ID NO: 3. VH CDR1 comprising the sequence of SEQ ID NO: 4, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 5 wherein optionally, the antibody heavy chain or antigen-binding portion thereof comprises a VH comprising a VH CDR3 comprising the sequence The antibody or antigen-binding fragment thereof comprises: (i) a first form of MUC16 (wherein the first form is glycosylated) (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of cells in vitro.

[0091] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises the amino acid sequence of SEQ ID NO: 9. VH CDR1 comprising the amino acid sequence of SEQ ID NO: 10, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 11 and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0092] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 17. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0093] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 25. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0094] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 29, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 31. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0095] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 35, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 37. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0096] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 43, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 45. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0097] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 49, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 51. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0098] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 55, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 57. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0099] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 63, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 65. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0100] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 69, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 71. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0101] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 75, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 76, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 77. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0102] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 83, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 84, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 85. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0103] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 89, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 90, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 91. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0104] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 95, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 97. and optionally, the antibody heavy chain or antigen-binding portion thereof, The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0105] In some embodiments, the heavy chain, or antigen-binding portion thereof, [ka] (where X 21 is T or N, and X 22 is I or K, and X 23 is N or S, and X 24 is V or L, and X 25 is S or I, and X 26 is P or S, and X 27 is E or non-existent , X 28 is N or Y, and X 29 is K or R, and X30 is A or D, and X 31 is T or S, and X 32 is V or A, and X 33 is G or D, and X 34 is T, I, or S, and X 35 is T, S, or A), wherein optionally, the antibody The antibody or antigen-binding fragment thereof comprising the heavy chain or an antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 ( (ii) a second form of MUC16 (which is glycosylated and immunospecifically binds to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133); a second form of MUC16 is not glycosylated and lacks immunospecific binding to cells recombinantly expressing MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Cells recombinantly expressing the first form inhibit matrigel invasion in vitro.

[0106] In some embodiments, the heavy chain, or antigen-binding portion thereof, comprises the amino acid sequence of SEQ ID NO: 1. and a VH comprising the sequence, wherein optionally, the antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated and (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is non-glycosylated (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iv) inhibits matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16.

[0107] In some embodiments, the heavy chain or antigen-binding portion thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 21, wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is non-glycosylated wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion in vitro.

[0108] In some embodiments, the heavy chain or antigen-binding portion thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 41, wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is non-glycosylated wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion in vitro.

[0109] In some embodiments, the heavy chain or antigen-binding portion thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 61, wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is non-glycosylated wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion in vitro.

[0110] In some embodiments, the heavy chain or antigen-binding portion thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 81, wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is non-glycosylated wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion in vitro.

[0111] In certain embodiments, the antibody heavy chain, or antigen-binding portion thereof, comprises a human-derived heavy chain constant region. In certain embodiments, the heavy chain constant region comprises gamma 1, gamma 2, gamma 3, and gamma 4. In one embodiment, the antibody has an isotype selected from the group consisting of: The heavy chain is humanized. In certain embodiments, the antibody heavy chain is a humanized form of a rodent heavy chain.

[0112] Also provided herein is an antibody heavy chain conjugate comprising an antibody heavy chain provided herein, wherein the antibody heavy chain is conjugated to an agent. In certain embodiments, the agent is an imaging agent or a cytotoxic agent.

[0113] Among the antibodies and antigen-binding fragments thereof provided are those having a light chain and / or a portion thereof, e.g., a VL region thereof; such light chains and antigen-binding portions thereof are also provided. In some embodiments, the light chain or antigen-binding portion thereof comprises (a) the amino acid sequence [ka] (b) a VLCDR1 comprising the amino acid sequence column [ka] and (c) an amino acid sequence [ka] (wherein X6 is G or S, and X7 is H or Y), and optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof, wherein the antibody or antigen-binding fragment thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated, and wherein the first form is (ii) immunospecifically binds to cells recombinantly expressing a second form of MUC16, the amino acid sequence of which is SEQ ID NO: 133; (iii) immunospecifically binds to cells recombinantly expressing a second form of MUC16, the second form of which is non-glycosylated, (iii) lacks immunospecific binding to cells recombinantly expressing said first form of MUC16 (the amino acid sequence of said first form is SEQ ID NO: 139); and (iv) lacks immunospecific binding to cells recombinantly expressing said first form of MUC16 in vitro. Inhibits gel invasion.

[0114] In some embodiments, the light chain, or antigen-binding portion thereof, comprises: (a) the amino acid sequence [ka] (where X 11 is L or R, and X 12 is H or K); (b) an amino acid (c) a VLCDR2 comprising the sequence YMS (SEQ ID NO: 113); and (d) an amino acid sequence [ka] (where X 13 is G or S and X 14 is H or Y), wherein optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof comprises: (i) a first form of MUC16 (which first form is glycosylated, wherein the first form (ii) a second form of MUC16 (the amino acid sequence of which is SEQ ID NO: 133); (iii) a second form of MUC16 (which second form is non-glycosylated, wherein said second form is (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16 (the amino acid sequence of which is SEQ ID NO: 139); and (iv) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16 in vitro. Inhibits Rigel invasion.

[0115] In some embodiments, the light chain, or antigen-binding portion thereof, comprises: (a) the amino acid sequence [ka] (where X 19 is V or L, and X 20 is H or K); (b) an amino acid (c) VLCDR2 comprising the sequence YMS (SEQ ID NO: 119); and (d) the amino acid sequence [ka] wherein optionally, the antibody light chain or antigen-binding portion thereof comprises a VL comprising a VL CDR3 comprising The antibody or antigen-binding fragment thereof comprises: (i) a first form of MUC16, which first form is glycosylated; (ii) a second form of MUC16 (which second form is glycosylated), wherein the amino acid sequence of the first form is SEQ ID NO: 133; (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of cells in vitro.

[0116] In some embodiments, the light chain, or an antigen-binding portion thereof, comprises the amino acid sequence of SEQ ID NO: 6. VL CDR1 comprising the amino acid sequence of SEQ ID NO: 7, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 8 wherein optionally, the antibody light chain or antigen-binding portion thereof comprises a VL comprising a VLCDR3 comprising the sequence The antibody or antigen-binding fragment thereof, comprising the polypeptide, is characterized in that it binds to (i) a first form of MUC16 (wherein the first form is glycosylated). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and It inhibits matrigel invasion of expressing cells in vitro.

[0117] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 12, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 14. and a VL comprising a VLCDR3 comprising a VLQ sequence, wherein optionally, the antibody light chain or its antigen-binding The antibody or antigen-binding fragment thereof comprising the portion is capable of binding to (i) a first form of MUC16 (this first form is Glycine). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of expressing cells in vitro.

[0118] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 20. and a VL comprising a VLCDR3 comprising a VL CDR3 comprising a nucleotide sequence, wherein optionally, the antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of expressing cells in vitro.

[0119] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 28. and a VL comprising a VLCDR3 comprising a VLQ sequence, wherein optionally, the antibody light chain or its antigen-binding The antibody or antigen-binding fragment thereof comprising the portion is capable of binding to (i) a first form of MUC16 (this first form is Glycine). (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, which is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) lacks immunospecific binding to cells recombinantly expressing a second form of MUC16, which second form is unglycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion of expressing cells in vitro.

[0120] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 32, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 33, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 34. and a VL comprising a VLCDR3 comprising a VLQ sequence, wherein optionally, the antibody light chain or its antigen-binding The antibody or antigen-binding fragment thereof comprising the portion is capable of binding to (i) a first form of MUC16 (this first form is Glycine). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of expressing cells in vitro.

[0121] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 38, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 39, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 40. and a VL comprising a VLCDR3 comprising a VLQ sequence, wherein optionally, the antibody light chain or its antigen-binding The antibody or antigen-binding fragment thereof comprising the portion is capable of binding to (i) a first form of MUC16 (this first form is Glycine). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of expressing cells in vitro.

[0122] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 46, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 47, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 48. and a VL comprising a VLCDR3 comprising a VLQ sequence, wherein optionally, the antibody light chain or its antigen-binding The antibody or antigen-binding fragment thereof comprising the portion is capable of binding to (i) a first form of MUC16 (this first form is Glycine). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of expressing cells in vitro.

[0123] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 52, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 54. and a VL comprising a VLCDR3 comprising a VL CDR3 comprising a nucleotide sequence, wherein optionally, the antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of expressing cells in vitro.

[0124] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 58, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 60. and a VL comprising a VLCDR3 comprising a VLQ sequence, wherein optionally, the antibody light chain or its antigen-binding The antibody or antigen-binding fragment thereof comprising the portion is capable of binding to (i) a first form of MUC16 (this first form is Glycine). (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, which is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) lacks immunospecific binding to cells recombinantly expressing a second form of MUC16, which second form is unglycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion of expressing cells in vitro.

[0125] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 66, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 67, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 68. and a VL comprising a VLCDR3 comprising a VLQ sequence, wherein optionally, the antibody light chain or its antigen-binding The antibody or antigen-binding fragment thereof comprising the portion is capable of binding to (i) a first form of MUC16 (this first form is Glycine). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of expressing cells in vitro.

[0126] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 72, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 74. and a VL comprising a VLCDR3 comprising a VLQ sequence, wherein optionally, the antibody light chain or its antigen-binding The antibody or antigen-binding fragment thereof comprising the portion is capable of binding to (i) a first form of MUC16 (this first form is Glycine). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of expressing cells in vitro.

[0127] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 78, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 79, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 80. and a VL comprising a VLCDR3 comprising a VLQ sequence, wherein optionally, the antibody light chain or its antigen-binding The antibody or antigen-binding fragment thereof comprising the portion is capable of binding to (i) a first form of MUC16 (this first form is Glycine). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of expressing cells in vitro.

[0128] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 86, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 87, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 88. and a VL comprising a VLCDR3 comprising a VL CDR3 comprising a nucleotide sequence, wherein optionally, the antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion of expressing cells in vitro.

[0129] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 92, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 93, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 94. and a VL comprising a VLCDR3 comprising a VLQ sequence, wherein optionally, the antibody light chain or its antigen-binding The antibody or antigen-binding fragment thereof comprising the portion is capable of binding to (i) a first form of MUC16 (this first form is Glycine). (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, which is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) lacks immunospecific binding to cells recombinantly expressing a second form of MUC16, which second form is unglycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion of expressing cells in vitro.

[0130] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 98, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 99, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 100. and a VL comprising a VL CDR3 comprising the amino acid sequence The antibody or antigen-binding fragment thereof comprising the binding portion is capable of binding to (i) a first form of MUC16 (this first form is a group (ii) a second form of MUC16 (which is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion in vitro by cells expressing EGFR.

[0131] In some embodiments, the light chain, or antigen-binding portion thereof, [ka] (where X 36 is I or V, and X 37 is P or S, and X 38 is R or L, and X 39 is K or H, and X 40 is R or K, and X 41 is E or G, and X42 is S or G, and X 43 is Y or H), wherein optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is (ii) a first form of MUC16 that is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (this first form is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) a second form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing the second form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Cells recombinantly expressing one form of the compound inhibit matrigel invasion in vitro.

[0132] In some embodiments, the light chain, or an antigen-binding portion thereof, comprises the amino acid sequence of SEQ ID NO:2. and a VL comprising the sequence, wherein optionally, the antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated and (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is non-glycosylated wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion in vitro.

[0133] In some embodiments, the light chain or antigen-binding portion thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 22, wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is non-glycosylated wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion in vitro.

[0134] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL comprising the amino acid sequence of SEQ ID NO: 42, wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is non-glycosylated wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion in vitro.

[0135] In some embodiments, the light chain, or antigen-binding portion thereof, comprises a VL comprising the amino acid sequence of SEQ ID NO: 62, and optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is non-glycosylated wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion in vitro.

[0136] In some embodiments, the light chain or antigen-binding portion thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 82, and optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is non-glycosylated wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. Inhibits Matrigel invasion in vitro.

[0137] In some embodiments, the antibody light chain, or antigen-binding portion thereof, comprises a human-derived light chain constant region. In some embodiments, the light chain constant region has an isotype selected from the group consisting of kappa and lambda. In some embodiments, the antibody light chain is humanized. In some embodiments, the antibody light chain is a humanized form of a rodent antibody.

[0138] Also provided herein is an antibody light chain conjugate comprising an antibody light chain provided herein conjugated to an agent. In certain embodiments, the agent is an imaging agent or a cytotoxic agent.

[0139] Also provided herein is a fusion protein comprising an antibody light chain provided herein conjugated to an scFv via a peptide linker. In certain embodiments, the scFv binds to CD3.

[0140] Also provided herein are methods for producing one or more of the molecules provided herein, e.g., For example, a cell, e.g., an immune cell, e.g., a T cell, that recombinantly expresses a CAR provided herein.

[0141] Also provided herein is a polynucleotide comprising a nucleic acid sequence encoding an scFv provided herein. Also provided herein is a polynucleotide comprising a nucleic acid sequence encoding an scFv provided herein or a conjugate thereof. Also provided herein is a polynucleotide comprising a nucleic acid sequence encoding a CAR provided herein. Also provided herein is a polynucleotide comprising a nucleic acid sequence encoding the antibody heavy chain or antigen-binding portion thereof provided herein. Also provided herein is a polynucleotide comprising a nucleic acid sequence encoding the antibody heavy chain conjugate provided herein. Also provided herein is a polynucleotide comprising a nucleic acid sequence encoding the antibody light chain or antigen-binding portion thereof provided herein. Also provided herein is a polynucleotide comprising a nucleic acid sequence encoding the antibody light chain conjugate provided herein. Also provided herein is a polynucleotide comprising a nucleic acid sequence encoding the fusion protein provided herein. (a) A polynucleotide comprising a nucleic acid sequence encoding the antibody heavy chain or antigen-binding portion thereof provided herein. and (b) a polynucleotide comprising a nucleic acid sequence encoding an antibody heavy chain or antigen-binding portion thereof provided herein, an antibody light chain conjugate provided herein, or a fusion protein provided herein.

[0142] Also provided herein is a vector comprising a polynucleotide provided herein operably linked to a promoter. Also provided herein is a vector comprising: (a) a polynucleotide comprising: and (b) a first polynucleotide provided herein operably linked to one promoter; and (b) a second polynucleotide provided herein operably linked to a second promoter.

[0143] Also provided herein are ex vivo cells comprising a polynucleotide provided herein operably linked to a promoter. Also provided herein are ex vivo cells comprising a polynucleotide provided herein operably linked to a promoter. Also provided herein are ex vivo cells comprising a vector provided herein. Also provided herein are ex vivo cells comprising one or more polynucleotides encoding an antibody or antigen-binding fragment thereof provided herein operably linked to a promoter. The ex vivo cells contain a leukocyte.

[0144] Also provided herein is a method of producing an antibody heavy chain or antigen-binding portion thereof, comprising culturing a cell provided herein under conditions such that a polynucleotide is expressed by the cell to produce the antibody heavy chain or antigen-binding portion thereof, or antibody heavy chain conjugate encoded by the polynucleotide.

[0145] Also provided herein is a method of producing an antibody light chain or antigen-binding portion thereof, comprising culturing a cell provided herein under conditions such that a polynucleotide is expressed by the cell to produce the antibody light chain or antigen-binding portion thereof, antibody light chain conjugate, or fusion protein encoded by the polynucleotide.

[0146] Also provided herein is a method for producing an antibody or antigen-binding fragment thereof, comprising: culturing an ex vivo cell provided herein; and wherein a polynucleotide operably linked to a first promoter and a polynucleotide operably linked to a second promoter are expressed by the cell to produce (i) an antibody heavy chain or antibody fragment encoded by the polynucleotides. (ii) an antibody light chain encoded by the polynucleotide; and culturing under conditions to produce the light chain conjugate, or fusion protein.

[0147] Also provided herein are antibodies or antigen-binding fragments thereof provided herein, antibody conjugates provided herein, bispecific antibodies provided herein, bispecific antibody conjugates provided herein, scFvs, scFv conjugates provided herein, CARs provided herein, antibody heavy chains or antigens thereof provided herein, and antibodies or antigens thereof. A pharmaceutical composition comprising a therapeutically effective amount of a binding moiety, an antibody heavy chain conjugate provided herein, an antibody light chain or antigen-binding portion thereof provided herein, an antibody light chain conjugate provided herein, a fusion protein provided herein, or a T cell provided herein; and a pharmaceutically acceptable carrier.

[0148] Also provided herein is a method for treating cancer in a patient in need thereof, comprising administering to the patient a pharmaceutical composition provided herein. In some embodiments, the cancer is lung, pancreatic, breast, uterine, fallopian tube, or primary peritoneal cancer. In some embodiments, the cancer is ovarian cancer. In some embodiments, the patient is a human patient. In a specific embodiment, the method is a combination therapy further comprising administering to the patient a therapeutically effective amount of an additional therapeutic agent.

[0149] In a specific embodiment of the combination therapy, the pharmaceutical composition comprises a therapeutically effective amount of a first antibody that is an antibody or antigen-binding fragment thereof described herein, wherein the antibody or antigen-binding fragment thereof comprises N-glycosylation Asn1806 of SEQ ID NO: 150, but does not comprise N-glycosylation Asn1806 of SEQ ID NO: 150. In a specific embodiment, the additional therapeutic agent is a second antibody or antigen-binding fragment thereof that recognizes an epitope in MUC16 that does not include N-glycosylated Asn1800 of SEQ ID NO: 150, and wherein the second antibody or antigen-binding fragment thereof recognizes an epitope in MUC16 that includes N-glycosylated Asn1806 of SEQ ID NO: 150 and also includes N-glycosylated Asn1800 of SEQ ID NO: 150. The antigen-binding fragments include: (i) its ability to immunospecifically bind to a cell recombinantly expressing a first form of MUC16, which first form of MUC16 is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a third form of MUC16, which third form is glycosylated; (iii) its lack of immunospecific binding to cells recombinantly expressing a fourth form of MUC16, which is glycosylated, and wherein the amino acid sequence of the fourth form is SEQ ID NO: 139; and (iv) its lack of immunospecific binding to cells recombinantly expressing a fourth form of MUC16, which is glycosylated, and wherein the amino acid sequence of the fourth form is SEQ ID NO: 152. and wherein the antibody is identified by its ability to immunospecifically bind to cells recombinantly expressing the antibody, wherein the cell recombinantly expressing the first form of MUC16, the cell recombinantly expressing the third form of MUC16, and the cell recombinantly expressing the fourth form of MUC16 are of the same cell type; and The second antibody or antigen-binding fragment thereof comprises: (i) a first form of MUC16, which first form is glycosylated; and (ii) its ability to immunospecifically bind to cells recombinantly expressing a first form of MUC16 (the fifth form is cyclohexyl-2-methyl-1,3-diaminobenzyl-2,4 ... The fifth form is glycosylated, wherein the amino acid sequence of the fifth form is SEQ ID NO: 172. and wherein the antibody is identified by its lack of immunospecific binding to cells recombinantly expressing the antibody, and wherein the cells recombinantly expressing the first form of MUC16 are the same type of cells as the cells recombinantly expressing the fifth form of MUC16.

[0150] In a specific embodiment of the combination therapy, the pharmaceutical composition comprises a therapeutically effective amount of a first antibody or antigen-binding fragment thereof that is an antibody or antigen-binding fragment thereof described herein, wherein the antibody or antigen-binding fragment thereof recognizes an epitope in MUC16 that includes N-glycosylated Asn1806 of SEQ ID NO: 150, but does not include N-glycosylated Asn1800 of SEQ ID NO: 150, The additional therapeutic agent is a therapeutically effective amount of a second antibody or antigen-binding fragment thereof, wherein the second antibody or antigen-binding fragment thereof recognizes an epitope in MUC16 that includes N-glycosylated Asn1800 of SEQ ID NO: 150 but does not include N-glycosylated Asn1806 of SEQ ID NO: 150. In one embodiment, the first antibody or antigen-binding fragment thereof binds to (i) a first form of MUC16 (which The first form of MUC16 is glycosylated, wherein the amino acid sequence of the first form is (ii) its ability to immunospecifically bind to cells recombinantly expressing a third form of MUC16 (which third form is glycosylated, wherein the amino acid sequence of said third form is and (iii) its ability to immunospecifically bind to cells recombinantly expressing a fourth form of MUC16, which fourth form is glycosylated, wherein the amino acid sequence of the fourth form is SEQ ID NO: 152, wherein the cells recombinantly expressing the first form of MUC16, the cells recombinantly expressing the third form of MUC16, and the cells recombinantly expressing the fourth form of MUC16 are of the same cell type, and the second antibody or antigen-binding fragment thereof is identified by (i) its lack of immunospecific binding to cells recombinantly expressing a first form of MUC16, which first form is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 152; and (ii) its ability to immunospecifically bind to cells recombinantly expressing a third form of MUC16 (the amino acid sequence of which is SEQ ID NO: 133); (ii) its ability to immunospecifically bind to cells recombinantly expressing a third form of MUC16 (this third form of MUC16 is glycosylated, and wherein the amino acid sequence of the third form is SEQ ID NO: 139); and (iii) its ability to immunospecifically bind to cells recombinantly expressing a fourth form of MUC16 (the amino acid sequence of the fourth form is SEQ ID NO: 152). wherein the cell recombinantly expressing the first form of MUC16, the cell recombinantly expressing the third form of MUC16, and the cell recombinantly expressing the fourth form of MUC16 are of the same cell type.

[0151] Also provided herein are immunogenic glycopeptides comprising one or more glycosylation sites. wherein (i) the immunogenic glycopeptide is a peptide having 10 to 60 amino acid residues, 10 to 30 amino acid residues, and (ii) at least one of the one or more glycosylation sites is linked to a carbohydrate. In certain embodiments, the immunogenic glycopeptide has one, two, or three glycosylation sites. In certain embodiments, the immunogenic glycopeptide comprises a glycosylation site attached to a carbohydrate. In certain embodiments, the immunogenic glycopeptide comprises two glycosylation sites, each attached to a carbohydrate. In certain embodiments, the carbohydrate is , N- or O-linked carbohydrate. In certain embodiments, the carbohydrate is a monosaccharide, disaccharide, trisaccharide, tetrasaccharide, or pentasaccharide. In certain embodiments, the carbohydrate is a disaccharide. In certain embodiments, the disaccharide is chitobiose.

[0152] In certain embodiments, the N-terminus of the immunogenic glycopeptide is acetylated. In certain embodiments, the C-terminus of the glycopeptide is in the form of an N-methylcarboxamide derivative. In certain embodiments, the immunogenic glycopeptide is conjugated to an immunogenic carrier protein. In certain embodiments, the immunogenic carrier protein is keyhole limpet hemocyanin.

[0153] In certain embodiments, the immunogenic glycopeptide is 15 to 18 amino acid residues in length. In certain embodiments, the immunogenic glycopeptide comprises a glycosylation site linked to chitobiose. In certain embodiments, the immunogenic glycopeptide comprises two glycosylation sites, each linked to chitobiose.

[0154] In certain embodiments, the immunogenic glycopeptide is 18 amino acid residues in length. In certain embodiments, the immunogenic glycopeptide is composed of two glycopeptides, each of which is linked to chitobiose. Contains glycosylation sites.

[0155] In certain embodiments, the immunogenic glycopeptide is 15 amino acid residues in length. In certain embodiments, the immunogenic glycopeptide comprises a glycosylation site linked to chitobiose.

[0156] In certain embodiments, the immunogenic glycopeptide comprises at least one of the amino acid sequences of SEQ ID NO: 150. and at least a 10 amino acid portion, wherein at least one of the one or more glycosylation sites is in the portion of the amino acid sequence.

[0157] In certain embodiments, the immunogenic glycopeptide comprises the amino acid sequence of SEQ ID NO: 129. .

[0158] In certain embodiments, the immunogenic glycopeptide comprises a glycosylation site at residue 30 (Asn) of SEQ ID NO: 129 that is linked to chitobiose.

[0159] In certain embodiments, the immunogenic glycopeptide comprises a sequence linked to a Man3GlcNAc2 moiety. It contains a glycosylation site at residue 30 (Asn) of sequence 129.

[0160] In certain embodiments, the immunogenic glycopeptide comprises the amino acid sequence of SEQ ID NO: 130. In one embodiment, the immunogenic glycopeptide contains two glycosylation sites at residues 4 (Asn) and 10 (Asn) of SEQ ID NO: 130, each of which is linked to chitobiose. include.

[0161] In certain embodiments, the immunogenic glycopeptide comprises the amino acid sequence of SEQ ID NO: 131. In certain embodiments, the immunogenic glycopeptide comprises a glycosylation site at residue 7 (Asn) of SEQ ID NO: 131 that is linked to chitobiose.

[0162] Also provided herein are antibodies or peptides that specifically bind to glycol-proteins. A method for producing the antigen-binding fragment includes administering to a subject an immunoglobulin containing one or more glycosylation sites. immunizing the animal with an immunogenic glycopeptide, wherein (i) the immunogenic glycopeptide is 10 to 60 In one embodiment, the antibody is a glycopeptide having a length of 10 to 30 amino acid residues, 15 to 25 amino acid residues, 15 to 20 amino acid residues, or 15 to 18 amino acid residues, (ii) the immunogenic glycopeptide comprises at least a 10 amino acid portion of the amino acid sequence of the glycoprotein, (iii) at least one of the one or more glycosylation sites is linked to a carbohydrate, and (iv) at least one of the one or more glycosylation sites is in the portion of the amino acid sequence. Or the antigen-binding fragment thereof lacks specific binding to the non-glycosylated form of the glycoprotein. In some embodiments, the subject is a goat, sheep, donkey, chicken, guinea pig, rat, rabbit, or mouse. In some embodiments, the subject is a rat, rabbit, or mouse. In some embodiments, the subject is a mouse. In some embodiments, the immunogenic glycopeptide comprises one, two, or three glycosylation sites. The immunogen The method of any one of claims 190-195, wherein the immunogenic glycopeptide comprises a glycosylation site attached to a carbohydrate. In certain embodiments, the immunogenic glycopeptide comprises two glycosylation sites, each attached to a carbohydrate. In certain embodiments, the carbohydrate is an N- or O-linked carbohydrate. In certain embodiments, the carbohydrate is a monosaccharide, a disaccharide, a trisaccharide, or a saccharide. In certain embodiments, the carbohydrate is a disaccharide. In certain embodiments, the disaccharide is chitobiose. In certain embodiments, the N-terminus of the immunogenic glycopeptide is acetylated. In certain embodiments, the C-terminus of the glycopeptide is in the form of an N-methylcarboxamide derivative. In certain embodiments, the immunogenic glycopeptide is conjugated to an immunogenic carrier protein. In certain embodiments, the immunogenic carrier protein is keyhole limpet hemocyanin. In certain embodiments, the immunogenic glycopeptide is 15 to 18 amino acid residues in length. In certain embodiments, the immunogenic glycopeptide comprises a glycosylation site linked to chitobiose. In certain embodiments, the immunogenic glycopeptide comprises two glycosylation sites, each linked to a chitobiose. In certain embodiments, the immunogenic glycopeptide comprises The glycopeptide is 18 amino acid residues in length. In certain embodiments, the immunogenic glycopeptide comprises two glycosylation sites, each attached to a chitobiose. In one embodiment, the immunogenic glycopeptide is 15 amino acid residues in length. In one embodiment, the immunogenic glycopeptide comprises a glycosylation site linked to chitobiose. In one embodiment, the glycoprotein comprises the amino acid sequence of SEQ ID NO: 150. In one embodiment, the immunogenic glycopeptide comprises a glycosylation site linked to chitobiose. In one embodiment, the glycoprotein comprises the amino acid sequence of SEQ ID NO: 150. In one embodiment, the immunogenic glycopeptide comprises the amino acid sequence of SEQ ID NO: 129. wherein the immunogenic glycopeptide is a peptide comprising the 30th amino acid sequence of SEQ ID NO: 129 linked to chitobiose. In one embodiment, the immunogenic glycopeptide comprises a glycosylation site at residue (Asn). The glycidyl group at residue 30 (Asn) of SEQ ID NO: 129 is linked to a Man3GlcNAc2 moiety. In certain embodiments, the immunogenic glycopeptide comprises the amino acid sequence of SEQ ID NO: 130. In certain embodiments, the immunogenic glycopeptide comprises two cosylation sites at the 4th residue (Asn) and the 10th residue (Asn) of SEQ ID NO: 130, each of which is bound to chitobiose. In certain embodiments, the immunogenic glycopeptide comprises the amino acid sequence of SEQ ID NO: 131. In certain embodiments, the immunogenic glycopeptide comprises a chitobiotic It contains a glycosylation site at residue 7 (Asn) of SEQ ID NO: 131, which is bound to the ribosomal glycosylation site.

[0163] Also provided herein are antibodies that immunospecifically bind to MUC16 and their antigen binding Fragments having the VH, VL, VH CDR, and / or VL CDR sequences of an antibody described herein (e.g., 10C6, 7B12, 19C11, 16C5, or 18C6), as well as fragments thereof (e.g., conjugates (with anti-inflammatory or cytotoxic agents). The present invention provides, for example, the following items. (Item 1) An antibody or antigen-binding fragment thereof, the antibody comprising: (a) a first form of MUC16, which first form is glycosylated, wherein the first the amino acid sequence of which is SEQ ID NO: 133; (b) a second form of MUC16, which second form is not glycosylated, wherein the second the amino acid sequence of which is SEQ ID NO: 139; and (c) inhibiting matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16; The antibody or antigen-binding fragment thereof. (Item 2) 2. The antibody or antigen-binding fragment thereof of item 1, wherein the antibody lacks immunospecific binding to a cell recombinantly expressing a third form of MUC16, which third form is glycosylated, and wherein the amino acid sequence of the third form is SEQ ID NO: 139. (Item 3) An antibody or antigen-binding fragment thereof, the antibody comprising: (a) a first form of MUC16, which first form is glycosylated, wherein the first the amino acid sequence of which is SEQ ID NO: 133; (b) a third form of MUC16, which third form is glycosylated, wherein the third the amino acid sequence of which is SEQ ID NO: 139; and (c) inhibiting matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16; the antibody or antigen-binding fragment thereof, (i) the cell recombinantly expressing said first form of MUC16 is a SKOV3 cell; and (ii) the cell recombinantly expressing said first form of MUC16 is a SKOV3 cell. 2. The antibody or antigen-binding fragment thereof of item 1, wherein (iii) the cell recombinantly expressing the second form is a SKOV3 cell; and (iii) the cell in step (c) is a SKOV3 cell. (Item 4) (i) the cell recombinantly expressing said first form of MUC16 is a SKOV3 cell; and (ii) the cell recombinantly expressing said first form of MUC16 is a SKOV3 cell. (iii) the cells recombinantly expressing the third form are SKOV3 cells; and (iii) the cells in step (c) are SKOV3 4. The antibody or antigen-binding fragment thereof according to item 3, which is a cell. (Item 5) (i) the cell recombinantly expressing said first form of MUC16 is a SKOV3 cell; and (ii) the cell recombinantly expressing said first form of MUC16 is a SKOV3 cell. 3. The antibody or antigen-binding fragment thereof of item 2, wherein (iii) the cell recombinantly expressing the second form is a SKOV3 cell; (iv) the cell recombinantly expressing the third form of MUC16 is a SKOV3 cell; and (iv) the cell in step (c) is a SKOV3 cell. (Item 6) the antibody or antigen-binding fragment thereof having the amino acid sequence [ka] immunospecifically binds to [ka] 6. The antibody or antigen-binding fragment thereof according to any one of items 1 to 5, wherein amino acid residue 4 (N4) and amino acid residue 10 (N10) are glycosylated. (Item 7) The antibody or antigen-binding fragment thereof comprises N-glycosylated asparagine 1806 of SEQ ID NO: 150. 7. The antibody or antigen-binding fragment thereof according to any one of items 1 to 6, which immunospecifically binds to an epitope comprising (Item 8) the antibody or antigen-binding fragment thereof having the amino acid sequence [ka] immunospecifically binds to [ka] 8. The antibody according to any one of items 1 to 7, wherein amino acid residue number 7 (N7) of or an antigen-binding fragment thereof. (Item 9) 9. The antibody or antigen-binding fragment thereof according to any one of items 6 to 8, wherein the glycosylation consists of N-linked chitobiose. (Item 10) The antibody or antigen-binding fragment thereof is used to induce cell proliferation and differentiation of cells expressing the first form of MUC16. 10. The antibody or antigen-binding fragment thereof according to any one of items 1 to 9, which is internalized into a cell when contacted with the antigen-binding fragment. (Item 11) 11. The antibody or antigen-binding fragment thereof of item 10, wherein the cell is a SKOV3 cell recombinantly expressing the first form of MUC16. (Item 12) 12. The antibody or antigen-binding fragment thereof of any one of items 1 to 11, wherein the antibody inhibits the growth of tumors expressing a glycosylated form of MUC16. (Item 13) 13. The antibody or its derivative according to any one of items 1 to 12, wherein the antibody is a monoclonal antibody. Antigen-binding fragment. (Item 14) the antibody or antigen-binding fragment thereof (a) Amino acid sequence [ka] (wherein X1 is L or V); (b) Amino acid sequence [ka] wherein X2 is E or absent and X3 is Y or N; and (c) Amino acid sequence [ka] VHCDR3 containing 14. The antibody or antigen-binding domain thereof according to any one of items 1 to 13, comprising a heavy chain variable region (VH) comprising: Combined piece. (Item 15) the antibody or antigen-binding fragment thereof (a) Amino acid sequence [ka] (wherein X8 is N or S and X9 is L or V); (b) Amino acid sequence [ka] (where X 10 is E or absent); and (c) Amino acid sequence [ka] VH CDR3 comprising 14. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13, comprising a VH comprising: (Item 16) the antibody or antigen-binding fragment thereof (a) Amino acid sequence [ka] (where X 15 is N or S, and X 16 VHCDR1 comprising: (b) Amino acid sequence [ka] (where X 17 is E or absent); and (c) Amino acid sequence [ka] (where X 18 is T, A, or S) 14. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13, comprising a VH comprising: (Item 17) the antibody or antigen-binding fragment thereof comprises a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 5; 15. The antibody or antigen-binding fragment thereof according to any one of items 1 to 14, (Item 18) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 9, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 11; 16. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13 or 15, comprising: (Item 19) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15; 17. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13 or 16, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 17. (Item 20) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 23; 15. The antibody or antigen-binding fragment thereof according to any one of items 1 to 14, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 25. (Item 21) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 29; 16. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13 or 15, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 31. (Item 22) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 35; 17. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13 or 16, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 37. (Item 23) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 43; 15. The antibody or antigen-binding fragment thereof according to any one of items 1 to 14, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 45. (Item 24) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 49; 16. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13 or 15, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 51. (Item 25) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 55; 17. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13 or 16, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 57. (Item 26) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 63; 15. The antibody or antigen-binding fragment thereof according to any one of items 1 to 14, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 65. (Item 27) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 69; 16. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13 or 15, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 71. (Item 28) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 75; 17. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13 or 16, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 76, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 77. (Item 29) the antibody comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 83, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 84, 15. The antibody or antigen-binding fragment thereof according to any one of items 1 to 14, comprising a VH comprising a VH CDR2 comprising the VH CDR2 of the VH CDR2 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 85. (Item 30) the antibody or antigen-binding fragment thereof comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 89; 16. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13 or 15, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 90, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 91. (Item 31) the antibody or antigen-binding fragment thereof comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 95; 17. The antibody or antigen-binding fragment thereof according to any one of items 1 to 13 or 16, comprising a VH comprising a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 97. (Item 32) the antibody or antigen-binding fragment thereof [ka] (where X 21 is T or N, and X 22 is I or K, and X 23 is N or S, and X 24 is V or L, and X 25 is S or I, and X 26 is P or S, and X 27 is E or non-existent , X 28 is N or Y, and X29 is K or R, and X 30 is A or D, and X 31 is T or S, and X 32 is V or A, and X 33 is G or D, and X 34 is T, I, or S, and X 35 32. The antibody or antigen-binding fragment thereof according to any one of items 1 to 31, comprising a VH comprising the amino acid sequence: (Item 33) 33. The antibody or antigen-binding fragment thereof according to any one of items 1 to 19 or 32, wherein the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 1. (Item 34) Item 1. The antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 21. The antibody or antigen-binding fragment thereof according to any one of claims 16 to 32. (Item 35) Item 1, wherein the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 41. 33. The antibody or antigen-binding fragment thereof according to any one of claims 16 to 32. (Item 36) Item 1. The antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 61. 33. The antibody or antigen-binding fragment thereof according to any one of claims 16 to 32. (Item 37) Item 1. The antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 81. The antibody or antigen-binding fragment thereof according to any one of claims 16 to 32 or 29 to 32. (Item 38) the antibody or antigen-binding fragment thereof (a) Amino acid sequence [ka] (wherein X4 is R or L and X5 is K or H); (b) Amino acid sequence [ka] a VL CDR2 comprising: (c) Amino acid sequence [ka] (wherein X6 is G or S and X7 is H or Y) 38. The antibody or antigen-binding domain thereof according to any one of items 1 to 37, comprising a light chain variable region (VL) comprising: Combined piece. (Item 39) the antibody or antigen-binding fragment thereof (a) Amino acid sequence [ka] (where X 11 is L or R, and X 12 is H or K); (b) a VL CDR2 comprising the amino acid sequence YMS (SEQ ID NO: 113); and (c) Amino acid sequence [ka] (where X 13 is G or S and X 14 is H or Y) 38. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37, comprising a VL comprising: (Item 40) the antibody or antigen-binding fragment thereof (a) Amino acid sequence [ka] (where X 19 is V or L, and X 20is H or K); (b) a VL CDR2 comprising the amino acid sequence YMS (SEQ ID NO: 119); and (c) Amino acid sequence [ka] VL CDR3 containing 38. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37, comprising a VL comprising: (Item 41) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 26; and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 28. 39. The antibody or antigen-binding fragment thereof according to any one of items 1 to 38, comprising a light chain variable region (VL). . (Item 42) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 32; and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 33, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 34. 40. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37 or 39, comprising: (Item 43) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 38; and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 39, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 40. 41. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37 or 40, comprising: (Item 44) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 46; and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 47, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 48. 39. The antibody or antigen-binding fragment thereof according to any one of items 1 to 38, comprising a light chain variable region (VL). . (Item 45) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 52; VLCDR2 comprising the amino acid sequence of SEQ ID NO: 53, and VLCDR3 comprising the amino acid sequence of SEQ ID NO: 54. 40. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37 or 39, comprising: (Item 46) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 58; and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 60. 41. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37 or 40, comprising: (Item 47) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 86; and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 87, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 88. 39. The antibody or antigen-binding fragment thereof according to any one of items 1 to 38, comprising a light chain variable region (VL). . (Item 48) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 92; and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 93, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 94. 40. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37 or 39, comprising: (Item 49) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 98; 41. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37 or 40, comprising a VL comprising a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 99, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 100. (Item 50) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 6, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 8. 38. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37, comprising a chain variable region (VL). (Item 51) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 12; and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 14. 38. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37, comprising: (Item 52) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 18; and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 20. 38. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37, comprising: (Item 53) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 66; and a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 67, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 68. 38. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37, comprising a light chain variable region (VL). . (Item 54) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 72; VL CDR2 comprising the amino acid sequence of SEQ ID NO: 73, and VL CDR3 comprising the amino acid sequence of SEQ ID NO: 74. 38. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37, comprising: (Item 55) the antibody or antigen-binding fragment thereof comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 78; VL CDR2 comprising the amino acid sequence of SEQ ID NO:79, and VL CDR3 comprising the amino acid sequence of SEQ ID NO:80. 38. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37, comprising: (Item 56) the antibody or antigen-binding fragment thereof [ka] (where X 36 is I or V, and X 37 is P or S, and X 38 is R or L, and X 39 is K or H, and X 40 is R or K, and X 41 is E or G, and X 42 is S or G, and X 43 50. The method according to any one of items 1 to 49, comprising a VL comprising an amino acid sequence of The antibody or antigen-binding fragment thereof described above. (Item 57) Item 1, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 22. 44. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 43. (Item 58) Item 1, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 42. 47. The antibody or antigen-binding fragment thereof according to any one of claims 40 to 46, or 44 to 46. (Item 59) Item 1. The antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 82. 49. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 40, or 47 to 49. (Item 60) 53. The antibody or antigen-binding fragment thereof according to any one of items 1 to 37 or 50 to 52, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 2. (Item 61) Item 1, wherein the antibody or antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO: 62. 56. The antibody or antigen-binding fragment thereof according to any one of claims 37 to 55, or 53 to 55. (Item 62) An antibody or antigen-binding fragment thereof that immunospecifically binds to MUC16, The original binding fragment comprises a VH, wherein the VH is: (a) Amino acid sequence [ka] wherein X1 is L or V; [ka] wherein X2 is E or absent and X3 is Y or N; and amino acid sequence [ka] a VH CDR3 comprising: (b) Amino acid sequence [ka] wherein X8 is N or S and X9 is L or V; Acid sequence [ka] (where X 10 is E or absent); and [ka] a VH CDR3 comprising: (c) Amino acid sequence [ka] (where X 15 is N or S and X 16 VHCDR1 containing the amino acid sequence (V or L); Acid sequence [ka] (where X 17 is E or absent); and [ka] (where X 18 is T, A, or S; or (d) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 5; or (e) VH CDR1 comprising the amino acid sequence of SEQ ID NO: 9, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 10 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 11; or (f) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 17; or (g) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 25; or (h) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 29, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 31; or (i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 35, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 37; or (j) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 43, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 45; or (k) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 49, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 51; or (l) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 55, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 57; or (m) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 63, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 65; or (n) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 69, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 71; or (o) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 75, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 76, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 77; or (p) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 83, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 84, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 85; or (q) VHCDR1 comprising the amino acid sequence of SEQ ID NO: 89, VHCDR2 comprising the amino acid sequence of SEQ ID NO: 90 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 91; or (r) VH CDR1 comprising the amino acid sequence of SEQ ID NO: 95, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and VH CDR3 comprising the amino acid sequence of SEQ ID NO: 97 The antibody or antigen-binding fragment thereof that immunospecifically binds to MUC16, comprising: (Item 63) An antibody or antigen-binding fragment thereof that immunospecifically binds to MUC16, The original binding fragment comprises a VL, wherein the VL is: (a) Amino acid sequence [ka] wherein X4 is R or L and X5 is K or H; Acid sequence [ka] and a VL CDR2 comprising the amino acid sequence [ka] wherein X6 is G or S and X7 is H or Y; or (b) Amino acid sequence [ka] (where X 11 is L or R and X 12 VLCDR1 containing the amino acid sequence (H or K); VL CDR2 containing the amino acid sequence YMS (SEQ ID NO: 113); and the amino acid sequence [ka] (where X 13 is G or S and X 14 is H or Y; or (c) Amino acid sequence [ka] (where X 19 is V or L, and X 20VLCDR1 containing the amino acid sequence (H or K); VL CDR2 containing the amino acid sequence YMS (SEQ ID NO: 119); and the amino acid sequence [ka] a VL CDR3 comprising: (d) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 28; or (e) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 32, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 33, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 34; or (f) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 38, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 39, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 40; or (g) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 46, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 47, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 48; or (h) VLCDR1 comprising the amino acid sequence of SEQ ID NO: 52, VLCDR2 comprising the amino acid sequence of SEQ ID NO: 53 and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 54; or (i) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 58, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 60; or (j) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 86, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 87, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 88; or (k) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 92, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 93, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 94; or (l) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 98, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 99, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 100; or (m) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 6, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 8; or (n) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 12, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 14; or (o) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 20; or (p) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 66, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 67, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 68; or (q) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 72, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 74; or (r) VL CDR1 comprising the amino acid sequence of SEQ ID NO: 78, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 79, and VL CDR3 comprising the amino acid sequence of SEQ ID NO: 80 The antibody or antigen-binding fragment thereof that immunospecifically binds to MUC16, comprising: (Item 64) An antibody or antigen-binding fragment thereof that immunospecifically binds to MUC16, The original combined fragments are: (a)(i) Amino acid sequence [ka] wherein X1 is L or V; [ka] wherein X2 is E or absent and X3 is Y or N; and amino acid sequence [ka] and (ii) a VH comprising a VH CDR3 comprising the amino acid sequence [ka] wherein X4 is R or L and X5 is K or H; Acid sequence [ka] and a VLCDR2 comprising the amino acid sequence [ka] (wherein X6 is G or S and X7 is H or Y) VL comprising: (b)(i) Amino acid sequence [ka] wherein X8 is N or S and X9 is L or V; Acid sequence [ka] (where X 10 is E or absent); and [ka] VH CDR3 comprising and (ii) a VH comprising the amino acid sequence [ka] (where X 11 is L or R and X12 VLCDR1 containing the amino acid sequence (H or K); VLCDR2 containing the amino acid sequence YMS (SEQ ID NO: 113); and the amino acid sequence [ka] (where X 13 is G or S and X 14 is H or Y; or (c)(i) Amino acid sequence [ka] (where X 15 is N or S and X 16 VHCDR1 containing the amino acid sequence (V or L); Acid sequence [ka] (where X 17 is E or absent); and [ka] (where X 18 is T, A, or S); and (ii) a VHCDR3 comprising the amino acid sequence [ka] (where X 19 is V or L, and X 20 VLCDR1 containing the amino acid sequence (H or K); VL CDR2 containing the amino acid sequence YMS (SEQ ID NO: 119); and the amino acid sequence [ka] VL CDR3 containing VL comprising: (d) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 26 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 27, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 28 a VL comprising a VL CDR3 comprising the amino acid sequence; or (e) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 29, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 31; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 32. a VL comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 33, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 33, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 34; or (f) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 35, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 38. VL CDR1 comprising the amino acid sequence of SEQ ID NO: 39, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 40, a VL comprising a VL CDR3 comprising the amino acid sequence; or (g) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 43, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 45; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 46 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 47, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 48 a VL comprising a VL CDR3 comprising the amino acid sequence; or (h) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 49, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 51; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 52. VL CDR1 comprising the amino acid sequence of SEQ ID NO: 53, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 54 a VL comprising a VL CDR3 comprising the amino acid sequence; or (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 55, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 57; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 58 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 59, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 60 a VL comprising a VL CDR3 comprising the amino acid sequence; or (j) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 83, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 84, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 85; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 86 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 87, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 88 a VL comprising a VL CDR3 comprising the amino acid sequence; or (k) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 89, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 90, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 91; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 92. VL CDR1 comprising the amino acid sequence of SEQ ID NO: 93, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 94 a VL comprising a VL CDR3 comprising the amino acid sequence; or (l) (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 95, a VH CDR2 having the amino acid sequence of SEQ ID NO: 96, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 97, and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 98, a VL CDR2 having the amino acid sequence of SEQ ID NO: 99, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 100. a VL comprising a VL CDR3 comprising the amino acid sequence; or (m) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 5; and (ii) an amino acid sequence of SEQ ID NO: 6 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 7, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 8 a VL comprising a VL CDR3 comprising the sequence; or (n) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 9, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 11; and (ii) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 12, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 14. a VL comprising a VL CDR3 comprising the amino acid sequence; or (o) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 17; and (ii) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 18. VL CDR1 comprising the amino acid sequence of SEQ ID NO: 19, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 20 a VL comprising a VL CDR3 comprising the amino acid sequence; or (p) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 63, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 65; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 66 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 67, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 68 a VL comprising a VL CDR3 comprising the amino acid sequence; or (q) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 69, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 71; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 72. VL CDR1 comprising the amino acid sequence of SEQ ID NO: 73, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 74 a VL comprising a VL CDR3 comprising the amino acid sequence; or (r) (i) a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 75, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 76, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 77; and (ii) a VH comprising the amino acid sequence of SEQ ID NO: 78 VL CDR1 comprising the amino acid sequence of SEQ ID NO: 79, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 80 VL containing amino acid sequence VL containing CDR3 The antibody or antigen-binding fragment thereof that immunospecifically binds to MUC16, comprising: (Item 65) An antibody or antigen-binding fragment thereof that immunospecifically binds to MUC16, The original combined fragments are: (a)(i) [ka] (where X 21 is T or N, and X 22 is I or K, and X 23 is N or S, and X 24 is V or L, and X 25 is S or I, and X 26 is P or S, and X 27 is E or non-existent, and X 28 is N or Y, and X 29 is K or R, and X 30 is A or D, and X 31 is T or S, and X 32 is V or A, and X 33 teeth , G or D, and X 34 is T, I, or S, and X 35 is T, S, or A); and (ii) a VH comprising the amino acid sequence [ka] (where X36 is I or V, and X 37 is P or S, and X 38 is R or L, and X 39 is K or H, and X 40 is R or K, and X 41 is E or G, and X 42 is S or G and X 43 VL comprising the amino acid sequence or (b) (i) a VH comprising the amino acid sequence of SEQ ID NO: 1; and (ii) a VL comprising the amino acid sequence of SEQ ID NO: 2; (c) (i) a VH comprising the amino acid sequence of SEQ ID NO: 21; and (ii) a VL comprising the amino acid sequence of SEQ ID NO: 22; or (d) (i) a VH comprising the amino acid sequence of SEQ ID NO: 41; and (ii) a VL comprising the amino acid sequence of SEQ ID NO: 42; or (e) (i) a VH comprising the amino acid sequence of SEQ ID NO: 61; and (ii) a VL comprising the amino acid sequence of SEQ ID NO: 62; or (f) (i) a VH comprising the amino acid sequence of SEQ ID NO: 81; and (ii) a VL comprising the amino acid sequence of SEQ ID NO: 82. The antibody or antigen-binding fragment thereof that immunospecifically binds to MUC16, comprising: (Item 66) 66. The antibody or antigen-binding fragment thereof according to any one of items 14 to 65, wherein the antibody comprises human-derived heavy and light chain constant regions. (Item 67) 67. The antibody or antigen-binding fragment thereof according to item 66, wherein the heavy chain constant region has an isotype selected from the group consisting of gamma 1, gamma 2, gamma 3, and gamma 4. (Item 68) 68. The antibody or antigen-binding fragment thereof according to item 66 or 67, wherein the light chain constant region has an isotype selected from the group consisting of kappa and lambda. (Item 69)

[0023] Items 1 to 31, 38 to 55, or 62 to 64, wherein the antibody or antigen-binding fragment thereof is humanized. The antibody or antigen-binding fragment thereof described in any one of the above. (Item 70) 70. The antibody or antigen-binding fragment thereof of item 69, wherein the antibody or antigen-binding fragment thereof is a humanized form of a rodent antibody. (Item 71) 71. The antibody or antigen-binding fragment thereof according to any one of items 1 to 70, wherein the antibody is an immunoglobulin comprising two identical heavy chains and two identical light chains. (Item 72) 72. The antibody or antigen-binding fragment thereof of item 71, wherein the immunoglobulin is an IgG. (Item 73) 73. The antibody or antigen thereof according to any one of items 1 to 72, conjugated to a drug. Antibody conjugates containing binding fragments. (Item 74) 74. The antibody conjugate of item 73, wherein the agent is an imaging agent or a cytotoxic agent. (Item 75) 71. The method according to any one of items 1 to 70, wherein the antibody or antigen-binding fragment thereof is a bispecific antibody. The antibody or antigen-binding fragment thereof described above. (Item 76) 76. The bispecific antibody of paragraph 75, wherein the bispecific antibody immunospecifically binds to CD3. (Item 77) the bispecific antibody comprises an immunoglobulin that immunospecifically binds to MUC16, The light chain of the immunoglobulin immunospecifically binds to CD3 via a peptide linker. Item 78. The bispecific antibody according to Item 75 or 76, which is conjugated to a single-chain variable fragment (scFv). 78. A bispecific antibody conjugate comprising the bispecific antibody of any one of items 75 to 77 conjugated to a drug. (Item 79) 79. The bispecific antibody conjugate of item 78, wherein the agent is an imaging agent or a cytotoxic agent. (Item 80) 71. The antibody or its antigen-binding fragment according to any one of items 1 to 70, wherein the antigen-binding fragment is an scFv. Original combined fragment. (Item 81) 81. An scFv conjugate comprising the scFv of item 80 conjugated to a drug. (Item 82) 82. The scFv conjugate of item 81, wherein the agent is an imaging agent or a cytotoxic agent. (Item 83) A chimeric antigen receptor (CAR) comprising the antibody or antigen-binding fragment according to any one of items 1 to 72; or the scFv according to item 80 or the scFv conjugate according to item 81 or 82. (Item 84) 1. An antibody heavy chain, or antigen-binding portion thereof, comprising a VH, wherein the VH comprises: (I)(a) Amino acid sequence [ka] (wherein X1 is L or V); (b) Amino acid sequence [ka] wherein X2 is E or absent and X3 is Y or N; and (c) Amino acid sequence [ka] wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof comprises: (i) a first form of MUC16, which first form is glycosylated and (ii) a second form of MUC16, which is unglycosylated; (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion in vitro; or (II)(a) Amino acid sequence [ka] wherein X8 is N or S and X9 is L or V; (b) Amino acid sequence [ka] (where X 10 is E or absent); and (c) Amino acid sequence [ka] wherein, optionally, an antibody or antibody comprising said antibody heavy chain or antigen-binding portion thereof The antigen-binding fragment comprises: (i) a first form of MUC16 (which first form is glycosylated and (ii) a second form of MUC16, which is unglycosylated; (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and Inhibits Matrigel invasion in vitro; or (III)(a) Amino acid sequence [ka] (where X15 is N or S and X 16 VHCDR1 containing (wherein V is V or L); (b) Amino acid sequence [ka] (where X 17 is E or absent); and (c) Amino acid sequence [ka] (where X 18 is T, A, or S); or an antibody or antigen-binding fragment thereof comprising an antigen-binding portion thereof, comprising: (i) a first form of MUC16, which first form is glycosylated, and wherein the amino acid sequence of the first form is (ii) immunospecifically binds to cells recombinantly expressing a second form of MUC16 ( the second form is not glycosylated and lacks immunospecific binding to cells recombinantly expressing MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibiting matrigel invasion in vitro of cells recombinantly expressing said first form of; or (IV) VH CDR1 comprising the amino acid sequence of SEQ ID NO: 3, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 5 (wherein, optionally, the antibody heavy chain or The antibody or antigen-binding fragment thereof comprising the antigen-binding portion is (i) a first form of MUC16 (this first form is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133 (ii) a second form of MUC16, which is non-glycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139; (iii) inhibits Matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16; or (V) VH CDR1 comprising the amino acid sequence of SEQ ID NO: 9, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 11, wherein optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133 (ii) a second form of MUC16, which is non-glycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139; (iii) inhibits Matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16; or (VI) VH CDR1 comprising the amino acid sequence of SEQ ID NO: 15, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 16 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 17 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (VII) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 25 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form) (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (VIII) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 29, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 31 (optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this (ii) a first form of MUC16 that is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (this first form is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) a second form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing the second form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing one form of or (IX) VH CDR1 comprising the amino acid sequence of SEQ ID NO: 35, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 36 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 37 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (X) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 43, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 44, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 45, wherein optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133 (ii) a second form of MUC16, which is non-glycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139; (iii) inhibits Matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16; or (XI) VH CDR1 comprising the amino acid sequence of SEQ ID NO: 49, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 50 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 51 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (XII) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 55, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 57, wherein optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form) (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (XIII) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 63, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 65 (wherein, optionally, the antibody heavy chain or The antibody or antigen-binding fragment thereof comprising the antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this (ii) a first form of MUC16 that is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (this first form is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133); (ii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the second form is non-glycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) inhibits matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16; or (XIV) A VH CDR1 comprising the amino acid sequence of SEQ ID NO: 69, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 71 (optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form) (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (XV) VH CDR1 comprising the amino acid sequence of SEQ ID NO: 75, VH CDR2 comprising the amino acid sequence of SEQ ID NO: 76 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 77 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (XVI) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 83, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 84, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 85, wherein optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (XVII) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 89, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 90, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 91 (wherein, optionally, the antibody heavy chain or The antibody or antigen-binding fragment thereof comprising the antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this (ii) a first form of MUC16 that is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (this first form is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) a second form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing the second form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibiting matrigel invasion in vitro of cells recombinantly expressing one form of (XVIII) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 95, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 96, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 97 (wherein, optionally, the antibody heavy chain or The antibody or antigen-binding fragment thereof comprising the antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this (ii) a first form of MUC16 that is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (this first form is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) a second form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing the second form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits matrigel invasion in vitro of cells recombinantly expressing one form of The antibody heavy chain or antigen-binding portion thereof comprising: (Item 85) 1. An antibody heavy chain or antigen-binding portion thereof, wherein the heavy chain or antigen-binding portion thereof: (I) [ka] (where X 21 is T or N, and X 22 is I or K, and X 23 is N or S, and X 24 is V or L, and X 25 is S or I, and X 26 is P or S, and X 27 is E or non-existent, and X 28 is N or Y, and X 29 is K or R, and X 30 is A or D, and X 31 is T or S, and X 32 is V or A, and X 33 teeth , G or D, and X 34 is T, I, or S, and X 35 is T, S, or A), wherein optionally, the antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16 (which first form is glycosylated), (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16, wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) a second form of MUC16, which second form is glycosylated (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits cell invasion of Matrigel in vitro); or (II) the amino acid sequence of SEQ ID NO: 1, wherein, optionally, the antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated; (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits matrigel invasion of expressing cells in vitro); or (III) the amino acid sequence of SEQ ID NO: 21, wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16 (this first form is Glycine); (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion of expressing cells in vitro); or (IV) the amino acid sequence of SEQ ID NO: 41, optionally comprising the antibody heavy chain or antigen-binding portion thereof The antibody or antigen-binding fragment thereof comprises: (i) a first form of MUC16 (this first form is Glycine); (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion of expressing cells in vitro); or (V) the amino acid sequence of SEQ ID NO: 61, wherein optionally, an antibody or antigen-binding fragment thereof comprising the antibody heavy chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iv) inhibits matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16; or (VI) the amino acid sequence of SEQ ID NO: 81, wherein optionally, the antibody heavy chain or antigen-binding portion thereof The antibody or antigen-binding fragment thereof comprises: (i) a first form of MUC16 (this first form is Glycine); (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro by cells expressing The antibody heavy chain or antigen-binding portion thereof, comprising a VH comprising: (Item 86) 86. The antibody heavy chain or antigen-binding portion thereof according to item 84 or 85, wherein the antibody heavy chain or antigen-binding portion thereof comprises a human-derived heavy chain constant region. (Item 87) The constant region of the heavy chain or antigen-binding portion thereof is selected from gamma 1, gamma 2, gamma 3, and gamma 4. 87. The antibody heavy chain according to item 86, having an isotype selected from the group consisting of mAb, ... Original connective part. (Item 88) 86. The antibody heavy chain or antigen-binding portion thereof of item 85, wherein the antibody heavy chain or antigen-binding portion thereof is humanized. (Item 89) 89. The antibody heavy chain or antigen-binding portion thereof of item 88, wherein the antibody heavy chain or antigen-binding portion thereof is a humanized form of a rodent heavy chain. (Item 90) 90. An antibody heavy chain conjugate comprising the antibody heavy chain or antigen-binding portion thereof according to any one of items 84 to 89, wherein the antibody heavy chain or antigen-binding portion thereof is conjugated to a drug. (Item 91) 91. The antibody heavy chain conjugate of item 90, wherein the agent is an imaging agent or a cytotoxic agent. (Item 92) 1. An antibody light chain, or an antigen-binding portion thereof, comprising: (I)(a) Amino acid sequence [ka] (wherein X4 is R or L and X5 is K or H); (b) Amino acid sequence [ka] a VL CDR2 comprising: (c) Amino acid sequence [ka] (wherein X6 is G or S and X7 is H or Y) and optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof, wherein the antibody or antigen-binding fragment thereof comprises: (i) a first form of MUC16, which first form is glycosylated, wherein the first (ii) a second form of MUC16 (the amino acid sequence of which is SEQ ID NO: 133); (iii) a second form of MUC16 (which second form is non-glycosylated, wherein said second form is (iii) lacking immunospecific binding to cells recombinantly expressing said first form of MUC16 (the amino acid sequence of which is SEQ ID NO: 139); and (iv) lacking immunospecific binding to cells recombinantly expressing said first form of MUC16 in vitro matrigel plating. inhibits le invasion); or (II)(a) Amino acid sequence [ka] (where X 11 is L or R and X 12 is H or K); (b) a VL CDR2 comprising the amino acid sequence YMS (SEQ ID NO: 113); and (c) Amino acid sequence [ka] (where X 13 is G or S and X 14 is H or Y) and optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof, comprising: (i) a first form of MUC16, which first form is glycosylated, wherein the first (ii) immunospecifically binds to cells recombinantly expressing a second form of MUC16, the amino acid sequence of which is SEQ ID NO: 133; (iii) immunospecifically binds to cells recombinantly expressing a second form of MUC16, the second form of which is non-glycosylated, (iii) lacks immunospecific binding to cells recombinantly expressing said first form of MUC16 (the amino acid sequence of said first form is SEQ ID NO: 139); and (iv) lacks immunospecific binding to cells recombinantly expressing said first form of MUC16 in vitro. inhibits gel invasion); or (III)(a) Amino acid sequence [ka] (where X 19 is V or L, and X 20 is H or K); (b) a VL CDR2 comprising the amino acid sequence YMS (SEQ ID NO: 119); and (c) Amino acid sequence [ka] and a VL CDR3 comprising: (ii) a second form of MUC16, which is unglycosylated; (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro); or (IV) VL CDR1 comprising the amino acid sequence of SEQ ID NO: 6, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 8 (wherein, optionally, the antibody light chain or The antibody or antigen-binding fragment thereof comprising the antigen-binding portion is (i) a first form of MUC16 (this first form is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133 (ii) a second form of MUC16, which is non-glycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139; (iii) inhibits Matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16; or (V) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 12, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 14, wherein optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16 (this first form is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133 (ii) a second form of MUC16, which is non-glycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139; (iii) inhibits Matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16; or (VI) VL CDR1 comprising the amino acid sequence of SEQ ID NO: 18, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 19 and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 20 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (VII) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 28 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form) (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (VIII) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 32, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 33, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 34 (wherein, optionally, the antibody light chain or The antibody or antigen-binding fragment thereof comprising the antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this (ii) a first form of MUC16 that is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (this first form is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) a second form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing the second form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing one form of or (VIX) A VL CDR1 comprising the amino acid sequence of SEQ ID NO: 38, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 39, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 40 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form) (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (X) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 46, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 47, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 48, wherein optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16 (this first form is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133 (ii) a second form of MUC16, which is non-glycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139; (iii) inhibits Matrigel invasion in vitro of cells recombinantly expressing the first form of MUC16; or (XI) VL CDR1 comprising the amino acid sequence of SEQ ID NO: 52, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 53 and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 54 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (XII) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 58, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 60 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form) (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (XIII) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 66, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 67, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 68 (wherein, optionally, the antibody light chain or The antibody or antigen-binding fragment thereof comprising the antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this (ii) a first form of MUC16 that is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (this first form is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) a second form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing the second form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing one form of or (XIV) A VL CDR1 comprising the amino acid sequence of SEQ ID NO: 72, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 73, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 74 (optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form) (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (XV) VL CDR1 comprising the amino acid sequence of SEQ ID NO: 78, VL CDR2 comprising the amino acid sequence of SEQ ID NO: 79 and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 80 (wherein, optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (XVI) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 86, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 87, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 88 (optionally, an antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this first form) (ii) one form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (wherein the second form is glycosylated, and the amino acid sequence of the first form is SEQ ID NO: 133). (iii) said first form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing said second form of MUC16, wherein the amino acid sequence of said second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing a form of or (XVII) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 92, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 93, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 94 (wherein, optionally, the antibody light chain or The antibody or antigen-binding fragment thereof comprising the antigen-binding portion thereof is capable of binding to (i) a first form of MUC16 (this (ii) a first form of MUC16 that is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (this first form is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) a second form of MUC16 is non-glycosylated and lacks immunospecific binding to cells recombinantly expressing the second form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro of cells recombinantly expressing one form of or (XVIII) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 98, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 99, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 100 (wherein, optionally, the antibody light chain or The antibody or antigen-binding fragment thereof comprising the antigen-binding portion thereof is (i) a first form of MUC16 ( (ii) a first form of MUC16 that is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133; and (iii) a second form of MUC16 that immunospecifically binds to cells recombinantly expressing MUC16 (this the second form is not glycosylated and lacks immunospecific binding to cells recombinantly expressing MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and (iii) inhibits in vitro matrigel invasion of cells recombinantly expressing the first form The antibody light chain or antigen-binding portion thereof, comprising a VL comprising: (Item 93) 1. An antibody light chain, comprising: (I) [ka] (where X 36 is I or V, and X 37 is P or S, and X 38 is R or L, and X 39 is K or H, and X 40 is R or K, and X 41 is E or G, and X 42 is S or G and X 43 is Y or H) Optionally, the antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is capable of binding to (i) a first form of MUC16, which first form is glycosylated, wherein the first form (ii) a second form of MUC16 (the amino acid sequence of which is SEQ ID NO: 133); (iii) a second form of MUC16 (which second form is non-glycosylated, wherein said second form (iii) lacking immunospecific binding to cells recombinantly expressing said first form of MUC16 (the amino acid sequence of which is SEQ ID NO: 139); and (iv) lacking immunospecific binding to cells recombinantly expressing said first form of MUC16 in Matrigel in vitro. inhibits invasion); or (II) the amino acid sequence of SEQ ID NO: 2, wherein, optionally, the antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated; (ii) immunospecifically binds to cells recombinantly expressing a first form of MUC16 (which is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133); (ii) lacks immunospecific binding to cells recombinantly expressing a second form of MUC16 (which second form is unglycosylated, and wherein the amino acid sequence of the second form is SEQ ID NO: 139); and (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16. inhibits matrigel invasion of expressing cells in vitro); or (III) the amino acid sequence of SEQ ID NO: 22, wherein, optionally, the antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is (i) a first form of MUC16 (this first form is Glycine). (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion of expressing cells in vitro); or (IV) the amino acid sequence of SEQ ID NO: 42, optionally comprising the antibody light chain or antigen-binding portion thereof The antibody or antigen-binding fragment thereof comprises: (i) a first form of MUC16 (this first form is Glycine); (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion of expressing cells in vitro); or (V) the amino acid sequence of SEQ ID NO: 62, wherein, optionally, the antibody or antigen-binding fragment thereof comprising the antibody light chain or antigen-binding portion thereof is selected from the group consisting of: (i) a first form of MUC16, which first form is glycosylated (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits matrigel invasion of expressing cells in vitro); or (VI) the amino acid sequence of SEQ ID NO: 82, optionally comprising the antibody light chain or antigen-binding portion thereof The antibody or antigen-binding fragment thereof comprises: (i) a first form of MUC16 (this first form is Glycine); (ii) a second form of MUC16 (which is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); (iii) lacks immunospecific binding to cells recombinantly expressing the first form of MUC16, wherein the amino acid sequence of the second form is SEQ ID NO: 139; and inhibits Matrigel invasion in vitro by cells expressing The antibody light chain comprising a VL comprising: (Item 94) 94. The antibody light chain or antigen-binding portion thereof according to item 92 or 93, wherein the antibody light chain or antigen-binding portion thereof comprises a human-derived light chain constant region. (Item 95) 95. The antibody light chain or antigen-binding portion thereof of item 94, wherein the constant region of the light chain or antigen-binding portion thereof has an isotype selected from the group consisting of kappa and lambda. (Item 96) 93. The antibody light chain or antigen-binding portion thereof of item 92, wherein the antibody light chain or antigen-binding portion thereof is humanized. (Item 97) 97. The antibody light chain or antigen-binding portion thereof of item 96, wherein the antibody light chain or antigen-binding portion thereof is a humanized form of a rodent antibody. (Item 98) 98. An antibody light chain conjugate comprising the antibody light chain or antigen-binding portion thereof according to any one of items 92 to 97, conjugated to a drug. (Item 99) 99. The antibody light chain conjugate of item 98, wherein the agent is an imaging agent or a cytotoxic agent. (Item 100) 99. A fusion protein comprising the antibody light chain of any one of items 92 to 99 conjugated to an scFv via a peptide linker. (Item 101) 101. The fusion protein of paragraph 100, wherein the scFv binds to CD3. (Item 102) 84. A T cell recombinantly expressing the CAR of paragraph 83. (Item 103) A polynucleotide comprising a nucleic acid sequence encoding the scFv according to item 80. (Item 104) 83. A polynucleotide comprising a nucleic acid sequence encoding the scFv conjugate of item 81 or 82. (Item 105) A polynucleotide comprising a nucleic acid sequence encoding the CAR of item 83. (Item 106) 90. A polynucleotide comprising a nucleic acid sequence encoding the antibody heavy chain according to any one of items 84 to 89. (Item 107) 92. A polynucleotide comprising a nucleic acid sequence encoding the antibody heavy chain conjugate of item 90 or 91. (Item 108) 98. A polynucleotide comprising a nucleic acid sequence encoding the antibody light chain according to any one of items 92 to 97. (Item 109) 99. A polynucleotide comprising a nucleic acid sequence encoding the antibody light chain conjugate according to item 98 or 99. Punch. (Item 110) A polynucleotide comprising a nucleic acid sequence encoding the fusion protein according to Item 100 or 101. (Item 111) (a) an antibody heavy chain according to any one of items 84 to 89 or an antibody heavy chain according to item 90 or 91; and (b) a polynucleotide comprising a nucleic acid sequence encoding the antibody light chain according to any one of items 92 to 97, the antibody light chain conjugate according to item 98 or 99, or the fusion protein according to item 100 or 101. (Item 112) 111. A vector comprising the polynucleotide of any one of items 103 to 110 operably linked to a promoter. (Item 113) (a) the polynucleotide of item 106 or 107 operably linked to a first promoter and (b) a vector comprising the polynucleotide of any one of items 108 to 110 operably linked to a second promoter. (Item 114) 106. An ex vivo cell comprising the polynucleotide of any one of items 103 to 105 operably linked to a promoter. (Item 115) 108. An ex vivo cell comprising the polynucleotide of item 106 or 107 operably linked to a promoter. (Item 116) 111. An ex vivo cell comprising the polynucleotide of any one of items 108 to 110 operably linked to a promoter. (Item 117) An ex vivo cell comprising the vector of item 112. (Item 118) An ex vivo cell comprising the vector of item 113. (Item 119) 73. The antibody according to any one of items 1 to 72, or an antibody thereof, operably linked to a promoter. Ex vivo cells comprising one or more polynucleotides encoding the original binding fragments. (Item 120) 116. A method for producing an antibody heavy chain, comprising: culturing the cell of item 115, wherein the polynucleotide is and culturing the polynucleotide under conditions such that the polynucleotide is expressed by the cell to produce the antibody heavy chain or antibody heavy chain conjugate encoded by the polynucleotide. (Item 121) 117. A method for producing an antibody light chain, comprising: culturing the cell of item 116, wherein the polynucleotide is culturing the polynucleotide under conditions such that it is expressed by the cell to produce the antibody light chain, antibody light chain conjugate, or fusion protein encoded by the polynucleotide. (Item 122) A method for producing an antibody or an antigen-binding fragment thereof, comprising the step of: a polynucleotide operably linked to the first promoter and a polynucleotide operably linked to the second promoter are expressed by the cell, and (i) the the antibody heavy chain or the antibody heavy chain conjugate encoded by a polynucleotide; and (ii) culturing under conditions to produce the antibody light chain, the antibody light chain conjugate, or the fusion protein encoded by the polynucleotide. (Item 123) The antibody or antigen-binding fragment thereof according to any one of Items 1 to 72, the antibody or antigen-binding fragment thereof according to Item 73 or 74 the antibody conjugate according to any one of items 75 to 77, the bispecific antibody conjugate according to item 78 or 79, the scFv according to item 80, the scFv conjugate according to item 81 or 82, the CAR according to item 83, the antibody heavy chain according to any one of items 84 to 89, 10. A pharmaceutical composition comprising a therapeutically effective amount of the antibody heavy chain conjugate of item 90 or 91, the antibody light chain of any one of items 92 to 97, the antibody light chain conjugate of item 98 or 99, the fusion protein of item 100 or 101, or the T cell of item 102; and a pharmaceutically acceptable carrier. (Item 124) 124. A method for treating cancer in a patient in need thereof, comprising administering to said patient a medicament according to item 123. The method comprising administering a composition. (Item 125) 125. The method of claim 124, wherein the cancer is lung, pancreatic, breast, uterine, fallopian tube, or primary peritoneal cancer. method. (Item 126) 126. The method of item 124 or 125, wherein the cancer is ovarian cancer. (Item 127) 127. The method of any one of paragraphs 124 to 126, wherein the patient is a human patient. (Item 128) 128. The method of any one of items 124 to 127, wherein the method further comprises administering to the patient a therapeutically effective amount of an additional therapeutic agent. (Item 129) The pharmaceutical composition is the antibody or antigen-binding fragment thereof according to any one of items 1 to 72. a therapeutically effective amount of a first antibody, wherein the antibody or antigen-binding fragment thereof is selected from the group consisting of SEQ ID NO: 150 wherein the additional therapeutic agent recognizes an epitope in MUC16 that includes N-glycosylated Asn1806 of SEQ ID NO: 150 but does not include N-glycosylated Asn1800 of SEQ ID NO: 150; and a fragment thereof, wherein the second antibody or antigen-binding fragment thereof is an N-glycosyltransferase of SEQ ID NO: 150. 129. The method of claim 128, wherein the antibody recognizes an epitope in MUC16 that contains N-glycosylated Asn1806 and also contains N-glycosylated Asn1800 of SEQ ID NO: 150. (Item 130) the first antibody or antigen-binding fragment thereof is (i) a first form of MUC16, wherein the first form of MUC16 is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) its lack of immunospecific binding to cells recombinantly expressing a third form of MUC16, which third form is glycosylated, and wherein the amino acid sequence of the third form is SEQ ID NO: 139; and (iii) its ability to immunospecifically bind to cells recombinantly expressing a third form of MUC16, which third form is glycosylated, and wherein the amino acid sequence of the third form is SEQ ID NO: 139. a fourth form (which fourth form is glycosylated, wherein the amino acid residue of said fourth form is wherein the nucleic acid sequence is SEQ ID NO: 152; wherein the nucleic acid sequence is SEQ ID NO: 153; the nucleic acid sequence is SEQ ID NO: 154; the nucleic acid sequence is SEQ ID NO: 155; the nucleic acid sequence is SEQ ID NO: 156; the nucleic acid sequence is SEQ ID NO: 157; the nucleic acid sequence is SEQ ID NO: 158; the nucleic acid sequence is SEQ ID NO: 159; the nucleic acid sequence is SEQ ID NO: 160; the nucleic acid sequence is SEQ ID NO: 161; the nucleic acid sequence is SEQ ID NO: 162; the nucleic acid sequence is SEQ ID NO: 163; the nucleic acid sequence is SEQ ID NO: 164; the nucleic acid sequence is SEQ ID NO: 165; the nucleic acid sequence is SEQ ID NO: 166; the nucleic acid sequence is SEQ ID NO: 167; the nucleic acid sequence is SEQ ID NO: 16 the cells recombinantly expressing the fourth form of MUC16 and the cells recombinantly expressing the fourth form of MUC16 are of the same cell type. and The second antibody or antigen-binding fragment thereof binds to (i) a first form of MUC16 (this first form is a group (ii) its ability to immunospecifically bind to cells recombinantly expressing a fifth form of MUC16 (this fifth form is glycosylated, wherein the amino acid sequence of the first form is SEQ ID NO: 133); and The method of paragraph 129, wherein the fifth form is glycosylated, and the fifth form is identified by its lack of immunospecific binding to cells recombinantly expressing MUC16 (wherein the amino acid sequence of the fifth form is SEQ ID NO: 172), wherein the cells recombinantly expressing the first form of MUC16 are of the same type as the cells recombinantly expressing the fifth form of MUC16. (Item 131) The pharmaceutical composition is the antibody or antigen-binding fragment thereof according to any one of items 1 to 72. 129. The method of paragraph 128, comprising a therapeutically effective amount of a first antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof recognizes an epitope in MUC16 comprising N-glycosylated Asn1806 of SEQ ID NO: 150, but not N-glycosylated Asn1800 of SEQ ID NO: 150; and wherein the additional therapeutic agent is a therapeutically effective amount of a second antibody or antigen-binding fragment thereof, wherein the second antibody or antigen-binding fragment thereof recognizes an epitope in MUC16 comprising N-glycosylated Asn1800 of SEQ ID NO: 150, but not N-glycosylated Asn1806 of SEQ ID NO: 150. (Item 132) the first antibody or antigen-binding fragment thereof is (i) a first form of MUC16, wherein the first form of MUC16 is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) its lack of immunospecific binding to cells recombinantly expressing a third form of MUC16, which third form is glycosylated, and wherein the amino acid sequence of the third form is SEQ ID NO: 139; and (iii) its ability to immunospecifically bind to cells recombinantly expressing a third form of MUC16, which third form is glycosylated, and wherein the amino acid sequence of the third form is SEQ ID NO: 139. a fourth form (which fourth form is glycosylated, wherein the amino acid residue of said fourth form is The nucleic acid sequence of the first form of MUC16 is SEQ ID NO: 152), wherein the cells recombinantly expressing the first form of MUC16, the cells recombinantly expressing the third form of MUC16, and the cells recombinantly expressing the fourth form of MUC16 are of the same cell type. and The second antibody or antigen-binding fragment thereof binds to (i) a first form of MUC16 (this first form is a group (ii) its ability to immunospecifically bind to cells recombinantly expressing a first form of MUC16, which is glycosylated, and wherein the amino acid sequence of the first form is SEQ ID NO: 133; (ii) its ability to immunospecifically bind to cells recombinantly expressing a third form of MUC16, which third form of MUC16 is glycosylated, and wherein the amino acid sequence of the third form is SEQ ID NO: 139; and (iii) its ability to immunospecifically bind to cells recombinantly expressing a second form of MUC16, which is glycosylated, and wherein the amino acid sequence of the third form is SEQ ID NO: 139. and wherein the fourth form of MUC16 is glycosylated, and the amino acid sequence of the fourth form is SEQ ID NO: 152; wherein the fourth form of MUC16 is glycosylated, and the amino acid sequence of the fourth form is SEQ ID NO: 152; and wherein the fourth form of MUC16 is glycosylated, and the amino acid sequence of the fourth form is SEQ ID NO: 152; and wherein the fourth form of MUC16 is glycosylated, and the amino acid sequence of the fourth form is SEQ ID NO: 152; the cells recombinantly expressing the fourth form of MUC16 and the cells recombinantly expressing the fourth form of MUC16 are of the same cell type. Item 132. The method of item 131, wherein (Item 133) An immunogenic glycopeptide comprising one or more glycosylation sites, wherein (i) the immunogenic glycopeptide is 10 to 60 amino acid residues, 10 to 30 amino acid residues, 15 to 25 amino acid residues, 15 to 20 amino acid residues, or 15 to 18 amino acid residues in length, and (ii) the glycopeptide comprising one or more glycosylation sites is The immunogenic glycopeptide, wherein at least one of the glycopeptides is bound to a carbohydrate. (Item 134) 134. The immunogenic glycopeptide according to item 133, comprising one, two or three glycosylation sites. (Item 135) 134. The immunogenic glycopeptide according to item 133, comprising a glycosylation site to which a carbohydrate is attached. . (Item 136) 134. The immunogenic glycopeptide according to item 133, comprising two glycosylation sites, each of which is bound to a carbohydrate. (Item 137) 137. The immunogenic glycopeptide according to any one of items 133 to 136, wherein the carbohydrate is an N- or O-linked carbohydrate. (Item 138) 138. The immunogenic glycopeptide according to any one of items 133 to 137, wherein the carbohydrate is a monosaccharide, disaccharide, trisaccharide, tetrasaccharide, or pentasaccharide. (Item 139) The immunogenic glycopeptide according to any one of Items 133 to 137, wherein the carbohydrate is a disaccharide. (Item 140) 139. The immunogenic glycopeptide according to item 139, wherein the disaccharide is chitobiose. (Item 141) Any one of items 133 to 140, wherein the N-terminus of the immunogenic glycopeptide is acetylated. An immunogenic glycopeptide according to paragraph . (Item 142) Items 133 to 141, wherein the C-terminus of the glycopeptide is in the form of an N-methylcarboxamide derivative. The immunogenic glycopeptide described in any one of the above. (Item 143) 143. The immunogenic glycopeptide according to any one of items 133 to 142, conjugated to an immunogenic carrier protein. (Item 144) 144. The immunogenic glycopeptide according to item 143, wherein the immunogenic carrier protein is keyhole limpet hemocyanin. (Item 145) 145. The immunogenic glycopeptide according to any one of items 133 to 144, which is 15 to 18 amino acid residues in length. (Item 146) 146. The immunogenic glycopeptide according to item 145, comprising a glycosylation site linked to chitobiose. Chid. (Item 147) 146. The immunogenic glycopeptide according to item 145, comprising two glycosylation sites, each linked to a chitobiose. (Item 148) 145. The immunogenic glycopeptide according to any one of items 133 to 144, which is 18 amino acid residues in length. (Item 149) 149. The immunogenic glycopeptide according to item 148, comprising two glycosylation sites, each linked to a chitobiose. (Item 150) 145. The immunogenic glycopeptide according to any one of items 133 to 144, which is 15 amino acid residues in length. (Item 151) 151. The immunogenic glycopeptide according to item 150, comprising a glycosylation site linked to chitobiose. Chid. (Item 152) 133 to 151, which comprises at least a 10 amino acid portion of the amino acid sequence of SEQ ID NO: 150, wherein at least one of the one or more glycosylation sites is in said portion of the amino acid sequence. The immunogenic glycopeptide described in any one of the above. (Item 153) 153. The immunogenic glycopeptide according to item 152, comprising the amino acid sequence of SEQ ID NO: 129. (Item 154) 154. The immunogenic glycopeptide according to item 153, comprising a glycosylation site at the 30th residue (Asn) of SEQ ID NO: 129 linked to chitobiose. (Item 155) Glycosyl at residue 30 (Asn) of SEQ ID NO: 129 attached to the Man3GlcNAc2 moiety 154. The immunogenic glycopeptide according to item 153, comprising a glycosylation site. (Item 156) 153. The immunogenic glycopeptide according to item 152, comprising the amino acid sequence of SEQ ID NO: 130. (Item 157) 157. The immunogenic glycopeptide according to item 156, comprising two glycosylation sites at the 4th residue (Asn) and the 10th residue (Asn) of SEQ ID NO: 130, each of which is linked to chitobiose. (Item 158) 153. The immunogenic glycopeptide according to item 152, comprising the amino acid sequence of SEQ ID NO: 131. (Item 159) Glycosylation site at the 7th residue (Asn) of SEQ ID NO: 131 bound to chitobiose 159. The immunogenic glycopeptide according to item 158, comprising the amino acid sequence (Item 160) A method for producing an antibody or antigen-binding fragment thereof that specifically binds to a glycoprotein, comprising immunizing a subject with an immunogenic glycopeptide that comprises one or more glycosylation sites, (i) the immunogenic glycopeptide is a glycopeptide having 10 to 60 amino acid residues, 10 to 30 amino acid residues, 15 to 25 amino acid residues, (ii) the length of the immunoglobulin is 15 to 20 amino acid residues, or 15 to 18 amino acid residues; (iii) at least one of the one or more glycosylation sites is linked to a carbohydrate; and (iv) at least one of the one or more glycosylation sites is in the portion of the amino acid sequence. How to write. (Item 161) 161. The method of item 160, wherein the antibody or antigen-binding fragment thereof lacks specific binding to the non-glycosylated form of the glycoprotein. (Item 162) 162. The method of any one of paragraphs 160 or 161, wherein the subject is a goat, sheep, donkey, chicken, guinea pig, rat, rabbit, or mouse. (Item 163) 162. The method of any one of paragraphs 160 or 161, wherein the subject is a rat, rabbit, or mouse. (Item 164) 162. The method of any of paragraphs 160 or 161, wherein the subject is a mouse. (Item 165) 165. The method of any one of items 160 to 164, wherein the immunogenic glycopeptide comprises one, two, or three glycosylation sites. (Item 166) 165. The method of any one of items 160 to 164, wherein the immunogenic glycopeptide comprises a glycosylation site to which a carbohydrate is attached. (Item 167) The immunogenic glycopeptide contains two glycosylation sites, each of which is attached to a carbohydrate. The method according to any one of items 160 to 164. (Item 168) 168. The method of any one of items 160 to 167, wherein the carbohydrate is an N- or O-linked carbohydrate. (Item 169) 169. The method of any one of items 160 to 168, wherein the carbohydrate is a monosaccharide, disaccharide, trisaccharide, tetrasaccharide, or pentasaccharide. (Item 170) 169. The method of any one of items 160 to 168, wherein the carbohydrate is a disaccharide. (Item 171) 171. The method according to item 170, wherein the disaccharide is chitobiose. (Item 172) 172. Any one of items 160 to 171, wherein the N-terminus of the immunogenic glycopeptide is acetylated. The method described in section. (Item 173) Items 160 to 172, wherein the C-terminus of the glycopeptide is in the form of an N-methylcarboxamide derivative. The method according to any one of the preceding claims. (Item 174) 174. The method of any one of items 160 to 173, wherein the antibody is conjugated to an immunogenic carrier protein. (Item 175) 175. The method of item 174, wherein the immunogenic carrier protein is keyhole limpet hemocyanin. (Item 176) 176. The method according to any one of items 160 to 175, wherein the immunogenic glycopeptide is 15 to 18 amino acid residues in length. (Item 177) 177. The method of item 176, wherein the immunogenic glycopeptide comprises a glycosylation site linked to chitobiose. (Item 178) The immunogenic glycopeptide has two glycosylation sites, each of which is linked to chitobiose. 177. The method of item 176, comprising: (Item 179) 176. The method of any one of items 160 to 175, wherein the immunogenic glycopeptide is 18 amino acid residues in length. (Item 180) The immunogenic glycopeptide has two glycosylation sites, each of which is linked to chitobiose. Item 179. The method of item 179, comprising: (Item 181) 176. The method of any one of items 160 to 175, wherein the immunogenic glycopeptide is 15 amino acid residues in length. (Item 182) 182. The method of item 181, wherein the immunogenic glycopeptide comprises a glycosylation site linked to chitobiose. (Item 183) 183. Any one of items 160 to 182, wherein the glycoprotein comprises the amino acid sequence of SEQ ID NO: 150. The method described. (Item 184) 184. The method of item 183, wherein the immunogenic glycopeptide comprises the amino acid sequence of SEQ ID NO: 129. (Item 185) 185. The method of item 184, wherein the immunogenic glycopeptide comprises a glycosylation site at residue 30 (Asn) of SEQ ID NO: 129 linked to chitobiose. (Item 186) 185. The method of item 184, wherein the immunogenic glycopeptide comprises a glycosylation site at residue 30 (Asn) of SEQ ID NO: 129 linked to a Man3GlcNAc2 moiety. (Item 187) 184. The method of item 183, wherein the immunogenic glycopeptide comprises the amino acid sequence of SEQ ID NO: 130. (Item 188) 188. The method of item 187, wherein the immunogenic glycopeptide comprises two glycosylation sites at the 4th residue (Asn) and the 10th residue (Asn) of SEQ ID NO: 130, each of which is linked to chitobiose. (Item 189) 184. The method of item 183, wherein the immunogenic glycopeptide comprises the amino acid sequence of SEQ ID NO: 131. (Item 190) 189. The method of item 189, wherein the immunogenic glycopeptide comprises a glycosylation site at the seventh residue (Asn) of SEQ ID NO: 131 linked to chitobiose. [Brief explanation of the drawings]

[0164] (4. Brief description of the drawings) [Figure 1A-B]Figures 1A-1I. MUC16 Constructs. Figure 1A: Schematic representation of MUC16. Figure 1B: Top: Schematic representation of MUC16. Bottom: Linear representation of the truncated MUC16 construct. The amino acid sequence of the N-terminus of the first tandem repeat is as set forth in SEQ ID NO: 155. The amino acid sequence of the C-terminus of the first tandem repeat is as set forth in SEQ ID NO: 156. The amino acid sequence of the N-terminus of the ectodomain is as set forth in SEQ ID NO: 157. The amino acid sequence of the C-terminus of the ectodomain is as set forth in SEQ ID NO: 158. Figure 1C: Top: Schematic representation of MUC16. Bottom: Linear representation of MUC16. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 161. The amino acid sequence of the transmembrane segment is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic tail is as set forth in SEQ ID NO: 159. Figure ID: Top: Schematic representation of MUC16c80. Bottom: Linear representation of MUC16c80. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 162. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic tail is as set forth in SEQ ID NO: 159. Figure IE: Top: Schematic representation of MUC16c86. Bottom: Linear representation of MUC16c86. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 163. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 164. The amino acid sequence of the cytoplasmic domain is SEQ ID NO: 165. Figure IF: Linear representation of MUC16c114-N123. The amino acid sequence of the 58 aa ectodomain with three (N→A) mutations is as set forth in SEQ ID NO: 166. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic domain is as set forth in SEQ ID NO: 160. Figures 1G, 1H, and 1I show the percentage of cells detected by 4H11 by FACS analysis, where the cell lines express the indicated MUC16 constructs. [Figure 1C-D]Figures 1A-1I. MUC16 Constructs. Figure 1A: Schematic representation of MUC16. Figure 1B: Top: Schematic representation of MUC16. Bottom: Linear representation of the truncated MUC16 construct. The amino acid sequence of the N-terminus of the first tandem repeat is as set forth in SEQ ID NO: 155. The amino acid sequence of the C-terminus of the first tandem repeat is as set forth in SEQ ID NO: 156. The amino acid sequence of the N-terminus of the ectodomain is as set forth in SEQ ID NO: 157. The amino acid sequence of the C-terminus of the ectodomain is as set forth in SEQ ID NO: 158. Figure 1C: Top: Schematic representation of MUC16. Bottom: Linear representation of MUC16. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 161. The amino acid sequence of the transmembrane segment is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic tail is as set forth in SEQ ID NO: 159. Figure 1D: Top: Schematic representation of MUC16c80. Bottom: Linear representation of MUC16c80. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 162. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic tail is as set forth in SEQ ID NO: 159. Figure 1E: Top: Schematic representation of MUC16c86. Bottom: Linear representation of MUC16c86. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 163. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 164. The amino acid sequence of the cytoplasmic domain is SEQ ID NO: 165. Figure 1F: Linear representation of MUC16c114-N123. The amino acid sequence of the 58 aa ectodomain with three (N→A) mutations is as set forth in SEQ ID NO: 166. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic domain is as set forth in SEQ ID NO: 160. Figures 1G, 1H, and 1I show the percentage of cells detected by 4H11 by FACS analysis, where the cell lines express the indicated MUC16 constructs. [Figure 1E-F]Figures 1A-1I. MUC16 Constructs. Figure 1A: Schematic representation of MUC16. Figure 1B: Top: Schematic representation of MUC16. Bottom: Linear representation of the truncated MUC16 construct. The amino acid sequence of the N-terminus of the first tandem repeat is as set forth in SEQ ID NO: 155. The amino acid sequence of the C-terminus of the first tandem repeat is as set forth in SEQ ID NO: 156. The amino acid sequence of the N-terminus of the ectodomain is as set forth in SEQ ID NO: 157. The amino acid sequence of the C-terminus of the ectodomain is as set forth in SEQ ID NO: 158. Figure 1C: Top: Schematic representation of MUC16. Bottom: Linear representation of MUC16. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 161. The amino acid sequence of the transmembrane segment is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic tail is as set forth in SEQ ID NO: 159. Figure 1D: Top: Schematic representation of MUC16c80. Bottom: Linear representation of MUC16c80. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 162. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic tail is as set forth in SEQ ID NO: 159. Figure 1E: Top: Schematic representation of MUC16c86. Bottom: Linear representation of MUC16c86. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 163. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 164. The amino acid sequence of the cytoplasmic domain is SEQ ID NO: 165. Figure 1F: Linear representation of MUC16c114-N123. The amino acid sequence of the 58 aa ectodomain with three (N→A) mutations is as set forth in SEQ ID NO: 166. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic domain is as set forth in SEQ ID NO: 160. Figures 1G, 1H, and 1I show the percentage of cells detected by 4H11 by FACS analysis, where the cell lines express the indicated MUC16 constructs. [Figure 1G-I]Figures 1A-1I. MUC16 Constructs. Figure 1A: Schematic representation of MUC16. Figure 1B: Top: Schematic representation of MUC16. Bottom: Linear representation of the truncated MUC16 construct. The amino acid sequence of the N-terminus of the first tandem repeat is as set forth in SEQ ID NO: 155. The amino acid sequence of the C-terminus of the first tandem repeat is as set forth in SEQ ID NO: 156. The amino acid sequence of the N-terminus of the ectodomain is as set forth in SEQ ID NO: 157. The amino acid sequence of the C-terminus of the ectodomain is as set forth in SEQ ID NO: 158. Figure 1C: Top: Schematic representation of MUC16. Bottom: Linear representation of MUC16. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 161. The amino acid sequence of the transmembrane segment is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic tail is as set forth in SEQ ID NO: 159. Figure ID: Top: Schematic representation of MUC16c80. Bottom: Linear representation of MUC16c80. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 162. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic tail is as set forth in SEQ ID NO: 159. Figure IE: Top: Schematic representation of MUC16c86. Bottom: Linear representation of MUC16c86. The amino acid sequence of the ectodomain is as set forth in SEQ ID NO: 163. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 164. The amino acid sequence of the cytoplasmic domain is SEQ ID NO: 165. Figure IF: Linear representation of MUC16c114-N123. The amino acid sequence of the 58 aa ectodomain with three (N→A) mutations is as set forth in SEQ ID NO: 166. The amino acid sequence of the transmembrane domain is as set forth in SEQ ID NO: 159. The amino acid sequence of the cytoplasmic domain is as set forth in SEQ ID NO: 160. Figures 1G, 1H, and 1I show the percentage of cells detected by 4H11 by FACS analysis, where the cell lines express the indicated MUC16 constructs.

[0165] [Figure 2]Figures 2A-2C. In vitro growth curves of MUC16 transfectants. Figure 2A shows the in vitro growth curves of the MUC16 and MUC16 cell lines compared to a control cell line (phrGFP) in 3T3 cells. Figure 2B shows the in vitro growth curves of the MUC16 and MUC16 cell lines compared to a control cell line (phrGFP) in A2780 cells. Figure 2C shows the in vitro growth curves of the MUC16, MUC16, and MUC16 cell lines compared to a control cell line (phrGFP) in 3T3 cells.

[0166] [Figure 3A-C]Figures 3A-3E. Effect of MUC16 on 3T3 cells. Figure 3A shows soft agar growth of 3T3 transfectants in 60 mm dishes. After 14 days, colonies were counted and plotted. Data shown in the table represent one of three similar experiments compared to soft agar growth of cells expressing a phrGFP control vector (***p<0.0001). Figure 3B shows Matrigel invasion assays of 3T3 cell lines after stable transfection with a phrGFP control vector or MUC16 or MUC16 carboxy-terminal constructs. Each assay was performed at least twice in triplicate and counted manually. Both the MUC16 and MUC16 cell lines were significantly more invasive than cells expressing the phrGFP vector control (***p<0.0001), and the results for the MUC16 cell line were significantly different from those for the MUC16 cell line (#p=0.0354). Figure 3C shows the expression of metastasis and invasion genes induced by MUC16 and MUC16 expression. A SuperArray panel of 80 invasion / metastasis gene transcripts was examined in MUC16 construct-positive and vector-only cell lines. Expression of selected chemotaxis, adhesion, and invasion transcripts was measured in 3T3-MUC16 or 3T3-MUC16 cell lines (each of three triplicates was examined in duplicate and compared to the phr vector-only control by chi-square test). The p-value for each transcript, adjusted for repeated measurements, is shown in the table. All genes with a change in p<0.05 or less are included. (Figure 3D) Transfected 3T3 cells were examined for activation of the ERK / AKT signaling pathway compared to vector-only controls. Phosphorylation of ERK1 / 2 (pT202 / Y204) and AKT (S473) was increased after expression of the MUC16 and MUC16 constructs compared to expression of the phr vector. Activation of both pathways was observed in each of the cell lines. B-actin-normalized densitometry quantification is shown below each Western blot in the figure. (Figure 3E) shows MUC16 construct-positive tumor growth in athymic nude mice.Two million tumor cells were introduced into the flanks of 15 nu / nu mice, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. The difference in mean tumor volume was significantly greater in mice bearing MUC16 construct-positive tumors (p<0.0001 for both strains compared to cells expressing the phrGFP control vector). [Figure 3D-E]Figures 3A-3E. Effect of MUC16 on 3T3 cells. Figure 3A shows soft agar growth of 3T3 transfectants in 60 mm dishes. After 14 days, colonies were counted and plotted. Data shown in the table represent one of three similar experiments compared to soft agar growth of cells expressing a phrGFP control vector (***p<0.0001). Figure 3B shows Matrigel invasion assays of 3T3 cell lines after stable transfection with a phrGFP control vector or MUC16 or MUC16 carboxy-terminal constructs. Each assay was performed at least twice in triplicate and counted manually. Both the MUC16 and MUC16 cell lines were significantly more invasive than cells expressing the phrGFP vector control (***p<0.0001), and the results for the MUC16 cell line were significantly different from those for the MUC16 cell line (#p=0.0354). Figure 3C shows the expression of metastasis and invasion genes induced by MUC16 and MUC16 expression. A SuperArray panel of 80 invasion / metastasis gene transcripts was examined in MUC16 construct-positive and vector-only cell lines. Expression of selected chemotaxis, adhesion, and invasion transcripts was measured in 3T3-MUC16 or 3T3-MUC16 cell lines (each of three triplicates was examined in duplicate and compared to the phr vector-only control by chi-square test). The p-value for each transcript, adjusted for repeated measurements, is shown in the table. All genes with a change in p<0.05 or less are included. (Figure 3D) Transfected 3T3 cells were examined for activation of the ERK / AKT signaling pathway compared to vector-only controls. Phosphorylation of ERK1 / 2 (pT202 / Y204) and AKT (S473) was increased after expression of the MUC16 and MUC16 constructs compared to expression of the phr vector. Activation of both pathways was observed in each of the cell lines. B-actin-normalized densitometry quantification is shown below each Western blot in the figure. (Figure 3E) shows MUC16 construct-positive tumor growth in athymic nude mice.Two million tumor cells were introduced into the flanks of 15 nu / nu mice, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. The difference in mean tumor volume was significantly greater in mice bearing MUC16 construct-positive tumors (p<0.0001 for both strains compared to cells expressing the phrGFP control vector).

[0167] [Figure 4] Figures 4A-4C. Oncogenic properties of MUC16 fragments. Figure 4A shows Matrigel invasion assays of A2780 cell lines transfected with either the phrGFP control vector or the MUC16 carboxy-terminal expression vectors MUC16 or MUC16. Each assay was performed at least twice in triplicate and counted manually. Results were compared to Matrigel invasion of cells expressing the phrGFP control vector or MUC16. The MUC16 or MUC16 cell lines showed significant Matrigel invasion compared to the phrGFP vector control, and the results for the MUC16 cell line were significantly different from those for the MUC16 (p = 0.0018). Figure 4B shows the effect of MUC16 expression on ERK / AKT signaling. A2780 cells were examined for activation of the ERK / AKT signaling pathway. Phosphorylation of ERK1 / 2 (pT202 / Y204) and AKT (S473) was increased after expression of each of the MUC16 expression constructs. Both pathways were activated in each of the cell lines. β-Actin-normalized densitometry quantification values ​​are shown below each Western blot in the figure. Figure 4C shows MUC16 construct-positive tumor growth in athymic nude mice. Two million tumor cells were introduced into the flanks of 15 nu / nu mice, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. The difference in mean tumor volume was significantly greater in mice bearing either MUC16 or MUC16 tumors on day 28, as shown in the figure.

[0168] [Figure 5A-B]Figures 5A-5D: Effect of truncated MUC16 mutants. Figure 5A: Soft agar growth. 3T3 transfectants expressing either the endodomain or ectodomain portions of MUC16 were layered onto soft agar as described in Section 6.1.2. Colonies were counted and plotted. Data shown represent one of three experiments. The soft agar growth rates of MUC16 and MUC16 were significantly different compared to that of MUC16 (p=0.0111 and p=0.0258, respectively), although a greater significance level was seen for the growth rate of MUC1680 transfectants compared to that of MUC16 transfectants (p<0.0001). Figure 5B shows Matrigel invasion assays of 3T3 cell lines transfected with either the phrGFP control vector or the MUC16 carboxy-terminal construct. Each assay was performed at least twice in triplicate and counted manually. Invasion of MUC16 transfectant cells was significantly higher than that of the MUC16 cell line (p=0.0172). Figure 5C shows the effect of MUC16 expression on ERK / AKT signaling. Transfected 3T3 cells were examined for activation of the ERK / AKT signaling pathway. Phosphorylation of ERK1 / 2 (pT202 / Y204) and AKT (S473) increased after MUC16; however, the signal was lower in cells transfected with the MUC16 or MUC16 constructs. β-Actin-normalized densitometry quantification values ​​are shown below each Western blot in the figure. Figure 5D shows MUC16 construct-positive tumor growth in athymic nude mice. Two million tumor cells were introduced into the flanks of 20 nu / nu mice, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. The difference in mean tumor volume was significantly greater in mice bearing MUC16+ tumors. 3T3 MUC16 and 3T3 MUC16 transfectants were significantly different compared to MUC16 transfectants (p<0.0001). [Figure 5C-D]Figures 5A-5D: Effect of truncated MUC16 mutants. Figure 5A: Soft agar growth. 3T3 transfectants expressing either the endodomain or ectodomain portions of MUC16 were layered onto soft agar as described in Section 6.1.2. Colonies were counted and plotted. Data shown represent one of three experiments. The soft agar growth rates of MUC16 and MUC16 were significantly different compared to that of MUC16 (p=0.0111 and p=0.0258, respectively), although a greater significance level was seen for the growth rate of MUC1680 transfectants compared to that of MUC16 transfectants (p<0.0001). Figure 5B shows Matrigel invasion assays of 3T3 cell lines transfected with either the phrGFP control vector or the MUC16 carboxy-terminal construct. Each assay was performed at least twice in triplicate and counted manually. Invasion of MUC16 transfectant cells was significantly higher than that of the MUC16 cell line (p=0.0172). Figure 5C shows the effect of MUC16 expression on ERK / AKT signaling. Transfected 3T3 cells were examined for activation of the ERK / AKT signaling pathway. Phosphorylation of ERK1 / 2 (pT202 / Y204) and AKT (S473) increased after MUC16; however, the signal was lower in cells transfected with the MUC16 or MUC16 constructs. β-Actin-normalized densitometry quantification values ​​are shown below each Western blot in the figure. Figure 5D shows MUC16 construct-positive tumor growth in athymic nude mice. Two million tumor cells were introduced into the flanks of 20 nu / nu mice, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. The difference in mean tumor volume was significantly greater in mice bearing MUC16+ tumors. 3T3 MUC16 and 3T3 MUC16 transfectants were significantly different compared to MUC16 transfectants (p<0.0001).

[0169] [Figure 6] Figures 6A-6B. Amino acid sequences of MUC16 (amino acid residues 1777-1890 (SEQ ID NO: 133), Figure 6A) and MUC16 (amino acid residues 1547-1890 (SEQ ID NO: 132), Figure 6B). N- and O-glycosylation sites are highlighted, and the transmembrane domain (amino acid residues 1835-1859) is underlined and labeled "Transmembrane Domain." Amino acid residues 1857-1884 correspond to the 28 amino acid endodomain deletion present in the MUC16 construct (see Figure 1). Amino acid residues 1798-1831 correspond to the 34 amino acid ectodomain deletion present in the MUC16 construct (see Figure 1).

[0170] [Figure 7A-B]Figures 7A-7H. Effect of N-glycosylation on MUC16 transformation. Figure 7A shows Matrigel invasion assays of 3T3 cell lines transfected with phrGFP control vector, MUC16, or MUC16-N123, and 3T3 cell lines transfected with MUC16 and treated with 0.1 μg / mL tunicamycin. Results for the MUC16 cell line were significantly different from those for the phrGFP vector control cell line (p<0.0001). Results for the MUC16-N123 cell line were significantly different from those for the phrGFP vector control cell line (p=0.007). Treatment with the N-glycosylation inhibitor tunicamycin significantly inhibited Matrigel invasion compared to untreated MUC16 (p=0.004). Figure 7B shows Matrigel invasion assays of 3T3 transfected cell lines compared to the phrGFP control vector. MUC16-transfected 3T3 cells were treated with medium alone or with 5 μg / mL of control pFUSEhIgG1-Fc2 fusion protein, 5 μg / mL of MUC16-pFUSEhIgG1-Fc2 fusion protein, or 5 μg / mL of 117-244LGALS3-pFUSEhIgG1-Fc2 fusion protein, as detailed in Figure 8. The MUC16 cell line was significantly more invasive than control 3T3 cells expressing the phrGFP vector control (***p<0.0001), which was not affected by exposure to the pFUSE vector alone. In contrast, MUC16 cell lines treated with the MUC16-pFUSEhIgG1-Fc2 fusion protein or the 117-244LGALS3-pFUSEhIgG1-Fc2 fusion protein showed significant inhibition of Matrigel invasion compared to MUC16 control cells. Figure 7C shows the effect of MUC16 expression on ERK / AKT signaling. Transfected 3T3 cells were also examined for activation of the ERK / AKT signaling pathway.Phosphorylation of ERK1 / 2 (pT202 / Y204) and AKT (S473) was increased in 3T3 cells transfected with MUC16; the effect was reduced in 3T3 cells transfected with the MUC16-N123 vector ("MUC16-N123" and "MUC163(N-->A)" are used interchangeably herein). Despite the three asparagine-to-alanine mutations, Western blot analysis using an anti-MUC16 antibody (4H11 mAb) showed a higher signal than cells transfected with either the phrGFP vector control or native MUC16, indicating that high levels of MUC163(N-->A) protein were expressed in transfected 3T3 cells. As used herein, "4H11" refers to the monoclonal anti-MUC16 antibody designated as 4H11 in Rao et al., Appl. Immunohistochem. Mol. Morphol. 2010, 18(5):462-72 and International Patent Application Publication No. WO 2011 / 119979. Figure 7D shows MUC16 construct-positive tumor growth in athymic nude mice. Two million tumor cells were introduced into the flanks of 20 nu / nu mice, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. The difference in mean tumor volume was significantly greater in mice bearing MUC16 tumors (p<0.0001). Results with 3T3-MUC16 transfectants were highly significant compared with results with the phrGFP control vector cell line (***p<0.0001). However, MUC16-N123 3T3 transfectants showed no significant difference compared to phrGFP vector control 3T3 cells, indicating that N-glycosylation mutation dramatically reduced tumor growth and invasion. Figure 7E shows a linear representation of the MUC16-pFUSE-human IgG1-Fc2 construct. The amino acid sequence of the ectodomain is set forth in SEQ ID NO: 161.Figure 7F shows protein levels of the MUC16-114-pFUSE-human-IgG1-Fc2 construct as determined by the indicated antibodies. Figure 7G shows a linear representation of the 117-244LGALS3-pFUSE-human-IgG1-Fc2 construct. The amino acid sequence of the carbohydrate-binding domain is as set forth in SEQ ID NO: 167. Figure 7H shows protein levels of the 17-244LGALS3-pFUSE-human-IgG1-Fc2 construct as determined by the indicated antibodies. [Figure 7C-D]Figures 7A-7H. Effect of N-glycosylation on MUC16 transformation. Figure 7A shows Matrigel invasion assays of 3T3 cell lines transfected with phrGFP control vector, MUC16, or MUC16-N123, and 3T3 cell lines transfected with MUC16 and treated with 0.1 μg / mL tunicamycin. Results for the MUC16 cell line were significantly different from those for the phrGFP vector control cell line (p<0.0001). Results for the MUC16-N123 cell line were significantly different from those for the phrGFP vector control cell line (p=0.007). Treatment with the N-glycosylation inhibitor tunicamycin significantly inhibited Matrigel invasion compared to untreated MUC16 (p=0.004). Figure 7B shows Matrigel invasion assays of 3T3 transfected cell lines compared to the phrGFP control vector. MUC16-transfected 3T3 cells were treated with medium alone or with 5 μg / mL of control pFUSEhIgG1-Fc2 fusion protein, 5 μg / mL of MUC16-pFUSEhIgG1-Fc2 fusion protein, or 5 μg / mL of 117-244LGALS3-pFUSEhIgG1-Fc2 fusion protein, as detailed in Figure 8. The MUC16 cell line was significantly more invasive than control 3T3 cells expressing the phrGFP vector control (***p<0.0001), which was not affected by exposure to the pFUSE vector alone. In contrast, MUC16 cell lines treated with the MUC16-pFUSEhIgG1-Fc2 fusion protein or the 117-244LGALS3-pFUSEhIgG1-Fc2 fusion protein showed significant inhibition of Matrigel invasion compared to MUC16 control cells. Figure 7C shows the effect of MUC16 expression on ERK / AKT signaling. Transfected 3T3 cells were also examined for activation of the ERK / AKT signaling pathway.Phosphorylation of ERK1 / 2 (pT202 / Y204) and AKT (S473) was increased in 3T3 cells transfected with MUC16; the effect was reduced in 3T3 cells transfected with the MUC16-N123 vector ("MUC16-N123" and "MUC163(N-->A)" are used interchangeably herein). Despite the three asparagine-to-alanine mutations, Western blot analysis using an anti-MUC16 antibody (4H11 mAb) showed a higher signal than cells transfected with either the phrGFP vector control or native MUC16, indicating that high levels of MUC163(N-->A) protein were expressed in transfected 3T3 cells. As used herein, "4H11" refers to the monoclonal anti-MUC16 antibody designated as 4H11 in Rao et al., Appl. Immunohistochem. Mol. Morphol. 2010, 18(5):462-72 and International Patent Application Publication No. WO 2011 / 119979. Figure 7D shows MUC16 construct-positive tumor growth in athymic nude mice. Two million tumor cells were introduced into the flanks of 20 nu / nu mice, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. The difference in mean tumor volume was significantly greater in mice bearing MUC16 tumors (p<0.0001). Results with 3T3-MUC16 transfectants were highly significant compared with results with the phrGFP control vector cell line (***p<0.0001). However, MUC16-N123 3T3 transfectants showed no significant difference compared to phrGFP vector control 3T3 cells, indicating that N-glycosylation mutation dramatically reduced tumor growth and invasion. Figure 7E shows a linear representation of the MUC16-pFUSE-human IgG1-Fc2 construct. The amino acid sequence of the ectodomain is set forth in SEQ ID NO: 161.Figure 7F shows protein levels of the MUC16-114-pFUSE-human-IgG1-Fc2 construct as determined by the indicated antibodies. Figure 7G shows a linear representation of the 117-244LGALS3-pFUSE-human-IgG1-Fc2 construct. The amino acid sequence of the carbohydrate-binding domain is as set forth in SEQ ID NO: 167. Figure 7H shows protein levels of the 17-244LGALS3-pFUSE-human-IgG1-Fc2 construct as determined by the indicated antibodies. [Figure 7E-F]Figures 7A-7H. Effect of N-glycosylation on MUC16 transformation. Figure 7A shows Matrigel invasion assays of 3T3 cell lines transfected with phrGFP control vector, MUC16, or MUC16-N123, and 3T3 cell lines transfected with MUC16 and treated with 0.1 μg / mL tunicamycin. Results for the MUC16 cell line were significantly different from those for the phrGFP vector control cell line (p<0.0001). Results for the MUC16-N123 cell line were significantly different from those for the phrGFP vector control cell line (p=0.007). Treatment with the N-glycosylation inhibitor tunicamycin significantly inhibited Matrigel invasion compared to untreated MUC16 (p=0.004). Figure 7B shows Matrigel invasion assays of 3T3 transfected cell lines compared to the phrGFP control vector. MUC16-transfected 3T3 cells were treated with medium alone or with 5 μg / mL of control pFUSEhIgG1-Fc2 fusion protein, 5 μg / mL of MUC16-pFUSEhIgG1-Fc2 fusion protein, or 5 μg / mL of 117-244LGALS3-pFUSEhIgG1-Fc2 fusion protein, as detailed in Figure 8. The MUC16 cell line was significantly more invasive than control 3T3 cells expressing the phrGFP vector control (***p<0.0001), which was not affected by exposure to the pFUSE vector alone. In contrast, MUC16 cell lines treated with the MUC16-pFUSEhIgG1-Fc2 fusion protein or the 117-244LGALS3-pFUSEhIgG1-Fc2 fusion protein showed significant inhibition of Matrigel invasion compared to MUC16 control cells. Figure 7C shows the effect of MUC16 expression on ERK / AKT signaling. Transfected 3T3 cells were also examined for activation of the ERK / AKT signaling pathway.Phosphorylation of ERK1 / 2 (pT202 / Y204) and AKT (S473) was increased in 3T3 cells transfected with MUC16; the effect was reduced in 3T3 cells transfected with the MUC16-N123 vector ("MUC16-N123" and "MUC163(N-->A)" are used interchangeably herein). Despite the three asparagine-to-alanine mutations, Western blot analysis using an anti-MUC16 antibody (4H11 mAb) showed a higher signal than cells transfected with either the phrGFP vector control or native MUC16, indicating that high levels of MUC163(N-->A) protein were expressed in transfected 3T3 cells. As used herein, "4H11" refers to the monoclonal anti-MUC16 antibody designated as 4H11 in Rao et al., Appl. Immunohistochem. Mol. Morphol. 2010, 18(5):462-72 and International Patent Application Publication No. WO 2011 / 119979. Figure 7D shows MUC16 construct-positive tumor growth in athymic nude mice. Two million tumor cells were introduced into the flanks of 20 nu / nu mice, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. The difference in mean tumor volume was significantly greater in mice bearing MUC16 tumors (p<0.0001). Results with 3T3-MUC16 transfectants were highly significant compared with results with the phrGFP control vector cell line (***p<0.0001). However, MUC16-N123 3T3 transfectants showed no significant difference compared to phrGFP vector control 3T3 cells, indicating that N-glycosylation mutation dramatically reduced tumor growth and invasion. Figure 7E shows a linear representation of the MUC16-pFUSE-human IgG1-Fc2 construct. The amino acid sequence of the ectodomain is set forth in SEQ ID NO: 161.Figure 7F shows protein levels of the MUC16-114-pFUSE-human-IgG1-Fc2 construct as determined by the indicated antibodies. Figure 7G shows a linear representation of the 117-244LGALS3-pFUSE-human-IgG1-Fc2 construct. The amino acid sequence of the carbohydrate-binding domain is as set forth in SEQ ID NO: 167. Figure 7H shows protein levels of the 17-244LGALS3-pFUSE-human-IgG1-Fc2 construct as determined by the indicated antibodies. [Figure 7G-H]Figures 7A-7H. Effect of N-glycosylation on MUC16 transformation. Figure 7A shows Matrigel invasion assays of 3T3 cell lines transfected with phrGFP control vector, MUC16, or MUC16-N123, and 3T3 cell lines transfected with MUC16 and treated with 0.1 μg / mL tunicamycin. Results for the MUC16 cell line were significantly different from those for the phrGFP vector control cell line (p<0.0001). Results for the MUC16-N123 cell line were significantly different from those for the phrGFP vector control cell line (p=0.007). Treatment with the N-glycosylation inhibitor tunicamycin significantly inhibited Matrigel invasion compared to untreated MUC16 (p=0.004). Figure 7B shows Matrigel invasion assays of 3T3 transfected cell lines compared to the phrGFP control vector. MUC16-transfected 3T3 cells were treated with medium alone or with 5 μg / mL of control pFUSEhIgG1-Fc2 fusion protein, 5 μg / mL of MUC16-pFUSEhIgG1-Fc2 fusion protein, or 5 μg / mL of 117-244LGALS3-pFUSEhIgG1-Fc2 fusion protein, as detailed in Figure 8. The MUC16 cell line was significantly more invasive than control 3T3 cells expressing the phrGFP vector control (***p<0.0001), which was not affected by exposure to the pFUSE vector alone. In contrast, MUC16 cell lines treated with the MUC16-pFUSEhIgG1-Fc2 fusion protein or the 117-244LGALS3-pFUSEhIgG1-Fc2 fusion protein showed significant inhibition of Matrigel invasion compared to MUC16 control cells. Figure 7C shows the effect of MUC16 expression on ERK / AKT signaling. Transfected 3T3 cells were also examined for activation of the ERK / AKT signaling pathway.Phosphorylation of ERK1 / 2 (pT202 / Y204) and AKT (S473) was increased in 3T3 cells transfected with MUC16; the effect was reduced in 3T3 cells transfected with the MUC16-N123 vector ("MUC16-N123" and "MUC163(N-->A)" are used interchangeably herein). Despite the three asparagine-to-alanine mutations, Western blot analysis using an anti-MUC16 antibody (4H11 mAb) showed a higher signal than cells transfected with either the phrGFP vector control or native MUC16, indicating that high levels of MUC163(N-->A) protein were expressed in transfected 3T3 cells. As used herein, "4H11" refers to the monoclonal anti-MUC16 antibody designated as 4H11 in Rao et al., Appl. Immunohistochem. Mol. Morphol. 2010, 18(5):462-72 and International Patent Application Publication No. WO 2011 / 119979. Figure 7D shows MUC16 construct-positive tumor growth in athymic nude mice. Two million tumor cells were introduced into the flanks of 20 nu / nu mice, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. The difference in mean tumor volume was significantly greater in mice bearing MUC16 tumors (p<0.0001). Results with 3T3-MUC16 transfectants were highly significant compared with results with the phrGFP control vector cell line (***p<0.0001). However, MUC16-N123 3T3 transfectants showed no significant difference compared to phrGFP vector control 3T3 cells, indicating that N-glycosylation mutation dramatically reduced tumor growth and invasion. Figure 7E shows a linear representation of the MUC16-pFUSE-human IgG1-Fc2 construct. The amino acid sequence of the ectodomain is set forth in SEQ ID NO: 161.Figure 7F shows protein levels of the MUC16-114-pFUSE-human-IgG1-Fc2 construct as determined by the indicated antibodies. Figure 7G shows a linear representation of the 117-244LGALS3-pFUSE-human-IgG1-Fc2 construct. The amino acid sequence of the carbohydrate-binding domain is as set forth in SEQ ID NO: 167. Figure 7H shows protein levels of the 17-244LGALS3-pFUSE-human-IgG1-Fc2 construct as determined by the indicated antibodies.

[0171] [Figure 8] Figure 8. Ectodomain-MUC16 (SEQ ID NO: 161; amino acid residues 1777-1834 of MUC16) amino acid sequence inserted into the pFUSE-hIgG1-Fc2 vector to construct MUC16-c57-c114pFUSE as a pseudo-receptor, and the 117-244LGALS3 amino acid sequence (SEQ ID NO: 167) inserted into pFUSE-hIgG1-Fc2 to generate the 117-244LGALS3pFUSE vector.

[0172] [Figure 9A]Figures 9A-9E. MUC16 transgenic mice. Figure 9A shows the strategy for constructing the MUC16 conditional construct. The CMV early enhancer plus chicken β-actin promoter (CAG) was used to drive transcription of hrGFP between two loxP sites and downstream MUC16 sequences. Figure 9B: Southern blots show 12 MUC16-positive founder candidates among 99 animals after microinjection. Figure 9C: Western blots with the anti-MUC16 antibody 4H11 identified founders 9 (~50 copies) and 36 (~10 copies) for MUC16 mouse colony development; A5 is a positive cell derived from a SKOV3 cell line stably transfected with MUC16. Figure 9D: Histological analysis of tumors from MUC16:p53+ / - double transgenic mice. Multiple sarcomas and lymphomas were identified in MUC16:p53+ / - double transgenic mice. Sections were stained with hematoxylin and eosin (H&E). Tumors included histiocytic sarcomas of the uterus (I, scale bar: 100 μm), liver (II, scale bar: 50 μm), ovary (III, scale bar: 50 μm), and bone marrow (IV, scale bar: 50 μm), as well as lymphomas of the ovary (V, scale bar: 50 μm), kidney (VI, scale bar: 50 μm), and lung (VII, scale bar: 50 μm), along with carcinoma of the lung (VIII, scale bar: 50 μm). Figure 9E: Cancer-specific Kaplan-Meier survival curves of transgenic mice. MUC16 mice, like wild-type (WT) mice, did not develop spontaneous tumors over the first 18 months. However, when MUC16 mice were crossed with p53 mice, the double transgenic MUC16:p53 mice exhibited significantly worse overall survival compared with either p53 mice (p<0.014) or MUC16 mice due to spontaneous tumor development. [Figure 9B-C]Figures 9A-9E. MUC16 transgenic mice. Figure 9A shows the strategy for constructing the MUC16 conditional construct. The CMV early enhancer plus chicken β-actin promoter (CAG) was used to drive transcription of hrGFP between two loxP sites and downstream MUC16 sequences. Figure 9B: Southern blots show 12 MUC16-positive founder candidates among 99 animals after microinjection. Figure 9C: Western blots with the anti-MUC16 antibody 4H11 identified founders 9 (~50 copies) and 36 (~10 copies) for MUC16 mouse colony development; A5 is a positive cell derived from a SKOV3 cell line stably transfected with MUC16. Figure 9D: Histological analysis of tumors from MUC16:p53+ / - double transgenic mice. Multiple sarcomas and lymphomas were identified in MUC16:p53+ / - double transgenic mice. Sections were stained with hematoxylin and eosin (H&E). Tumors included histiocytic sarcomas of the uterus (I, scale bar: 100 μm), liver (II, scale bar: 50 μm), ovary (III, scale bar: 50 μm), and bone marrow (IV, scale bar: 50 μm), as well as lymphomas of the ovary (V, scale bar: 50 μm), kidney (VI, scale bar: 50 μm), and lung (VII, scale bar: 50 μm), along with carcinoma of the lung (VIII, scale bar: 50 μm). Figure 9E: Cancer-specific Kaplan-Meier survival curves of transgenic mice. MUC16 mice, like wild-type (WT) mice, did not develop spontaneous tumors over the first 18 months. However, when MUC16 mice were crossed with p53 mice, the double transgenic MUC16:p53 mice exhibited significantly worse overall survival compared with either p53 mice (p<0.014) or MUC16 mice due to spontaneous tumor development. [Figure 9D-E]Figures 9A-9E. MUC16 transgenic mice. Figure 9A shows the strategy for constructing the MUC16 conditional construct. The CMV early enhancer plus chicken β-actin promoter (CAG) was used to drive transcription of hrGFP between two loxP sites and downstream MUC16 sequences. Figure 9B: Southern blots show 12 MUC16-positive founder candidates among 99 animals after microinjection. Figure 9C: Western blots with the anti-MUC16 antibody 4H11 identified founders 9 (~50 copies) and 36 (~10 copies) for MUC16 mouse colony development; A5 is a positive cell derived from a SKOV3 cell line stably transfected with MUC16. Figure 9D: Histological analysis of tumors from MUC16:p53+ / - double transgenic mice. Multiple sarcomas and lymphomas were identified in MUC16:p53+ / - double transgenic mice. Sections were stained with hematoxylin and eosin (H&E). Tumors included histiocytic sarcomas of the uterus (I, scale bar: 100 μm), liver (II, scale bar: 50 μm), ovary (III, scale bar: 50 μm), and bone marrow (IV, scale bar: 50 μm), as well as lymphomas of the ovary (V, scale bar: 50 μm), kidney (VI, scale bar: 50 μm), and lung (VII, scale bar: 50 μm), along with carcinoma of the lung (VIII, scale bar: 50 μm). Figure 9E: Cancer-specific Kaplan-Meier survival curves of transgenic mice. MUC16 mice, like wild-type (WT) mice, did not develop spontaneous tumors over the first 18 months. However, when MUC16 mice were crossed with p53 mice, the double transgenic MUC16:p53 mice exhibited significantly worse overall survival compared with either p53 mice (p<0.014) or MUC16 mice due to spontaneous tumor development.

[0173] [Figure 10]Figure 10. Representative histological tissues from 12-month-old male and female MUC16 transgenic mice. Tissue sections were stained with hematoxylin and eosin (H&E, scale bar: 50 μm). Endometrial hyperplasia was observed with similar incidence and severity in both genotypes (only transgenic animals are shown here). The ovaries, lungs, colon, and liver of transgenic animals (Tg) were similar to those of the parental strain (wild type, WT).

[0174] [Figure 11A] Figures 11A-11C. The impact of MUC16 in human ovarian cancer. Figure 11A shows the number of MUC16 transcripts. Figure 11B: The quintile of patients with the highest MUC16 expression, combined with the 18 patients with identified MUC16 mutations, had significantly (p=0.02117) worse survival in Kaplan-Meier analysis compared with patients with lower MUC16 expression. Figure 11C shows the relationship between MUC16 gene alterations and PI3K mutation events in ovarian cancer. [Figure 11B-C] Figures 11A-11C. The impact of MUC16 in human ovarian cancer. Figure 11A shows the number of MUC16 transcripts. Figure 11B: The quintile of patients with the highest MUC16 expression, combined with the 18 patients with identified MUC16 mutations, had significantly (p=0.02117) worse survival in Kaplan-Meier analysis compared with patients with lower MUC16 expression. Figure 11C shows the relationship between MUC16 gene alterations and PI3K mutation events in ovarian cancer.

[0175] [Figure 12A]Figures 12A-12C. Glycosylation requirement for MUC16 Matrigel invasion. Figure 12A shows Matrigel invasion assays of SKOV3 transfected cell lines. phrGFP refers to SKOV3 cells expressing a control vector. MUC16 refers to SKOV3 cells expressing MUC16. N3 refers to SKOV3 cells expressing MUC16-N3. N1-2 refers to SKOV3 cells expressing MUC16-N12. N1-2-3 refers to SKOV3 cells expressing MUC16-N123. MUC16-shControl refers to SKOV3 cells expressing MUC16 and a control shRNA. phrGFPshRNAMGAT population #4 refers to SKOV3 cells expressing a control vector and an shRNA against MGAT5. phrGFP-shRNA LGALS3 population #15 refers to SKOV3 cells expressing a control vector and shRNA against LGALS3. MUC16-shMGAT5 refers to SKOV3 cells expressing MUC16 and shRNA against MGAT5. MUC16-shLGALS3 refers to SKOV3 cells expressing MUC16 and shRNA against LGALS3. Figure 12B shows a Matrigel invasion assay of 3T3 cells expressing a control vector, phrGFP, or the indicated MUC16 constructs. Figure 12C shows tumor growth in athymic nude mice implanted with SKOV3 cells expressing the indicated constructs, as determined by tumor volume. [Figure 12B]Figures 12A-12C. Glycosylation requirement for MUC16 Matrigel invasion. Figure 12A shows Matrigel invasion assays of SKOV3 transfected cell lines. phrGFP refers to SKOV3 cells expressing a control vector. MUC16 refers to SKOV3 cells expressing MUC16. N3 refers to SKOV3 cells expressing MUC16-N3. N1-2 refers to SKOV3 cells expressing MUC16-N12. N1-2-3 refers to SKOV3 cells expressing MUC16-N123. MUC16-shControl refers to SKOV3 cells expressing MUC16 and a control shRNA. phrGFPshRNAMGAT population #4 refers to SKOV3 cells expressing a control vector and an shRNA against MGAT5. phrGFP-shRNA LGALS3 population #15 refers to SKOV3 cells expressing a control vector and shRNA against LGALS3. MUC16-shMGAT5 refers to SKOV3 cells expressing MUC16 and shRNA against MGAT5. MUC16-shLGALS3 refers to SKOV3 cells expressing MUC16 and shRNA against LGALS3. Figure 12B shows a Matrigel invasion assay of 3T3 cells expressing a control vector, phrGFP, or the indicated MUC16 constructs. Figure 12C shows tumor growth in athymic nude mice implanted with SKOV3 cells expressing the indicated constructs, as determined by tumor volume. [Figure 12C]Figures 12A-12C. Glycosylation requirement for MUC16 Matrigel invasion. Figure 12A shows Matrigel invasion assays of SKOV3 transfected cell lines. phrGFP refers to SKOV3 cells expressing a control vector. MUC16 refers to SKOV3 cells expressing MUC16. N3 refers to SKOV3 cells expressing MUC16-N3. N1-2 refers to SKOV3 cells expressing MUC16-N12. N1-2-3 refers to SKOV3 cells expressing MUC16-N123. MUC16-shControl refers to SKOV3 cells expressing MUC16 and a control shRNA. phrGFPshRNAMGAT population #4 refers to SKOV3 cells expressing a control vector and an shRNA against MGAT5. phrGFP-shRNA LGALS3 population #15 refers to SKOV3 cells expressing a control vector and shRNA against LGALS3. MUC16-shMGAT5 refers to SKOV3 cells expressing MUC16 and shRNA against MGAT5. MUC16-shLGALS3 refers to SKOV3 cells expressing MUC16 and shRNA against LGALS3. Figure 12B shows a Matrigel invasion assay of 3T3 cells expressing a control vector, phrGFP, or the indicated MUC16 constructs. Figure 12C shows tumor growth in athymic nude mice implanted with SKOV3 cells expressing the indicated constructs, as determined by tumor volume.

[0176] [Figure 13A]Figures 13A-13D. MUC16 glycosylation patterns and peptides. Figure 13A shows N-linked profiling of SKOV3 cells expressing MUC16. Triangles represent fucose. Squares represent N-acetylglucosamine. Grey circles represent mannose. Open circles represent galactose. Diamonds represent N-acetylneuraminic acid. Figure 13B shows a 55-mer (SEQ ID NO: 129) immunogen. Figure 13C shows a 15-mer (SEQ ID NO: 131) immunogen. Figure 13D shows an 18-mer (SEQ ID NO: 130) immunogen. [Figure 13B-D] Figures 13A-13D. MUC16 glycosylation patterns and peptides. Figure 13A shows N-linked profiling of SKOV3 cells expressing MUC16. Triangles represent fucose. Squares represent N-acetylglucosamine. Grey circles represent mannose. Open circles represent galactose. Diamonds represent N-acetylneuraminic acid. Figure 13B shows a 55-mer (SEQ ID NO: 129) immunogen. Figure 13C shows a 15-mer (SEQ ID NO: 131) immunogen. Figure 13D shows an 18-mer (SEQ ID NO: 130) immunogen.

[0177] [Figure 14] Figure 14 provides a detailed ELISA analysis of the relative reactivity of bioreactive supernatants containing MUC16 glycosylated antibodies with both 15-mer and 18-mer glycosylated and non-glycosylated antigens used as immunogens and screening antigen targets.

[0178] [Figure 15A]Figures 15A-15B. MUC16 glycosylation antibodies inhibit Matrigel invasion. Figure 15A shows Matrigel invasion of SKOV3 cells expressing phrGFP control vector or MUC16 in the presence or absence of bioreactive supernatant from the generation of MUC16 glycosylation antibodies. The bar is a reference line representing a relative count of 200. Figure 15B shows Matrigel invasion of SKOV3 cells expressing phrGFP control vector or MUC16 in the presence or absence of purified MUC16 glycosylation antibodies. The bar is a reference line representing a relative count of 90. [Figure 15B] Figures 15A-15B. MUC16 glycosylation antibodies inhibit Matrigel invasion. Figure 15A shows Matrigel invasion of SKOV3 cells expressing phrGFP control vector or MUC16 in the presence or absence of bioreactive supernatant from the generation of MUC16 glycosylation antibodies. The bar is a reference line representing a relative count of 200. Figure 15B shows Matrigel invasion of SKOV3 cells expressing phrGFP control vector or MUC16 in the presence or absence of purified MUC16 glycosylation antibodies. The bar is a reference line representing a relative count of 90.

[0179] [Figure 16A]Figures 16A-16E. MUC16 glycosylation antibodies inhibit Matrigel invasion. Figure 16A shows Matrigel invasion of SKOV3 cells expressing phrGFP control vector or the indicated MUC16 constructs in the presence of (i) control antibody; (ii) 4H11; or (iii) MUC16 glycosylation antibody clone 10C6.E4. Figure 16B shows Matrigel invasion of SKOV3 cells stably expressing phrGFP control vector or the indicated MUC16 constructs after a third round of FACs sorting with 4H11 in the presence of (i) control antibody; (ii) 4H11; or (iii) MUC16 glycosylation antibody clone 10C6.E4. Figure 16C shows Matrigel invasion of 3T3 cells expressing the phrGFP control vector or the indicated MUC16 constructs in the presence of (i) a control antibody; (ii) 4H11; or (iii) the MUC16 glycosylation antibody clone 10C6.E4. Figure 16D shows tumor growth, as indicated by tumor volume, in athymic nude mice implanted with SKOV3 cells expressing MUC16 and either mock-treated (MUC16) or treated with the MUC16 glycosylation antibody 10C6.E4 (MUC16+10C6.E4). Arrows indicate the days on which 100 μg of the MUC16 glycosylation antibody was administered. Figure 16E shows staining of human ovarian tumor samples with the indicated antibodies. [Figure 16B]Figures 16A-16E. MUC16 glycosylation antibodies inhibit Matrigel invasion. Figure 16A shows Matrigel invasion of SKOV3 cells expressing phrGFP control vector or the indicated MUC16 constructs in the presence of (i) control antibody; (ii) 4H11; or (iii) MUC16 glycosylation antibody clone 10C6.E4. Figure 16B shows Matrigel invasion of SKOV3 cells stably expressing phrGFP control vector or the indicated MUC16 constructs after a third round of FACs sorting with 4H11 in the presence of (i) control antibody; (ii) 4H11; or (iii) MUC16 glycosylation antibody clone 10C6.E4. Figure 16C shows Matrigel invasion of 3T3 cells expressing the phrGFP control vector or the indicated MUC16 constructs in the presence of (i) a control antibody; (ii) 4H11; or (iii) the MUC16 glycosylation antibody clone 10C6.E4. Figure 16D shows tumor growth, as indicated by tumor volume, in athymic nude mice implanted with SKOV3 cells expressing MUC16 and either mock-treated (MUC16) or treated with the MUC16 glycosylation antibody 10C6.E4 (MUC16+10C6.E4). Arrows indicate the days on which 100 μg of the MUC16 glycosylation antibody was administered. Figure 16E shows staining of human ovarian tumor samples with the indicated antibodies. [Figure 16C]Figures 16A-16E. MUC16 glycosylation antibodies inhibit Matrigel invasion. Figure 16A shows Matrigel invasion of SKOV3 cells expressing phrGFP control vector or the indicated MUC16 constructs in the presence of (i) control antibody; (ii) 4H11; or (iii) MUC16 glycosylation antibody clone 10C6.E4. Figure 16B shows Matrigel invasion of SKOV3 cells stably expressing phrGFP control vector or the indicated MUC16 constructs after a third round of FACs sorting with 4H11 in the presence of (i) control antibody; (ii) 4H11; or (iii) MUC16 glycosylation antibody clone 10C6.E4. Figure 16C shows Matrigel invasion of 3T3 cells expressing the phrGFP control vector or the indicated MUC16 constructs in the presence of (i) a control antibody; (ii) 4H11; or (iii) the MUC16 glycosylation antibody clone 10C6.E4. Figure 16D shows tumor growth, as indicated by tumor volume, in athymic nude mice implanted with SKOV3 cells expressing MUC16 and either mock-treated (MUC16) or treated with the MUC16 glycosylation antibody 10C6.E4 (MUC16+10C6.E4). Arrows indicate the days on which 100 μg of the MUC16 glycosylation antibody was administered. Figure 16E shows staining of human ovarian tumor samples with the indicated antibodies. [Figure 16D]Figures 16A-16E. MUC16 glycosylation antibodies inhibit Matrigel invasion. Figure 16A shows Matrigel invasion of SKOV3 cells expressing phrGFP control vector or the indicated MUC16 constructs in the presence of (i) control antibody; (ii) 4H11; or (iii) MUC16 glycosylation antibody clone 10C6.E4. Figure 16B shows Matrigel invasion of SKOV3 cells stably expressing phrGFP control vector or the indicated MUC16 constructs after a third round of FACs sorting with 4H11 in the presence of (i) control antibody; (ii) 4H11; or (iii) MUC16 glycosylation antibody clone 10C6.E4. Figure 16C shows Matrigel invasion of 3T3 cells expressing the phrGFP control vector or the indicated MUC16 constructs in the presence of (i) a control antibody; (ii) 4H11; or (iii) the MUC16 glycosylation antibody clone 10C6.E4. Figure 16D shows tumor growth, as indicated by tumor volume, in athymic nude mice implanted with SKOV3 cells expressing MUC16 and either mock-treated (MUC16) or treated with the MUC16 glycosylation antibody 10C6.E4 (MUC16+10C6.E4). Arrows indicate the days on which 100 μg of the MUC16 glycosylation antibody was administered. Figure 16E shows staining of human ovarian tumor samples with the indicated antibodies. [Figure 16E]Figures 16A-16E. MUC16 glycosylation antibodies inhibit Matrigel invasion. Figure 16A shows Matrigel invasion of SKOV3 cells expressing phrGFP control vector or the indicated MUC16 constructs in the presence of (i) control antibody; (ii) 4H11; or (iii) MUC16 glycosylation antibody clone 10C6.E4. Figure 16B shows Matrigel invasion of SKOV3 cells stably expressing phrGFP control vector or the indicated MUC16 constructs after a third round of FACs sorting with 4H11 in the presence of (i) control antibody; (ii) 4H11; or (iii) MUC16 glycosylation antibody clone 10C6.E4. Figure 16C shows Matrigel invasion of 3T3 cells expressing the phrGFP control vector or the indicated MUC16 constructs in the presence of (i) a control antibody; (ii) 4H11; or (iii) the MUC16 glycosylation antibody clone 10C6.E4. Figure 16D shows tumor growth, as indicated by tumor volume, in athymic nude mice implanted with SKOV3 cells expressing MUC16 and either mock-treated (MUC16) or treated with the MUC16 glycosylation antibody 10C6.E4 (MUC16+10C6.E4). Arrows indicate the days on which 100 μg of the MUC16 glycosylation antibody was administered. Figure 16E shows staining of human ovarian tumor samples with the indicated antibodies.

[0180] [Figure 17] FIG. 17 shows the percentage of cells that internalize labeled MUC16 glycosylated antibodies at the indicated temperatures and time points.

[0181] [Figure 18]Figure 18A shows in vitro growth curves of MUC16 transfectants. 1,000 SKOV3 cells / well in a 96-well flat-bottom plate were cultured with a phrGFP vector control, a phrGFP vector expressing MUC16 (SEQ ID NO: 133), or a phrGFP vector expressing MUC16 (SEQ ID NO: 132) and incubated at 37°C and 5% CO for 5 days. Each day, plates were stained with AlamarBlue and incubated at 37°C and 5% CO for 4 hours. Plates were read using a CytoFluor Fluorescent plate reader. No significant differences were observed among the curves. Figure 18B shows Matrigel invasion assays of SKOV3 phrGFP, SKOV3 MUC16-GFP, or SKOV3-MUC16-GFP cells. Each assay was performed at least twice in triplicate and counted manually. Results are expressed as the relative number of invading cells. The differences in c114 and c344 tumors were statistically significant compared to phrGFP. Figure 18C shows SKOV3 transfectant tumor growth in athymic female nude mice. Two million tumor cells were introduced into the flanks of 10 nu / nu mice, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. The difference in mean tumor volume was statistically significantly greater for mice bearing MUC16 tumors (p<0.0001) and MUC16 tumors (p=0.002) compared to phrGFP tumors. Abbreviations in Figures 18A-C: "SKOV3phrGFP" and "phrGFP" refer to SKOV3 cells expressing the control phrGFP vector; "SKOV3MUC16-GFP" and "c114" refer to SKOV3 cells expressing MUC16 (SEQ ID NO: 133); "SKOV3MUC16-GFP" and "c344" refer to SKOV3 cells expressing MUC16 (SEQ ID NO: 132).

[0182] [Figure 19A]Figures 19A-19F show the effect of MUC16 expression on SKOV3 ovarian cancer cells. Figure 19A shows a Matrigel invasion assay of SKOV3 cells expressing a control phrGFP control vector ("phrGFP") or a phrGFP vector expressing MUC16 (SEQ ID NO: 133; "c114") treated with or without: (1) 5 μg / mL tunicamycin; (2) 5 μg / mL control pFUSE protein; (3) 5 μg / mL MUC16-pFUSE fusion protein; or (4) 5 μg / mL 117-244LGALS3-pFUSE fusion protein. Results are expressed as the relative number of invasive cells 48 hours after treatment. c114 cells were more invasive than phrGFP cells (p<0.0001). The invasive properties of c114 cells were not affected by treatment with the pFUSE vector protein alone. Treatment with tunicamycin (an N-glycosylation inhibitor) reduced the invasive properties of c114 cells. Treatment with MUC16-pFUSE fusion protein or 117-244LGALS3-pFUSE reduced the invasive properties of c114 cells (p<0.0001). Figure 19B shows a Matrigel invasion assay of SKOV3 cells transfected with phrGFP vector control ("phrGFP") or phrGFP vector expressing MUC16 (SEQ ID NO: 133) ("c114") in the presence or absence of lamelli control shRNA, MGAT5-specific shRNA, or LGALS3-specific shRNA. c114 cells treated with MGAT5-specific or LGALS3-specific shRNAs showed reduced invasion compared to phrGFP cells treated with these shRNAs. Control shRNAs had no effect on c114 cell invasion. Each assay was performed more than twice in triplicate and counted manually. Figure 19C shows the glycosylation-dependence of SKOV3-MUC16 Matrigel invasion.SKOV3 cells were transfected with a phrGFP control vector or phrGFP vectors expressing the following MUC16 mutants: c114 (SEQ ID NO: 133), N1mut c114 (SEQ ID NO: 151), N24 muc c114 (SEQ ID NO: 152), N30mut c114 (SEQ ID NO: 139), N1-N24 mut c114 (SEQ ID NO: 153), and N1-N24-N30mut c114 (SEQ ID NO: 154). c114-expressing cells exhibited increased invasion compared to control phrGFP cells. The increased invasive properties of c114-expressing cells were dependent on N-glycosylation of asparagine at amino acid positions 24 and 30 of MUC16 c114 (SEQ ID NO: 133). While both the N24 and N30 sites were important, the N30 position appeared to be more important than the N24 site for this effect. Each assay was performed at least twice in triplicate and counted manually. Results are expressed as a percentage compared to the phrGFP vector control. Figure 19D shows the glycosylation dependence of SKOV3-MUC16 Matrigel invasion. SKOV3 cells were transfected with a phrGFP control vector or a phrGFP vector expressing the following MUC16 mutants: c344 (SEQ ID NO: 132), N24mut c344 (SEQ ID NO: 173), N30mut c344 (SEQ ID NO: 174), or N24-N30mut c344 (SEQ ID NO: 175). c344-expressing cells showed increased invasion compared to control phrGFP cells. The increased invasive properties of c344-expressing cells were dependent on N-glycosylation of the asparagines corresponding to amino acid positions 24 and 30 of MUC16 (SEQ ID NO: 133). Each assay was performed more than twice in triplicate and counted manually. Figure 19E shows the effect of MUC16 expression on selected signaling pathways.SKOV3 cells transfected with MUC16 (SEQ ID NO: 133) were treated with or without control shRNA ("shLamelli"), shRNA against MGAT5 ("shMGAT5"), or shRNA against LGALS3 ("shLGALLS3"), and compared with SKOV3 cells transfected with phrGFP vector control ("phrGFP") or phrGFP vector expressing MUC16-N30mut (SEQ ID NO: 139) ("N30mut"). Cells were examined for activation of pAKT, pERK1 / 2, pSRC, and pEGF receptor (pEGFR) signaling pathways. Phosphorylation of AKT (S473) and ERK1 / 2 (pT202 / Y204) was increased in MUC16 cells. Knockdown of MGAT5 (shMGAT5), knockdown of galectin-3 (shLGALLS3), and the N30A mutation each reduced MUC16-induced oncogene activation in the SKOV3 cell line. Figure 19F shows SKOV3 transfectant tumor growth in athymic female nude mice. Two million tumor cells (described below) were introduced into the flanks of 10 nu / nu mice for each condition, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. In vivo growth of c114 tumor cells was significantly more aggressive than that of phrGFP tumor cells (p<0.0001). N1-N24-N30-mutc114, c114-sh-MGAT5, and c114-sh-LGALS3 tumor cells did not exhibit enhanced growth compared to phrGFP tumor cells.Description of tumor cells: "phrGFP" refers to SKOV3 cells transfected with a phrGFP vector control; "c114" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16 (SEQ ID NO: 133); "N1-N24-N30-mutc114" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16-N1-N24-N30-mut (SEQ ID NO: 154). "c114-sh-MGAT5" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16 (SEQ ID NO: 133) and treated with shRNA against MGAT5; and "c114-sh-LGALS3" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16 (SEQ ID NO: 133) and treated with shRNA against LGALS3. [Figure 19B-D]Figures 19A-19F show the effect of MUC16 expression on SKOV3 ovarian cancer cells. Figure 19A shows a Matrigel invasion assay of SKOV3 cells expressing a control phrGFP control vector ("phrGFP") or a phrGFP vector expressing MUC16 (SEQ ID NO: 133; "c114") treated with or without: (1) 5 μg / mL tunicamycin; (2) 5 μg / mL control pFUSE protein; (3) 5 μg / mL MUC16-pFUSE fusion protein; or (4) 5 μg / mL 117-244LGALS3-pFUSE fusion protein. Results are expressed as the relative number of invasive cells 48 hours after treatment. c114 cells were more invasive than phrGFP cells (p<0.0001). The invasive properties of c114 cells were not affected by treatment with the pFUSE vector protein alone. Treatment with tunicamycin (an N-glycosylation inhibitor) reduced the invasive properties of c114 cells. Treatment with MUC16-pFUSE fusion protein or 117-244LGALS3-pFUSE reduced the invasive properties of c114 cells (p<0.0001). Figure 19B shows a Matrigel invasion assay of SKOV3 cells transfected with phrGFP vector control ("phrGFP") or phrGFP vector expressing MUC16 (SEQ ID NO: 133) ("c114") in the presence or absence of lamelli control shRNA, MGAT5-specific shRNA, or LGALS3-specific shRNA. c114 cells treated with MGAT5-specific or LGALS3-specific shRNAs showed reduced invasion compared to phrGFP cells treated with these shRNAs. Control shRNAs had no effect on c114 cell invasion. Each assay was performed more than twice in triplicate and counted manually. Figure 19C shows the glycosylation-dependence of SKOV3-MUC16 Matrigel invasion.SKOV3 cells were transfected with a phrGFP control vector or phrGFP vectors expressing the following MUC16 mutants: c114 (SEQ ID NO: 133), N1mut c114 (SEQ ID NO: 151), N24 muc c114 (SEQ ID NO: 152), N30mut c114 (SEQ ID NO: 139), N1-N24 mut c114 (SEQ ID NO: 153), and N1-N24-N30mut c114 (SEQ ID NO: 154). c114-expressing cells exhibited increased invasion compared to control phrGFP cells. The increased invasive properties of c114-expressing cells were dependent on N-glycosylation of asparagine at amino acid positions 24 and 30 of MUC16 c114 (SEQ ID NO: 133). While both the N24 and N30 sites were important, the N30 position appeared to be more important than the N24 site for this effect. Each assay was performed at least twice in triplicate and counted manually. Results are expressed as a percentage compared to the phrGFP vector control. Figure 19D shows the glycosylation dependence of SKOV3-MUC16 Matrigel invasion. SKOV3 cells were transfected with a phrGFP control vector or a phrGFP vector expressing the following MUC16 mutants: c344 (SEQ ID NO: 132), N24mut c344 (SEQ ID NO: 173), N30mut c344 (SEQ ID NO: 174), or N24-N30mut c344 (SEQ ID NO: 175). c344-expressing cells showed increased invasion compared to control phrGFP cells. The increased invasive properties of c344-expressing cells were dependent on N-glycosylation of the asparagines corresponding to amino acid positions 24 and 30 of MUC16 (SEQ ID NO: 133). Each assay was performed more than twice in triplicate and counted manually. Figure 19E shows the effect of MUC16 expression on selected signaling pathways.SKOV3 cells transfected with MUC16 (SEQ ID NO: 133) were treated with or without control shRNA ("shLamelli"), shRNA against MGAT5 ("shMGAT5"), or shRNA against LGALS3 ("shLGALLS3"), and compared with SKOV3 cells transfected with phrGFP vector control ("phrGFP") or phrGFP vector expressing MUC16-N30mut (SEQ ID NO: 139) ("N30mut"). Cells were examined for activation of pAKT, pERK1 / 2, pSRC, and pEGF receptor (pEGFR) signaling pathways. Phosphorylation of AKT (S473) and ERK1 / 2 (pT202 / Y204) was increased in MUC16 cells. Knockdown of MGAT5 (shMGAT5), knockdown of galectin-3 (shLGALLS3), and the N30A mutation each reduced MUC16-induced oncogene activation in the SKOV3 cell line. Figure 19F shows SKOV3 transfectant tumor growth in athymic female nude mice. Two million tumor cells (described below) were introduced into the flanks of 10 nu / nu mice for each condition, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. In vivo growth of c114 tumor cells was significantly more aggressive than that of phrGFP tumor cells (p<0.0001). N1-N24-N30-mutc114, c114-sh-MGAT5, and c114-sh-LGALS3 tumor cells did not exhibit enhanced growth compared to phrGFP tumor cells.Description of tumor cells: "phrGFP" refers to SKOV3 cells transfected with a phrGFP vector control; "c114" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16 (SEQ ID NO: 133); "N1-N24-N30-mutc114" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16-N1-N24-N30-mut (SEQ ID NO: 154). "c114-sh-MGAT5" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16 (SEQ ID NO: 133) and treated with shRNA against MGAT5; and "c114-sh-LGALS3" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16 (SEQ ID NO: 133) and treated with shRNA against LGALS3. [Figure 19E-F]Figures 19A-19F show the effect of MUC16 expression on SKOV3 ovarian cancer cells. Figure 19A shows a Matrigel invasion assay of SKOV3 cells expressing a control phrGFP control vector ("phrGFP") or a phrGFP vector expressing MUC16 (SEQ ID NO: 133; "c114") treated with or without: (1) 5 μg / mL tunicamycin; (2) 5 μg / mL control pFUSE protein; (3) 5 μg / mL MUC16-pFUSE fusion protein; or (4) 5 μg / mL 117-244LGALS3-pFUSE fusion protein. Results are expressed as the relative number of invasive cells 48 hours after treatment. c114 cells were more invasive than phrGFP cells (p<0.0001). The invasive properties of c114 cells were not affected by treatment with the pFUSE vector protein alone. Treatment with tunicamycin (an N-glycosylation inhibitor) reduced the invasive properties of c114 cells. Treatment with MUC16-pFUSE fusion protein or 117-244LGALS3-pFUSE reduced the invasive properties of c114 cells (p<0.0001). Figure 19B shows a Matrigel invasion assay of SKOV3 cells transfected with phrGFP vector control ("phrGFP") or phrGFP vector expressing MUC16 (SEQ ID NO: 133) ("c114") in the presence or absence of lamelli control shRNA, MGAT5-specific shRNA, or LGALS3-specific shRNA. c114 cells treated with MGAT5-specific or LGALS3-specific shRNAs showed reduced invasion compared to phrGFP cells treated with these shRNAs. Control shRNAs had no effect on c114 cell invasion. Each assay was performed more than twice in triplicate and counted manually. Figure 19C shows the glycosylation-dependence of SKOV3-MUC16 Matrigel invasion.SKOV3 cells were transfected with a phrGFP control vector or phrGFP vectors expressing the following MUC16 mutants: c114 (SEQ ID NO: 133), N1mut c114 (SEQ ID NO: 151), N24 muc c114 (SEQ ID NO: 152), N30mut c114 (SEQ ID NO: 139), N1-N24 mut c114 (SEQ ID NO: 153), and N1-N24-N30mut c114 (SEQ ID NO: 154). c114-expressing cells exhibited increased invasion compared to control phrGFP cells. The increased invasive properties of c114-expressing cells were dependent on N-glycosylation of asparagine at amino acid positions 24 and 30 of MUC16 c114 (SEQ ID NO: 133). While both the N24 and N30 sites were important, the N30 position appeared to be more important than the N24 site for this effect. Each assay was performed at least twice in triplicate and counted manually. Results are expressed as a percentage compared to the phrGFP vector control. Figure 19D shows the glycosylation dependence of SKOV3-MUC16 Matrigel invasion. SKOV3 cells were transfected with a phrGFP control vector or a phrGFP vector expressing the following MUC16 mutants: c344 (SEQ ID NO: 132), N24mut c344 (SEQ ID NO: 173), N30mut c344 (SEQ ID NO: 174), or N24-N30mut c344 (SEQ ID NO: 175). c344-expressing cells showed increased invasion compared to control phrGFP cells. The increased invasive properties of c344-expressing cells were dependent on N-glycosylation of the asparagines corresponding to amino acid positions 24 and 30 of MUC16 (SEQ ID NO: 133). Each assay was performed more than twice in triplicate and counted manually. Figure 19E shows the effect of MUC16 expression on selected signaling pathways.SKOV3 cells transfected with MUC16 (SEQ ID NO: 133) were treated with or without control shRNA ("shLamelli"), shRNA against MGAT5 ("shMGAT5"), or shRNA against LGALS3 ("shLGALLS3"), and compared with SKOV3 cells transfected with phrGFP vector control ("phrGFP") or phrGFP vector expressing MUC16-N30mut (SEQ ID NO: 139) ("N30mut"). Cells were examined for activation of pAKT, pERK1 / 2, pSRC, and pEGF receptor (pEGFR) signaling pathways. Phosphorylation of AKT (S473) and ERK1 / 2 (pT202 / Y204) was increased in MUC16 cells. Knockdown of MGAT5 (shMGAT5), knockdown of galectin-3 (shLGALLS3), and the N30A mutation each reduced MUC16-induced oncogene activation in the SKOV3 cell line. Figure 19F shows SKOV3 transfectant tumor growth in athymic female nude mice. Two million tumor cells (described below) were introduced into the flanks of 10 nu / nu mice for each condition, and the mice were observed for tumor formation. Tumors were measured twice weekly with calipers. In vivo growth of c114 tumor cells was significantly more aggressive than that of phrGFP tumor cells (p<0.0001). N1-N24-N30-mutc114, c114-sh-MGAT5, and c114-sh-LGALS3 tumor cells did not exhibit enhanced growth compared to phrGFP tumor cells.Description of tumor cells: "phrGFP" refers to SKOV3 cells transfected with a phrGFP vector control; "c114" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16 (SEQ ID NO: 133); "N1-N24-N30-mutc114" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16-N1-N24-N30-mut (SEQ ID NO: 154). "c114-sh-MGAT5" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16 (SEQ ID NO: 133) and treated with shRNA against MGAT5; and "c114-sh-LGALS3" refers to SKOV3 cells transfected with a phrGFP vector expressing MUC16 (SEQ ID NO: 133) and treated with shRNA against LGALS3.

[0183] [Figure 20A-B]Figure 20A shows the effect of MUC16 expression on EGFR surface expression. SKOV3-phrGFP and SKOV3-MUC16 transfectants were examined in the presence or absence of 24-hour cycloheximide (CHX) treatment. Geometric mean fluorescence of EGFR and MUC16 expression at basal and post-CHX treatment levels is shown. EGFR in SKOV3-phrGFP samples decreased to 58% of untreated levels after 24 hours of CHX treatment. Significant MUC16 expression was absent in these cells. In contrast, SKOV3-MUC16 cells showed an approximately 25% increase in EGFR geometric mean fluorescence, which decreased to 83% of the control EGFR geometric mean fluorescence after CHX exposure. The mean fluorescence of MUC16 was not significantly reduced by CHX. Figure 20B shows densitometry of the EGFR / β-actin ratio from a Western blot of whole-cell EGFR, demonstrating a steady loss of EGFR over time in SKOV3-phrGFP cells treated with CHX. In contrast, total levels of EGFR in SKOV3-MUC16 cells were maintained, indicating stabilization of EGFR compared to the MUC16(-) control cell line ("phrGFP(-)"). Figure 20C shows Matrigel invasion assays of SKOV3 cells transfected with the phrGFP control vector ("stable phrGFP"), SKOV3-MUC16, and the SKOV3-MUC16(tet) tetracycline-inducible cell line, expressed as a percentage of control cell invasion. Tetracycline induction of SKOV3-MUC16(tet) cells resulted in an invasive phenotype similar to that of stable SKOV3-MUC16 (SKOV3), whereas uninduced cells were consistent with MUC16-phrGFP control cells. This MUC16-induced increase in Matrigel invasion was completely dependent on EGFR. When EGFR hairpin RNA knockdown (shEGFR) was introduced into SKOV3 cells, tetracycline induced MUC16 expression (4H11-positive protein on Western blot) but did not increase Matrigel invasion. Each assay was performed in triplicate and counted manually.Figure 20D: EGFR stability in MUC16(+) and MUC16(-) cells. Cell extracts from uninduced or tetracycline-induced SKOV3-MUC16(tet) cell lines treated with CHX for 24 hours and assayed for total cellular EGFR are expressed as densitometric ratios and normalized to β-actin. The slope of EGFR reduction in tetracycline-induced SKOV3-MUC16 cells recapitulates the EGFR-stabilizing effect of MUC16 expression compared to the MUC16(-) line. This result is similar to the effect of stable transfection shown in Figure 20B above. [Figure 20C]Figure 20A shows the effect of MUC16 expression on EGFR surface expression. SKOV3-phrGFP and SKOV3-MUC16 transfectants were examined in the presence or absence of 24-hour cycloheximide (CHX) treatment. Geometric mean fluorescence of EGFR and MUC16 expression at basal and post-CHX treatment levels is shown. EGFR in SKOV3-phrGFP samples decreased to 58% of untreated levels after 24 hours of CHX treatment. Significant MUC16 expression was absent in these cells. In contrast, SKOV3-MUC16 cells showed an approximately 25% increase in EGFR geometric mean fluorescence, which decreased to 83% of the control EGFR geometric mean fluorescence after CHX exposure. The mean fluorescence of MUC16 was not significantly reduced by CHX. Figure 20B shows densitometry of the EGFR / β-actin ratio from a Western blot of whole-cell EGFR, demonstrating a steady loss of EGFR over time in SKOV3-phrGFP cells treated with CHX. In contrast, total levels of EGFR in SKOV3-MUC16 cells were ...

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[Claim 1] An antibody or antigen-binding fragment thereof or a method as described in the specification.

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