Antibodies directed against claudin-6, including bispecific formats

Abstract

The present disclosure is directed to antibodies specific for claudin 6 and CD3, and methods for preparing and using the same. The present disclosure describes the isolation and characterization of antibodies, antibody fragments, and antibody variants specific for claudin 6 and CD3.

Description

[Technical Field]

[0001] Related Applications This application claims the benefit of U.S. Provisional Application No. 63 / 385,535 (filed November 30, 2022), U.S. Provisional Application No. 63 / 496,174 (filed April 14, 2023), U.S. Provisional Application No. 63 / 506,533 (filed June 6, 2023), U.S. Provisional Application No. 63 / 517,668 (filed August 4, 2023), and U.S. Provisional Application No. 63 / 591,924 (filed October 20, 2023), each of which is incorporated by reference in its entirety herein.

[0002] The present disclosure is directed to compositions and related methods that bind to claudin-6.

[0003] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in XML format, which is incorporated herein by reference in its entirety. The XML copy (created November 28, 2023) is titled "INM-001PC_122086-5001 Sequence Listing" and is 142,000 bytes in size. [Background technology]

[0004] Cell adhesion proteins are essential for maintaining tissue integrity and regulating various cellular events in a wide variety of physiological and pathological processes. Among cell adhesion proteins, some members of the claudin (CLDN) family are often abnormally expressed in various cancers. The clinical application of CLDN therapeutics has been hindered by the lack of specificity of antibodies for specific CLDN proteins and the widespread expression of closely related CLDN family members in normal cells. Therefore, there remains a great need for improved compositions and methods that can modulate the activity of CLDN family members to treat various cancers and diseases. Summary of the Invention

[0005] Thus, in various aspects, the present disclosure relates to compositions that specifically bind to claudin 6 and CD3. The present disclosure describes the isolation and characterization of antibodies, antibody fragments, and antibody variants specific to claudin 6 and CD3. In some embodiments, the claudin 6 and CD3-specific antibody is a tandem single-chain variable fragment (scFv). In some embodiments, the claudin 6 and CD3-specific antibody is a claudin 6 and CD3-specific scFv-Fab Fc antibody. In some embodiments, the claudin 6 and CD3-specific antibody is a claudin 6 and CD3-specific IgG-(scFv)2 antibody. In some embodiments, the claudin 6 and CD3-specific antibody is a claudin 6 and CD3-specific scFv-Fab Fc antibody. In some embodiments, the claudin 6 and CD3-specific antibody simultaneously binds to claudin 6 and CD3.

[0006] In some embodiments, disclosed herein is a composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, wherein the antibody is (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i.) SEQ ID NO: 80; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or (ii.) SEQ ID NO: 89; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; or (iii.) SEQ ID NO: 90; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 48 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; or (iv.) SEQ ID NO: 91, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 49 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; or (v.) SEQ ID NO: 92, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; or (vi.) SEQ ID NO: 111, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; and (c) a first light chain selected from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; In any of the above sequences, optionally, one or more of the glycine and serine-containing linkers are replaced with another peptide linker or a functionally equivalent variation thereof.

[0007] In some embodiments, the Fc is derived from an IgG.

[0008] In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0009] In some embodiments, antibodies are formed through knobs-in-hole interactions in the Fc region. In some embodiments, the human IgG Fc comprises one or more mutations to promote knobs-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V is selected from.

[0010] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate effector function of the Fc domain, hi some embodiments, the mutations are L234A and L235A (LALA) substitutions in human IgG1.

[0011] In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0012] In some embodiments, disclosed herein is a composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, wherein the antibody is (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: SEQ ID NO: 81, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; and (c) a light chain chosen from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66 an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; In any of the above sequences, optionally, one or more of the glycine and serine-containing linkers are replaced with another peptide linker or a functionally equivalent variation thereof.

[0013] In some embodiments, the Fc is derived from an IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0014] In some embodiments, antibodies are formed through knobs-in-hole interactions in the Fc region. In some embodiments, the human IgG Fc comprises one or more mutations to promote knobs-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V is.

[0015] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate effector function of the Fc domain. In some embodiments, the mutations are L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0016] In some embodiments, disclosed herein is a composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, wherein the antibody is (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i.) SEQ ID NO: 117, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (ii.) SEQ ID NO: 119; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (iii.) SEQ ID NO: 118; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iv.) SEQ ID NO: 120; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; and (c) a light chain chosen from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66 an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; In any of the above sequences, optionally, one or more of the glycine and serine-containing linkers are replaced with another peptide linker or a functionally equivalent variation thereof.

[0017] In some embodiments, the Fc is derived from an IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0018] In some embodiments, antibodies are formed through knobs-in-hole interactions in the Fc region. In some embodiments, the human IgG Fc comprises one or more mutations to promote knobs-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V is.

[0019] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate effector function of the Fc domain. In some embodiments, the mutations are L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0020] In some embodiments, disclosed herein is a composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, wherein the antibody is (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i) SEQ ID NO: 121; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; (ii) SEQ ID NO: 123; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; (iii) SEQ ID NO: 125; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; (iv) SEQ ID NO: 127, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or (v) SEQ ID NO: 129, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; and (c) a first light chain selected from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; and (d) a second light chain selected from: (i) SEQ ID NO: 122; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; or (ii) SEQ ID NO: 124; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; or (iii) SEQ ID NO: 126; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; or (iv) SEQ ID NO: 128, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; or (v) SEQ ID NO: 130, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; In any of the above sequences, optionally, one or more of the glycine and serine-containing linkers are replaced with another peptide linker or a functionally equivalent variation thereof.

[0021] In some embodiments, disclosed herein are bispecific antibodies comprising three polypeptides (e.g., a first polypeptide, a second polypeptide, and a third polypeptide) that form a first antigen-binding domain that binds to CLDN6 and a second antigen-binding domain that binds to CD3. In some embodiments, the first polypeptide comprises a first variable light chain region (first V L ), wherein the first variable light chain region comprises a CDR1 sequence comprising the amino acid sequence of SEQ ID NO: 1, a CDR2 sequence comprising the amino acid sequence of SEQ ID NO: 2, and a CDR3 sequence comprising the amino acid sequence of SEQ ID NO: 3. In some embodiments, the second polypeptide comprises a first light chain comprising a first variable light chain region (first VH In some embodiments, the third polypeptide comprises a first heavy chain and a second light chain, wherein the second heavy chain comprises a second variable heavy chain region (second V) comprising a CDR1 sequence comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 sequence comprising the amino acid sequence of SEQ ID NO: 5, and a CDR3 sequence comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the third polypeptide comprises a second heavy chain and a second light chain, wherein the second heavy chain comprises a second variable heavy chain region (second V) comprising a CDR1 sequence comprising the amino acid sequence of SEQ ID NO: 25, a CDR2 sequence comprising the amino acid sequence of SEQ ID NO: 26, and a CDR3 sequence comprising the amino acid sequence of SEQ ID NO: 27. H ), and the second light chain comprises a second variable light chain region (second V) comprising a CDR1 sequence comprising the amino acid sequence of SEQ ID NO: 28, a CDR2 sequence comprising the amino acid sequence of SEQ ID NO: 29, and a CDR3 sequence comprising the amino acid sequence of SEQ ID NO: 30. L In some embodiments, the second heavy chain and the second light chain are connected by a peptide linker. In some embodiments, the peptide linker is as described herein. In some embodiments, the peptide linker comprises the amino acid sequence of SEQ ID NO: 53 (GKPGSGKPGSGKPGSGKPGS). In some embodiments, the peptide linker comprising one or more glycines and serines is replaced with another peptide linker or a functionally equivalent variation thereof. In some embodiments, the first V L and the first V H interact to form an antigen-binding domain that binds to CLDN6. In some embodiments, the second V L and the second V H interact to form an antigen-binding domain that binds to CD3. In some embodiments, the second V L and the second V H is in scFv format. In some embodiments, the first V L and the first V H is in the Fab format or a fragment thereof.

[0022] In some embodiments, the first variable light chain region of the first polypeptide comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0023] In some embodiments, the first variable heavy chain region of the second polypeptide comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0024] In some embodiments, the second variable heavy chain region of the third polypeptide comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0025] In some embodiments, the second variable light chain region of the third polypeptide comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0026] In some embodiments, the first polypeptide comprising a light chain comprises a first variable light chain region and a light chain constant domain (sometimes referred to as a first light chain constant domain). In some embodiments, the first light chain constant domain comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0027] In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0028] In some embodiments, the second polypeptide comprising the first heavy chain comprises a first variable heavy chain region and a heavy chain constant domain (sometimes referred to as a first heavy chain constant domain). In some embodiments, the first heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0029] In some embodiments, the second polypeptide comprises the amino acid sequence of SEQ ID NO: 79, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0030] In some embodiments, the third polypeptide comprises a constant domain. In some embodiments, the constant domain is attached to the C-terminus of the second variable light chain region. In some embodiments, there is no peptide linker between the C-terminus of the second variable light chain region and the constant domain. In some embodiments, the constant domain present in the third polypeptide comprises the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0031] In some embodiments, the third polypeptide comprises the amino acid sequence of SEQ ID NO: 89, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0032] In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO:67, the second polypeptide comprises the amino acid sequence of SEQ ID NO:79, and the third polypeptide comprises the amino acid sequence of SEQ ID NO:89.

[0033] As used herein, the term constant domain refers to an Fc domain. The constant domains exemplified above are optional embodiments, and other constant domains may be substituted for the constant domains described herein.

[0034] In some embodiments, the Fc is derived from an IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0035] In some embodiments, antibodies are formed through knobs-in-hole interactions in the Fc region. In some embodiments, the human IgG Fc comprises one or more mutations to promote knobs-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V is.

[0036] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate effector function of the Fc domain. In some embodiments, the mutations are L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0037] In some embodiments, the composition simultaneously binds to claudin-6 and CD3.

[0038] In some embodiments, the composition binds to claudin 6 with an affinity of less than 10 nM and with an affinity that is at least 100-fold greater than that of claudin 9, claudin 3, and / or claudin 4.

[0039] In some embodiments, disclosed herein is a pharmaceutical composition comprising the isolated antibody of any one of the preceding embodiments, or a nucleic acid molecule encoding same. In some embodiments, the composition is an injectable pharmaceutical composition. In some embodiments, the composition is sterile. In some embodiments, the composition is pyrogen-free.

[0040] In some embodiments, disclosed herein is a nucleic acid molecule encoding an antibody or amino acid sequence according to any of the preceding embodiments.

[0041] In some embodiments, disclosed herein is a vector comprising the nucleic acid molecule of any of the preceding embodiments.

[0042] In some embodiments, disclosed herein is a cell comprising the nucleic acid molecule of any of the preceding embodiments or the vector of any of the preceding embodiments.

[0043] In some embodiments, disclosed herein is a method for modulating and / or targeting claudin 6 and CD3 in a biological cell, comprising contacting the cell with a composition described in any of the preceding embodiments.

[0044] In some embodiments, disclosed herein is a method for modulating the activity of claudin 6 in a biological cell, comprising contacting a cell that expresses claudin 6 with a composition described in any of the preceding embodiments.

[0045] In some embodiments, disclosed herein is a method for inhibiting the function of claudin 6 in a biological cell, the method comprising contacting a cell expressing claudin 6 with a composition described in any of the preceding embodiments.

[0046] In some embodiments, disclosed herein is a method for treating or preventing cancer, comprising administering to a subject in need thereof an effective amount of the composition of any of the preceding embodiments.

[0047] In some embodiments, disclosed herein is the use of a composition of any of the preceding embodiments for the preparation of a medicament for treating or preventing cancer.

[0048] In some embodiments, disclosed herein is a method for treating cancer, wherein the cancer is selected from the group consisting of basal cell carcinoma, biliary tract cancer, bladder cancer, bone cancer, brain and central nervous system cancer, breast cancer, peritoneal cancer, cervical cancer, choriocarcinoma, colorectal cancer, connective tissue cancer, digestive system cancer, endometrial cancer, esophageal cancer, eye cancer, head and neck cancer, gastric cancer (including gastrointestinal cancer), glioblastoma, liver cancer, hepatocellular carcinoma, intraepithelial neoplasia, kidney cancer or renal carcinoma, laryngeal cancer, leukemia, liver cancer, lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma), melanoma, myeloma, neuroblastoma, oral cancer (lip, tongue, mouth, and pharynx), ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, rectal cancer, respiratory system cancer, salivary gland cancer, sarcoma, skin cancer, squamous cell carcinoma, stomach cancer, testicular cancer, thyroid cancer, uterine or endometrial cancer, urinary system cancer, vulvar cancer, lymphoma (Hodgkin's lymphoma and non-Hodgkin's lymphoma, and B-cell lymphoma) and Meigs syndrome (including low-grade / follicular non-Hodgkin's lymphoma (NHL) (including low-grade / follicular NHL, small lymphocytic (SL) NHL, intermediate-grade / follicular NHL, intermediate-grade diffuse NHL, high-grade immunoblastic NHL, high-grade lymphoblastic NHL, high-grade small non-cleaved cell NHL, bulky mass disease NHL, mantle cell lymphoma, AIDS-related lymphoma, and Waldenstrom's macroglobulinemia), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, chronic myeloblastic leukemia, and other carcinomas and sarcomas, and post-transplant lymphoproliferative disorder (PTLD), and abnormal blood vessel proliferation associated with nevus syndrome, edema (e.g., associated with brain tumors), and Meigs syndrome.

[0049] In some embodiments, disclosed herein is an isolated antibody comprising one or more of the sequences disclosed herein.

[0050] The details of one or more examples of the present disclosure are set forth in the detailed description below. Other features or advantages of the present disclosure will become apparent from the following drawings, detailed description of several embodiments, and also from the appended claims. Details of the present disclosure are set forth below in the accompanying description. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, exemplary methods and materials are described herein. Other features, objects, and advantages of the present disclosure will become apparent from the description and claims. In this specification and the appended claims, the singular forms "a," "an," and "the" include the plural forms unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. [Brief explanation of the drawings]

[0051] [Figure 1] Images of exemplary bispecific formats are shown, including tandem scFv (left), scFv-Fab IgG (middle), and IgG-(scFv)2 (right). [Figure 2] 1 is an image showing a schematic diagram of the structure of CLDN6 and illustrating some of the challenges in developing antibodies specific to CLDN6. [Figure 3] 1 is a graph of RNA sequencing data showing how claudin 6 is overexpressed in multiple cancers, including ovarian, lung, endometrial, and gastric cancer. [Figure 4] Image showing non-limiting monospecific challenges in developing antibodies specific to claudin 6, because the antibody must recognize a single amino acid side chain at residue 156 of CLDN6 and CLDN9. [Figure 5] 1 is a chart summarizing data for four selected antibodies. [Figure 6] 1 shows graphs and images of quality control data for IMC-16-3 scFv-Fab IgG antibody (SEQ ID NOs: 79, 67, and 89). [Figure 7]1 shows graphs and images of quality control data for IMC-16-15 scFv-Fab IgG antibody (SEQ ID NOs: 114, 65, and 89). [Figure 8] 1 shows graphs and images of quality control data for IMC-21-1 IgG-(scFv)2 antibody (SEQ ID NOs: 86 and 67). [Figure 9] 1 shows graphs and images of quality control data for IMC-2-7 tandem scFv antibody (SEQ ID NO: 95). [Figure 10] Two graphs of target binding data from flow cytometry experiments are shown. The left panel shows target binding data for IMC-16-3 scFv-Fab IgG antibody (circles), IMC-16-15 scFv-Fab IgG antibody (squares), IMC-21-1 IgG-(scFv)2 antibody (triangles), and IMC-2-7 tandem scFv antibody (inverted triangles) to human CLDN6. The right panel shows target binding data for IMC-16-3 scFv-Fab IgG antibody (circles), IMC-16-15 scFv-Fab IgG antibody (squares), IMC-21-1 IgG-(scFv)2 antibody (triangles), and IMC-2-7 tandem scFv antibody (inverted triangles) to human CD3. The table below shows the binding EC50 data for the molecules to CLDN6 and CD3. [Figure 11]Graphs showing parental and benchmark antibody binding data from flow cytometry experiments. (A) Graph showing binding of IM271-1HEP antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). (B) Graph showing binding of IM271-1HHP antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). (C) Graph showing binding of IM271-1HFJ antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). D is a graph showing binding of antibodies to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). [Figure 12] Graphs showing target binding data from flow cytometry experiments. (A) Graph showing binding of IMC-2-7 tandem scFv antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). (B) Graph showing binding of IMC-16-3 scFv-Fab IgG antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). (C) Graph showing binding of IMC-16-15 scFv-Fab IgG antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). D is a graph showing the binding of IMC-21-1 IgG-(scFv)2 antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). [Figure 13]Two graphs of cytotoxicity data from T cell-dependent cytotoxicity experiments are shown. The left panel shows cytotoxicity data for IMC-16-3 scFv-Fab IgG antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, IMC-2-7 tandem scFv antibody, and IMC-16-C2 antibody (negative control) in ovarian cancer OV-90 cells. The right panel shows target binding data for IMC-16-3 scFv-Fab IgG antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, IMC-2-7 tandem scFv antibody, and IMC-16-C2 antibody (negative control) in HEK cells. [Figure 14] 10 is a graph showing cytokine production by human PBMCs cocultured with CLDN6-positive OV-90 cells in the presence or absence of IMC-16-3 scFv-Fab IgG antibody. (A) shows the results for IL-2 production, (B) shows the results for IL-6 production, (C) shows the results for IL-10 production, (D) shows the results for IFN-γ production, and (E) shows the results for TNF-α production. [Figure 15] 1 is a graph showing cytokine production by human PBMCs cocultured with CLDN6-positive OV-90 cells in the presence or absence of IMC-16-15 scFv-Fab IgG. (A) shows the results for IL-2 production, (B) shows the results for IL-6 production, (C) shows the results for IL-10 production, (D) shows the results for IFN-γ production, and (E) shows the results for TNF-α production. [Figure 16] 1 is a graph showing cytokine production by human PBMCs cocultured with CLDN6-positive OV-90 cells in the presence or absence of IMC-21-1 IgG-(scFv)2 antibody. A shows the results for IL-2 production, B shows the results for IL-6 production, C shows the results for IL-10 production, D shows the results for IFN-γ production, and E shows the results for TNF-α production. [Figure 17]1 is a graph showing cytokine production by human PBMCs cocultured with CLDN6-positive OV-90 cells in the presence or absence of IMC-2-7 tandem scFv antibody, where A shows the results for IL-2 production, B shows the results for IL-6 production, C shows the results for IL-10 production, D shows the results for IFN-γ production, and E shows the results for TNF-α production. [Figure 18] This figure shows graphs of cytotoxicity data from T cell-dependent cytotoxicity experiments. Cytotoxicity data for IMC-2-7 tandem scFv antibody, IMC-16-3 scFv-Fab IgG antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, and negative control (CKV063 LALA) in K562 cells are shown. The table on the right shows the EC50 values ​​for cytotoxicity. [Figure 19A] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data for IMC-16-3 scFv-Fab IgG antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 19B] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data for IMC-16-15 scFv-Fab IgG antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 19C] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data for IMC-21-1 IgG-(scFv)2 antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 19D]Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data for the IMC-2-7 tandem scFv antibody at 24 hours are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 19E] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data at 48 hours for IMC-16-3 scFv-Fab IgG antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 19F] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data at 48 hours for IMC-16-15 scFv-Fab IgG antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 19G]

[0023] Figure 1 shows graphs of cytotoxicity and IFN-γ release potency data at 24 and 48 hours from a cytotoxicity experiment. Cytotoxicity and IFN-γ release data at 48 hours for the IMC-21-1 IgG-(scFv)2 antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 19H] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data at 48 hours for the IMC-2-7 tandem scFv antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 20A]

[0023] Figure 1 is a graph showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from a cytotoxicity experiment. Cytotoxicity and IFN-γ release data for IMC-16-7 antibody (SEQ ID NOs: 79, 67, and 91) at 24 hours are shown. CKV063 LALA antibody is the negative control in the experiment. [Figure 20B] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data for the IMC-2-7 tandem scFv antibody at 24 hours are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 20C] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data for IMC-16-3 scFv-Fab IgG antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 20D] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data for IMC-16-15 scFv-Fab IgG antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 20E] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data for IMC-21-1 IgG-(scFv)2 antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 20F] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data at 48 hours for IMC-16-7 antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 20G] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data at 48 hours for the IMC-2-7 tandem scFv antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 20H]Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data at 48 hours for IMC-16-3 scFv-Fab IgG antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 20I] Graphs showing cytotoxicity and IFN-γ release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IFN-γ release data at 48 hours for IMC-16-15 scFv-Fab IgG antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 20J]

[0023] Figure 1 shows graphs of cytotoxicity and IFN-γ release potency data at 24 and 48 hours from a cytotoxicity experiment. Cytotoxicity and IFN-γ release data at 48 hours for the IMC-21-1 IgG-(scFv)2 antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 21A]

[0023] Figure 1 is a graph showing cytotoxicity and IL-2 release potency data at 24 and 48 hours from a cytotoxicity experiment. Cytotoxicity and IL-2 release data for IMC-16-7 antibody (SEQ ID NOs: 79, 67, and 91) at 24 hours are shown. CKV063 LALA antibody is the negative control in the experiment. [Figure 21B] Figure 1 shows graphs of cytotoxicity and IL-2 release potency data at 24 and 48 hours from a cytotoxicity experiment. Cytotoxicity and IL-2 release data for the IMC-2-7 tandem scFv antibody at 24 hours are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 21C] Graphs showing cytotoxicity and IL-2 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-2 release data for IMC-16-3 scFv-Fab IgG antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 21D] Graphs showing cytotoxicity and IL-2 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-2 release data for IMC-16-15 scFv-Fab IgG antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 21E] Graphs showing cytotoxicity and IL-2 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-2 release data for the MC-21-1 antibody at 24 hours are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 21F] 1 is a graph showing cytotoxicity and IL-2 release potency data at 24 and 48 hours from a cytotoxicity experiment. Cytotoxicity and IL-2 release data at 48 hours for the IMC-16-7 antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 21G] Graphs showing cytotoxicity and IL-2 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-2 release data at 48 hours for the IMC-2-7 tandem scFv antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 21H] Graphs showing cytotoxicity and IL-2 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-2 release data at 48 hours for IMC-16-3 scFv-Fab IgG antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 21I] Graphs showing cytotoxicity and IL-2 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-2 release data at 48 hours for IMC-16-15 scFv-Fab IgG antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 21J]Graphs showing cytotoxicity and IL-2 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-2 release data at 48 hours for the IMC-21-1 IgG-(scFv)2 antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 22A] Graphs showing cytotoxicity and IL-10 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-10 release data for IMC-16-7 antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 22B] Graphs showing cytotoxicity and IL-10 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-10 release data for the IMC-2-7 tandem scFv antibody at 24 hours are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 22C] Graphs showing cytotoxicity and IL-10 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-10 release data for IMC-16-3 scFv-Fab IgG antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 22D] Graphs showing cytotoxicity and IL-10 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-10 release data for IMC-16-15 scFv-Fab IgG antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 22E] Graphs showing cytotoxicity and IL-10 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-10 release data for the IMC-21-1 IgG-(scFv)2 antibody at 24 hours are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 22F]Graphs showing cytotoxicity and IL-10 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-10 release data at 48 hours for IMC-16-7 antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 22G] Figure 1 shows graphs of cytotoxicity and IL-10 release potency data at 24 and 48 hours from a cytotoxicity experiment. Cytotoxicity and IL-10 release data at 48 hours for the IMC-2-7 tandem scFv antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 22H] Graphs showing cytotoxicity and IL-10 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-10 release data at 48 hours for IMC-16-3 scFv-Fab IgG antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 22I] Graphs showing cytotoxicity and IL-10 release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and IL-10 release data at 48 hours for IMC-16-15 scFv-Fab IgG antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 22J] Figure 1 shows graphs of cytotoxicity and IL-10 release potency data at 24 and 48 hours from a cytotoxicity experiment. Cytotoxicity and IL-10 release data at 48 hours for the IMC-21-1 IgG-(scFv)2 antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 23A] Graphs showing cytotoxicity and TNF-α release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and TNF-α release data for IMC-16-7 antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 23B]Graphs showing cytotoxicity and TNF-α release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and TNF-α release data for the IMC-2-7 tandem scFv antibody at 24 hours are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 23C] Graphs showing cytotoxicity and TNF-α release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and TNF-α release data for IMC-16-3 scFv-Fab IgG antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 23D] Graphs showing cytotoxicity and TNF-α release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and TNF-α release data for IMC-16-15 scFv-Fab IgG antibody at 24 hours are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 23E] Figure 1 shows graphs of cytotoxicity and TNF-α release potency data at 24 and 48 hours from a cytotoxicity experiment. Cytotoxicity and TNF-α release data for the IMC-21-1 IgG-(scFv)2 antibody at 24 hours are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 23F] Graphs showing cytotoxicity and TNF-α release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and TNF-α release data at 48 hours for IMC-16-7 antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 23G] Graphs showing cytotoxicity and TNF-α release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and TNF-α release data at 48 hours for the IMC-2-7 tandem scFv antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 23H]Graphs showing cytotoxicity and TNF-α release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and TNF-α release data at 48 hours for IMC-16-3 scFv-Fab IgG antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 23I] Graphs showing cytotoxicity and TNF-α release potency data at 24 and 48 hours from cytotoxicity experiments. Cytotoxicity and TNF-α release data at 48 hours for IMC-16-15 scFv-Fab IgG antibody are shown. CKV063 LALA antibody was the negative control in the experiment. [Figure 23J] Figure 1 shows graphs of cytotoxicity and TNF-α release potency data at 24 and 48 hours from a cytotoxicity experiment. Cytotoxicity and TNF-α release data at 48 hours for the IMC-21-1 IgG-(scFv)2 antibody are shown. The CKV063 LALA antibody was the negative control in the experiment. [Figure 24]Figure 1 shows graphs depicting cytokine analysis of IFN-γ and IL-2 at 24 and 48 hours. Figure 1A shows graphs depicting IFN-γ levels for IMC-2-7 tandem scFv antibody at 24 and 48 hours. Figure 1B shows graphs depicting IFN-γ levels for IMC-16-3 scFv-Fab IgG antibody at 24 and 48 hours. Figure 1C shows graphs depicting IFN-γ levels for IMC-16-15 scFv-Fab IgG antibody at 24 and 48 hours. Figure 1D shows graphs depicting IFN-γ levels for IMC-21-1 IgG-(scFv)2 antibody at 24 and 48 hours. Figure 1E shows graphs depicting IL-2 levels for IMC-2-7 tandem scFv antibody at 24 and 48 hours. F is a graph showing IL-2 levels at 24 and 48 hours for the IMC-16-3 scFv-Fab IgG antibody, G is a graph showing IL-2 levels at 24 and 48 hours for the IMC-16-15 scFv-Fab IgG antibody, and H is a graph showing IL-2 levels at 24 and 48 hours for the IMC-21-1 IgG-(scFv)2 antibody. [Figure 25]Figure 1 shows graphs depicting cytokine analysis of IL-10 and TNF-α at 24 and 48 hours. Figure 1A shows graphs depicting IL-10 levels for IMC-16-7 antibody at 24 and 48 hours. Figure 1B shows graphs depicting IL-10 levels for IMC-2-7 tandem scFv antibody at 24 and 48 hours. Figure 1C shows graphs depicting IL-10 levels for IMC-16-3 scFv-Fab IgG antibody at 24 and 48 hours. Figure 1D shows graphs depicting IL-10 levels for IMC-16-15 scFv-Fab IgG antibody at 24 and 48 hours. Figure 1E shows graphs depicting IL-10 levels for IMC-21-1 IgG-(scFv)2 antibody at 24 and 48 hours. Figure 1F shows graphs depicting TNF-α levels for IMC-16-7 antibody at 24 and 48 hours. G is a graph showing TNF-α levels at 24 and 48 hours for the IMC-2-7 tandem scFv antibody. H is a graph showing TNF-α levels at 24 and 48 hours for the IMC-16-3 scFv-Fab IgG antibody. I is a graph showing TNF-α levels at 24 and 48 hours for the IMC-16-15 scFv-Fab IgG antibody. J is a graph showing TNF-α levels at 24 and 48 hours for the IMC-21-1 IgG-(scFv)2 antibody. [Figure 26]1 is a graph showing the production of TNF-α by human PBMCs co-cultured with either claudin-6-expressing HEK cells or OV-90 cells. A shows antibody-induced TNF-α levels in PBMC:HEK-CLDN6 cocultures for IMC-16-13 scFv-Fab IgG antibody (SEQ ID NOs: 114, 65, and 80), IMC-16-15 scFv-Fab IgG antibody, IMC-16-3 scFv-Fab IgG antibody, IMC-2-7 tandem scFv antibody, IMC-2-13 tandem scFv antibody (SEQ ID NO: 115), IMC-20-13 IgG-scFv antibody (SEQ ID NOs: 114, 65, and 116), IMC-21-1 IgG-(scFv)2 antibody, IMC-21-6 IgG-(scFv)2 antibody (SEQ ID NOs: 104 and 66), and IMC-2-3 tandem scFv antibody (SEQ ID NO: 84). (B) Antibody-induced TNF-α levels in PBMC:OV-90 cocultures for IMC-16-13 scFv-Fab IgG, IMC-16-15 scFv-Fab IgG, IMC-16-3 scFv-Fab IgG, IMC-2-7 tandem scFv, IMC-2-13 tandem scFv, IMC-20-13 IgG-scFv, IMC-21-1 IgG-(scFv)2, IMC-21-6 IgG-(scFv)2, and IMC-2-3 tandem scFv. [Figure 27]10A-10C are graphs showing IFN-γ production by human PBMCs cocultured with either claudin 6-expressing HEK cells or OV-90 cells. (A) shows antibody-induced IFN-γ levels for IMC-16-13 scFv-Fab IgG, IMC-16-15 scFv-Fab IgG, IMC-16-3 scFv-Fab IgG, IMC-2-7 tandem scFv, IMC-2-13 tandem scFv, IMC-20-13 IgG-scFv, IMC-21-1 IgG-(scFv)2, IMC-21-6 IgG-(scFv)2, and IMC-2-3 tandem scFv in PBMC:HEK-CLDN6 cocultures. (B) Antibody-induced IFN-γ levels in PBMC OV-90 cocultures for IMC-16-13 scFv-Fab IgG, IMC-16-15 scFv-Fab IgG, IMC-16-3 scFv-Fab IgG, IMC-2-7 tandem scFv, IMC-2-13 tandem scFv, IMC-20-13 IgG-scFv, IMC-21-1 IgG-(scFv)2, IMC-21-6 IgG-(scFv)2, and IMC-2-3 tandem scFv. [Figure 28]Graphs showing the production of IL-2 (A) and IL-6 (B) levels by human PBMCs cocultured with OV-90 cells. (A) Antibody-induced IL-2 levels in PBMC:OV-90 cocultures for IMC-16-13 scFv-Fab IgG, IMC-16-15 scFv-Fab IgG, IMC-16-3 scFv-Fab IgG, IMC-2-7 tandem scFv, IMC-2-13 tandem scFv, IMC-20-13 IgG-scFv, IMC-21-1 IgG-(scFv)2, IMC-21-6 IgG-(scFv)2, and IMC-2-3 tandem scFv. (B) Antibody-induced IL-6 levels in PBMC OV-90 cocultures for IMC-16-13 scFv-Fab IgG, IMC-16-15 scFv-Fab IgG, IMC-16-3 scFv-Fab IgG, IMC-2-7 tandem scFv, IMC-2-13 tandem scFv, IMC-20-13 IgG-scFv, IMC-21-1 IgG-(scFv)2, IMC-21-6 IgG-(scFv)2, and IMC-2-3 tandem scFv. [Figure 29] 10 is a graph showing the binding affinity of IMC-16-3 scFv-Fab IgG antibody (A), IMC-16-15 scFv-Fab IgG antibody (B), IMC-21-1 IgG-(scFv)2 antibody (C), and IMC-2-7 tandem scFv antibody (D) to hsCD3δε-biotin. [Figure 30]Figure 1 shows graphs of cytotoxicity data from human T cell-dependent cytotoxicity experiments. (A) Cytotoxicity data for IMC-16-3 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-2-7 tandem scFv antibody, and negative control (CKV063 LALA) against K562 CLDN6-expressing cells. (B) Cytotoxicity data for IMC-16-3 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-2-7 tandem scFv antibody, and negative control (CKV063 LALA) against OV-90 cells. [Figure 31] Experiments A and B show cytokine analysis data for the IMC-16-3 scFv-Fab IgG antibody (A) and the IMC-2-7 tandem scFv antibody (B) by human T cells cocultured with K562 CLDN6-expressing cells. A shows the expression level of TNF-α by human T cells cocultured with K562 CLDN6-expressing cells, and B shows the expression level of IFN-γ by human T cells cocultured with K562 CLDN6-expressing cells. [Figure 32] This is a non-limiting image showing residues important for monoclonal antibody binding identified using a CLDN6 alanine scanning library expressed in HEK-293 T cells. CLDN6 specificity was determined by recognition of the Q156 γ carbon (Figure 4). In the case of CLDN9, the native L156 residue sterically inhibits monoclonal antibody binding. [Figure 33]Graphs showing that the binding of the IMC-16-3 scFv-Fab IgG antibody is highly specific to CLDN6. (A) Binding data for the IMC-16-3 scFv-Fab IgG antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, and IMC-2-7 tandem scFv antibody to HEK293-F cells transiently expressing CLDN6. (B) Binding data for the IMC-16-3 scFv-Fab IgG antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, and IMC-2-7 tandem scFv antibody to HEK293-F cells transiently expressing CLDN9. [Figure 34] 1 is a graph showing the specific cytotoxicity mediated by the IMC-16-3 scFv-Fab IgG antibody, which is highly selective for CLDN6. [Figure 35] Graphs showing activation of CD4 (B) and CD8 (A) T cells by bispecific antibody IMC-16-3 in the presence of CLDN-6-expressing tumor cells as indicated by expression of activation markers CD69 and CD25 by human cytotoxic T cells (Tc) and human helper cells (Th). [Figure 36] 1 shows the results of a preclinical animal study of OV-90 xenografts treated with physiologically relevant doses of IMC-16-3. [Figure 37] The selectivity of a reference antibody (RefMAB#1, A) and IMC-16-3 (B) for various claudin proteins is shown. [Figure 38] 1 shows the results of internalization evaluation of IMC-16-3 and RefMAB#2. A shows the percentage of antibody internalization in the K562 cell line with high CLDN6 expression. B shows the percentage of antibody internalization in OV-90 cells with moderate CLDN6 expression. [Figure 39A] 1 shows the results of an OVCAR3 xenograft tumor study in mice treated with various concentrations of IMC-16-3. [Figure 39B]A shows the body weight of the mice throughout the test period. [Figure 40] 1 shows plasma levels of IMC-16-3 in the plasma of non-human primates administered various concentrations of antibody. [Figure 41] The comparative selectivity of RefMAB#2 (A), RefMAB#3 (B), and IMC-16-3 (C) against various claudin proteins is shown. [Figure 42] 1 shows the results of a T cell-dependent cytotoxicity assay comparing IMC-16-3 and RefMAB#3. A shows the results using an E:T ratio of 12.5:1. B shows the results using an E:T ratio of 2.5:1. [Figure 43A] 1 shows the results of a comparative PBMC cytokine production assay comparing IMC-16-3 and RefMAB#3. The figure shows IL-6 production. [Figure 43B] 1 shows the results of a comparative PBMC cytokine production assay comparing IMC-16-3 and RefMAB#3. The figure shows IL-2 production. [Figure 43C] 1 shows the results of a comparative PBMC cytokine production assay comparing IMC-16-3 and RefMAB#3. The figure shows TNF-α production. [Figure 43D] 1 shows the results of a comparative PBMC cytokine production assay comparing IMC-16-3 and RefMAB#3. The figure shows IL-8 production. [Figure 44A] 1 shows the results of a comparative K562-CLDN6 killing assay comparing IMC-16-3 and RefMAB#2 in cell lines with varying levels of CLDN6 expression, and in the presence or absence of human PBMCs. This figure shows results for cells expressing high levels of CLDN6. [Figure 44B]1 shows the results of a comparative K562-CLDN6 killing assay comparing IMC-16-3 and RefMAB#2 in cell lines with varying levels of CLDN6 expression, and in the presence or absence of human PBMCs. This figure shows results for cells expressing intermediate levels of CLDN6. [Figure 44C] Figure 1 shows the results of a comparative K562-CLDN6 killing assay comparing IMC-16-3 and RefMAB#2 in cell lines with varying levels of CLDN6 expression, and in the presence or absence of human PBMCs. This figure shows results for cells that do not express CLDN6 (but have a high rate of nonspecific pinocytosis). [Figure 45] 1 shows the pharmacokinetic results of IMC-16-3 in non-human primates administered 0.1 mg / kg or 1 mg / kg of IMC-16-3. DETAILED DESCRIPTION OF THE INVENTION

[0052] The present disclosure is based, in part, on the surprising discovery of antibodies specific for claudin 6 and CD3. The present disclosure describes the isolation and characterization of antibodies, antibody fragments, and antibody variants specific for claudin 6 and CD3. In some embodiments, the antibodies specific for claudin 6 and CD3 are tandem single-chain variable fragments (scFv). In some embodiments, the antibodies specific for claudin 6 and CD3 are scFv-Fab Fc antibodies specific for claudin 6 and CD3. In some embodiments, the antibodies specific for claudin 6 and CD3 are IgG-(scFV)2 antibodies specific for claudin 6 and CD3. In some embodiments, the antibodies specific for claudin 6 and CD3 are scFv-Fab Fc antibodies specific for claudin 6 and CD3. In some embodiments, the antibodies specific for claudin 6 and CD3 bind simultaneously to claudin 6 and CD3.

[0053] For example, in some embodiments, the antibody specific for claudin 6 and CD3 is a tandem scFv selected from the amino acid sequence of SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 109, SEQ ID NO: 110, or 115, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0054] In some embodiments, the claudin 6 and CD3-specific antibody is an scFv-Fab Fc antibody comprising a first heavy chain sequence, a second heavy chain sequence, and a light chain sequence. For example, the claudin 6 and CD3-specific antibody is selected from a first heavy chain having the amino acid sequence of SEQ ID NO:79, SEQ ID NO:114, or SEQ ID NO:88, a second heavy chain having the amino acid sequence of SEQ ID NO:80, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:111, or SEQ ID NO:116, and a light chain having the amino acid sequence of SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66. In some embodiments, the first heavy chain comprises the amino acid sequence of SEQ ID NO:79, SEQ ID NO:114, or SEQ ID NO:88, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the second heavy chain comprises the amino acid sequence of SEQ ID NO: 80, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 111, or SEQ ID NO: 116, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the light chain comprises the amino acid sequence of SEQ ID NO: 67, SEQ ID NO: 65, or SEQ ID NO: 66, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0055] In some embodiments, the antibody specific for claudin 6 and CD3 is an IgG-(scFV)2 antibody comprising a heavy chain selected from the amino acid sequence of SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 112, or SEQ ID NO: 113, and a light chain selected from the amino acid sequence of SEQ ID NO: 67, SEQ ID NO: 65, or SEQ ID NO: 66. In some embodiments, the heavy chain comprises the amino acid sequence of SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 112, or SEQ ID NO: 113, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the light chain comprises the amino acid sequence of SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0056] In some embodiments, the antibody specific for claudin 6 and CD3 is an scFv-Fab Fc antibody comprising a first heavy chain selected from the amino acid sequence of SEQ ID NO: 79, SEQ ID NO: 114, or SEQ ID NO: 88, a second heavy chain selected from the amino acid sequence of SEQ ID NO: 81, and a light chain selected from the amino acid sequence of SEQ ID NO: 67, SEQ ID NO: 65, or SEQ ID NO: 66. In some embodiments, the antibody comprises the first heavy chain amino acid sequence of SEQ ID NO: 79, SEQ ID NO: 114, or SEQ ID NO: 88, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises the second heavy chain amino acid sequence of SEQ ID NO: 81, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises the light chain amino acid sequence of SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0057] In some embodiments, the antibody specific for claudin 6 and CD3 is an scFv-Fab Fc antibody comprising a first heavy chain selected from the amino acid sequence of SEQ ID NO: 79, SEQ ID NO: 114, or SEQ ID NO: 88, a second heavy chain selected from the amino acid sequence of SEQ ID NO: 117, SEQ ID NO: 119, SEQ ID NO: 118, or SEQ ID NO: 120, and a light chain selected from the amino acid sequence of SEQ ID NO: 67, SEQ ID NO: 65, or SEQ ID NO: 66. In some embodiments, the antibody comprises the first heavy chain amino acid sequence of SEQ ID NO: 79, SEQ ID NO: 114, or SEQ ID NO: 88, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises a second heavy chain amino acid sequence of SEQ ID NO: 117, SEQ ID NO: 119, SEQ ID NO: 118, or SEQ ID NO: 120, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises a light chain amino acid sequence of SEQ ID NO: 67, SEQ ID NO: 65, or SEQ ID NO: 66, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0058] In some embodiments, the antibody specific for claudin 6 and CD3 is an scFv-Fab Fc antibody comprising a first heavy chain selected from the amino acid sequence of SEQ ID NO: 79, SEQ ID NO: 114, or SEQ ID NO: 88, a second heavy chain selected from the amino acid sequence of SEQ ID NO: 121, SEQ ID NO: 123, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, a first light chain selected from the amino acid sequence of SEQ ID NO: 67, SEQ ID NO: 65, or SEQ ID NO: 66, and a second light chain selected from the amino acid sequence of SEQ ID NO: 122, SEQ ID NO: 124, SEQ ID NO: 126, SEQ ID NO: 128, or SEQ ID NO: 130. In some embodiments, the antibody comprises a first heavy chain selected from the amino acid sequence of SEQ ID NO: 79, SEQ ID NO: 114, or SEQ ID NO: 88, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises a second heavy chain selected from the amino acid sequence of SEQ ID NO: 121, SEQ ID NO: 123, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises a first light chain selected from the amino acid sequence of SEQ ID NO: 67, SEQ ID NO: 65, or SEQ ID NO: 66, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises a second light chain selected from the amino acid sequence of SEQ ID NO: 122, SEQ ID NO: 124, SEQ ID NO: 126, SEQ ID NO: 128, or SEQ ID NO: 130, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0059] In various embodiments, an antibody (e.g., a tandem scFv antibody, a scFv-Fab Fc antibody, an IgG-(scFV)2 antibody, and a scFv-Fab Fc antibody), or a fragment or variant thereof, can comprise an amino acid sequence having one or more amino acid mutations (e.g., substitutions or deletions) compared to any of the sequences disclosed herein. In some embodiments, the one or more amino acid mutations can be independently selected from substitutions, insertions, deletions, and truncations. In various embodiments, an antibody (e.g., a tandem scFv antibody, a scFv-Fab Fc antibody, an IgG-(scFV)2 antibody, and a scFv-Fab Fc antibody), or a fragment or variant thereof, comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more amino acid mutations relative to any one of the amino acid sequences disclosed herein.

[0060] In various embodiments, the antibody or antibody format (e.g., tandem scFv antibodies, scFv-Fab Fc antibodies, IgG-(scFV)2 antibodies, and scFv-Fab Fc antibodies), or fragments thereof, or variants thereof, may comprise an amino acid sequence having at least about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to the amino acid sequences disclosed herein.

[0061] In various embodiments, disclosed herein are variants or fragments comprising any of the sequences set forth herein, for example, variants or fragments that are at least about 60%, or at least about 61%, or at least about 62%, or at least about 63%, or at least about 64%, or at least about 65%, or at least about 66%, or at least about 67%, or at least about 68%, or at least about 69%, or at least about 70%, or at least about 71%, or at least about 72%, or at least about 73%, or at least about 74%, or at least about 75%, or at least about 76%, or at least about 77%, or at least about 78%, or at least about 79%, or at least about 80%, or at least about 81%, or at least about 82%, or at least about 83%, or at least about 84%, or at least about 85%, or at least about 86%, or at least about 87%, or at least about 88%, or at least about 89%, or at least about 90%, or at least about 91%, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99%, or at least about 100%, or at least about 101%, or at least about 102%, or at least about 103%, or at least about 104%, or at least about 105%, or at least about 106%, or at least about 107%, or at least about 108%, or at least about 109%, or at least about 110%, or at least about 111%, or at least about 112%, or at least about 113%, or at least about 114%, or at least about 115%, or at least about 116%, or at least about 117 A sequence having about 77%, or at least about 78%, or at least about 79%, or at least about 80%, or at least about 81%, or at least about 82%, or at least about 83%, or at least about 84%, or at least about 85%, or at least about 86%, or at least about 87%, or at least about 88%, or at least about 89%, or at least about 90%, or at least about 91%, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99% sequence identity.

[0062] In some embodiments, the variant is one with conservative amino acid substitutions made at one or more predicted non-essential amino acid residues. For example, a "conservative amino acid substitution" is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain.

[0063] In various embodiments, the amino acid mutation is an amino acid substitution, which may include a conservative substitution and / or a non-conservative substitution. Throughout this disclosure, the terms "mutation" and "substitution" may be used interchangeably as long as the context allows. For example, a substitution of threonine to serine at position 366 of a protein may be referred to as a T366S substitution or a T366S mutation. Those skilled in the art would readily understand that "T366S" means a substitution of threonine to serine at position 366, and therefore, those skilled in the art would readily understand that "T366S mutation" means a substitution.

[0064] "Conservative substitutions" can be made, for example, on the basis of similarity in polarity, charge, size, solubility, hydrophobicity, hydrophilicity, and / or the amphipathic nature of the amino acid residues involved. The 20 naturally occurring amino acids can be divided into six standard amino acid groups: (1) hydrophobic: Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic: Cys, Ser, Thr; Asn, Gln; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that affect chain orientation: Gly, Pro; and (6) aromatic: Trp, Tyr, Phe.

[0065] As used herein, a "conservative substitution" is defined as the replacement of an amino acid with another amino acid listed in the same group of the six standard amino acid groups. For example, the replacement of Asp with Glu retains one negative charge in the modified polypeptide. Furthermore, glycine and proline may be substituted for each other based on their ability to disrupt α-helices.

[0066] As used herein, a "non-conservative substitution" is defined as the replacement of an amino acid with another amino acid listed in a different group of the six standard amino acid groups shown above in (1) to (6).

[0067] For purposes of this disclosure, the term "antibody" is used broadly to include immunoglobulin or antibody molecules, including polyclonal antibodies, monoclonal antibodies (including murine, human, humanized, and chimeric monoclonal antibodies), and antibody fragments (e.g., ScFv) (PLOS Biology | DOI: 10.1371 / journal.pbio.1002344 January 6, 2016, incorporated herein by reference in its entirety).

[0068] Generally, antibodies are proteins or polypeptides that exhibit binding specificity to a specific antigen. Intact antibodies are heterotetrameric glycoproteins composed of two identical light chains and two identical heavy chains. Typically, each light chain is linked to a heavy chain by one covalent disulfide bond, while the number of disulfide bonds varies among heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has a variable domain (VH) at one end followed by multiple constant domains. Each light chain has a variable domain (VL) at one end and a constant domain at the other end, with the light chain constant domain aligned with the first constant domain of the heavy chain and the light chain variable domain aligned with the variable domain of the heavy chain. Antibody light chains of any vertebrate species can be assigned to one of two clearly distinct types, kappa and lambda, based on the amino acid sequence of their constant domains. Immunoglobulins can be assigned to five major classes, IgA, IgD, IgE, IgG, and IgM, depending on the heavy chain constant domain amino acid sequence. IgA and IgG are further subclassified into isotypes IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4.

[0069] As used herein, the term "antibody fragment" refers to an intact antibody, generally the antigen-binding or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments, diabodies, single-chain antibody molecules, and multispecific antibodies formed from at least two intact antibodies or fragments thereof.

[0070] In the present disclosure, the term "antigen" refers to any molecule capable of directly or indirectly generating antibodies.

[0071] As disclosed herein, the terms "specific binding" or "immunospecific binding" or "immunospecifically binds" refer to an antibody binding to a predetermined antigen (e.g., claudin 6) or epitope present on an antigen. In some embodiments, the antibody binds to an epitope present on an antigen at a concentration of about 10 -10 M or less, about 10 -9 M or less, about 10 -8 M or less, about 10 -7 M or less, about 10 -6 M or less, about 10 -5 The antibody binds to a predetermined antigen with a dissociation constant (KD) of M or less, and binds to the predetermined antigen with a KD that is at least two-fold smaller than the KD for binding to a nonspecific antigen other than the predetermined antigen (e.g., BSA, casein, or another nonspecific polypeptide). The terms "antibody recognizing claudin 6" and "antibody specific for claudin 6" are used interchangeably herein with the term "antibody that immunospecifically binds to claudin 6." In the present disclosure, reference may be made to claudin 6. In some embodiments, the antibody is specific for claudin 6 and does not specifically bind to claudin 3, claudin 4, and / or claudin 9.

[0072] "CDR" refers to the complementarity-determining region amino acid sequences of an antibody, which are the hypervariable regions of immunoglobulin heavy and light chains. See, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 4th ed., USDapartment of Health and Human Services, National Institutes of Health (1987). The variable portion of an immunoglobulin has three heavy chain CDRs or CDR regions and three light chain CDRs or CDR regions. Thus, as used herein, "CDR" refers to all three heavy chain CDRs, or all three light chain CDRs, or both all heavy chain CDRs and all light chain CDRs, as appropriate.

[0073] Each variable region contains three hypervariable regions, also known as complementarity-determining regions (CDRs), flanked by four relatively conserved framework regions (FRs). The three CDRs, designated CDR1, CDR2, and CDR3, contribute to antibody binding specificity by providing the majority of contact residues through which the antibody binds to the antigen or epitope. The CDRs of interest are derived from the variable heavy and variable light chain sequences of a donor antibody and can include analogs of natural CDRs, which also share or retain the same antigen-binding specificity and / or neutralization ability as the donor antibody from which they were derived. In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody is a humanized antibody.

[0074] CDRs are based on sequence variability (Wu and Kabat, J. Exp. Med. 132:211-250, 1970). There are six CDRs: three in the variable heavy chain, or VH, typically designated H-CDR1, H-CDR2, and H-CDR3; and three in the variable light chain, or VL, typically designated L-CDR1, L-CDR2, and L-CDR3 (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991). "Hypervariable region," "HVR," or "HV" refers to the region of an antibody variable domain that is variable in structure as defined by Chothia and Lesk (Chothia and Lesk, Mol. Biol. 196:901-917, 1987). There are six HVRs, three in the VH (H1, H2, H3) and three in the VL (L1, L2, L3). Chothia and Lesk refer to structurally conserved HVs as "canonical structures." Another method for describing the regions that form the antigen-binding site was proposed by Lefranc (Lefranc et al., Developmental & Comparative Immunology 27:55-77, 2003), which is based on a comparison of V domains from immunoglobulins and T cell receptors (Lefranc et al., Developmental & Comparative Immunology 27:55-77, 2003). The antigen-binding site can also be defined based on "specificity-determining residue usage (SDRU)" according to Almagro (Almagro, Mol. Recognit. 17:132-43, 2004), where SDRU refers to the amino acid residues of an immunoglobulin that are directly involved in antigen contact.

[0075] As used herein, an "isolated antibody" refers to an antibody that is substantially free of other antibodies having different antigen specificities (e.g., an isolated antibody that specifically binds to claudin 6 is substantially free of antibodies that specifically bind to antigens other than claudin 6). Furthermore, an isolated antibody may be substantially free of other cellular material and / or chemicals. An isolated antibody may also be sterile or pyrogen-free, or formulated as an injectable pharmaceutical product as described herein.

[0076] In some embodiments, sources of DNA encoding non-human antibodies include cell lines that produce antibodies (eg, hybrid cell lines commonly known as hybridomas).

[0077] Claudin 6 / CD3 binder In some embodiments, the antibody specific for claudin 6 and CD3 (e.g., a tandem scFv antibody, an scFv-Fab Fc antibody, an IgG-(scFV)2 antibody, and an scFv-Fab Fc antibody), or a fragment thereof, or a variant thereof, is selected from one of the following amino acid sequences: Bold font refers to the CDRs based on Kabat nomenclature, and underlined formatting refers to the linker.

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[0133] In some embodiments, the antibody specific for claudin 6 and CD3 (e.g., a tandem scFv antibody, an scFv-Fab Fc antibody, an IgG-(scFV)2 antibody, and an scFv-Fab Fc antibody), or a fragment thereof, or a variant thereof, is selected from one of the following amino acid sequences:

[0134] >CH-HAMF5-1HEP-VH (SEQ ID NO: 69) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVAGISSSGRYTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSVGSGVSWSGYVATSLDAWGQGTLVTVSS (SEQ ID NO: 69) >CH-HAMF5-1HEP-VL (SEQ ID NO: 68) SYELTQPPSVSVSPGQTARITCSAGSGLYGWYQQKPGQAPVLVIYGTNKRPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCGSADSSTNAGIFGGGTKLTVL (SEQ ID NO: 68) >CD3 engager (SEQ ID NO: 75) EVQLVESGGGPVQAGGSLRLSCAASGRTYRGYSMGWFRQAPGKEREFVAAIVWSGGNTYYEDSVKGRFTISRDNAKNTMYLQMTSLKPEDSATYYCAAKIRPYIFKIAGQYDYWGQGTQVTVSS (SEQ ID NO: 75) In some embodiments, the antibody specific for claudin 6 and CD3 (e.g., a tandem scFv antibody, an scFv-Fab Fc antibody, an IgG-(scFV)2 antibody, and an scFv-Fab Fc antibody), or a fragment thereof, or a variant thereof, is selected from one of the following amino acid sequences:

[0135] >CH-HAMF5-1HEP-HC (SEQ ID NO: 76) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVAGISSSGRYTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSVGSGVSWSGYVATSLDA WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK THTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 76) >CH-HAMF5-1HEP-LC (SEQ ID NO: 77) SYELTQPPSVSVSPGQTARITCSAGSGLYGWYQQKPGQAPVLVIYGTNKRPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCGSADSSTNAGIFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 77) >3983-HC (SEQ ID NO: 78) EVQLVESGGGPVQAGGSLRLSCAASGRTYRGYSMGWFRQAPGKEREFVAAIVWSGGNTYYEDSVKGRFTISRDNAKNTMYLQMTSLKPEDSATYYCAAKIRPYIFKIAGQYDYWGQGTQVTVSSASPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 78) In some embodiments, the antibodies or antibody fragments or variants disclosed herein (e.g., tandem scFv antibodies, scFv-Fab Fc antibodies, IgG-(scFV)2 antibodies, and scFv-Fab Fc antibodies) comprise a CD3 engager. In some embodiments, the CD3 engager may be selected from muOKT3, huOKT3, huSP34, huUCHT1, and a CD3 nanobody (VHH).

[0136] In some embodiments, antibodies or antibody fragments or variants disclosed herein (e.g., tandem scFv antibodies, scFv-Fab Fc antibodies, IgG-(scFV)2 antibodies, and scFv-Fab Fc antibodies) comprise a linker having one or more glycines and serines replaced with functionally equivalent variations thereof. In some embodiments, the linker is identified in underlined text above. For example, in some embodiments, the linker is selected from the amino acid sequences of GGGGSGGGSGGGGGS (SEQ ID NO: 50), GGGGS (SEQ ID NO: 51), GGSGGSGGSGGSGGVD (SEQ ID NO: 52), and GKPGSGKPGSGKPGSGKPGS (SEQ ID NO: 53).

[0137] In some embodiments, linkers can be derived from natural multidomain proteins or are empirical linkers, such as those described in Chichili et al., (2013), Protein Sci. 22(2):153-167 and Chen et al., (2013), Adv Drug Deliv Rev. 65(10):1357-1369, the entire contents of which are incorporated herein by reference. In some embodiments, linkers can be designed using linker design databases and computer programs, such as those described in Chen et al., (2013), Adv Drug Deliv Rev. 65(10):1357-1369 and Crasto et al., (2000), Protein Eng. 13(5):309-312, the entire contents of which are incorporated herein by reference.

[0138] In some embodiments, the linker is a polypeptide. In some embodiments, the linker is less than about 100 amino acids in length. For example, the linker can be less than about 100, about 95, about 90, about 85, about 80, about 75, about 70, about 65, about 60, about 55, about 50, about 45, about 40, about 35, about 30, about 25, about 20, about 19, about 18, about 17, about 16, about 15, about 14, about 13, about 12, about 11, about 10, about 9, about 8, about 7, about 6, about 5, about 4, about 3, or about 2 amino acids in length. In some embodiments, the linker is flexible. In other embodiments, the linker is rigid. In various embodiments, the linker is composed substantially of glycine and serine residues (e.g., about 30%, or about 40%, or about 50%, or about 60%, or about 70%, or about 80%, or about 90%, or about 95%, or about 97% glycine and serine).

[0139] Additional exemplary linkers include, but are not limited to, the sequences LE, GGGGS (SEQ ID NO: 51), (GGGGS) n (n = 1 to 4) (SEQ ID NO: 54), (Gly) (SEQ ID NO: 55), (Gly) (SEQ ID NO: 56), (EAAAK) n(n = 1 to 3) (SEQ ID NO: 57), A(EAAAK) n A (n = 2 to 5) (SEQ ID NO: 58), AEAAAKEAAAKA (SEQ ID NO: 59), A(EAAAK)4ALEA(EAAAK)4A (SEQ ID NO: 60), PAPAP (SEQ ID NO: 61), KESGSVSSEQLAQFRSLD (SEQ ID NO: 62), EGKSSGSGSESKST (SEQ ID NO: 63), GSAGSAAGSGEF (SEQ ID NO: 64), and (XP) n (n=1 to 5) (SEQ ID NO: 131) (wherein X represents any amino acid (for example, Ala, Lys, or Glu)).

[0140] In various embodiments, the linker can be functional. For example, but not limited to, the linker can function to improve folding and / or stability, improve expression, improve pharmacokinetics, and / or improve biological activity of the composition. In another example, the linker can function to target the composition to a particular cell type or location.

[0141] In some embodiments, disclosed herein is a composition comprising a tandem single chain variable fragment (scFv) specific for claudin-6 and CD3, wherein the scFv comprises: I. (a) the amino acid sequence of SEQ ID NO: 82, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SAGSGLYG (SEQ ID NO: 1) or a variant thereof, the LCDR2 sequence comprises the amino acid sequence of GTNKRPS (SEQ ID NO: 2) or a variant thereof, and the LCDR3 sequence comprises the amino acid sequence of GSADSSTNAGI (SEQ ID NO: 3) or a variant thereof; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SYAMN (SEQ ID NO: 4) or a variant thereof, HCDR2 comprises the amino acid sequence of GISSSGRYTGYADSVKG (SEQ ID NO: 5) or a variant thereof, and HCDR3 comprises the amino acid sequence of SVGSGVSWSGYVATSLDA (SEQ ID NO: 6) or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of RYTMH (SEQ ID NO: 7) or a variant thereof, HCDR2 comprises the amino acid sequence of YINPSRGYTNYNQKFKD (SEQ ID NO: 8) or a variant thereof, and HCDR3 comprises the amino acid sequence of YYDDHYCLDY (SEQ ID NO: 9) or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of RASSSVSYMN (SEQ ID NO: 10) or a variant thereof, LCDR2 comprises the amino acid sequence of DTSKVAS (SEQ ID NO: 11) or a variant thereof, and LCDR3 comprises the amino acid sequence of QQWSSNPLT (SEQ ID NO: 12) or a variant thereof; II. (a) the amino acid sequence of SEQ ID NO: 83, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SGGSGSYG (SEQ ID NO: 13) or a variant thereof, LCDR2 comprises the amino acid sequence of GTYKRPS (SEQ ID NO: 14) or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SVGSGVSWSGYVATSLDV (SEQ ID NO: 15) or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 8 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 10 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 11 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 12 or a variant thereof; III. (a) the amino acid sequence of SEQ ID NO: 84, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 sequence comprises SEQ ID NO: 5 or a variant thereof, and the HCDR3 sequence comprises SEQ ID NO: 6 or a variant thereof; and (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of GYSMG (SEQ ID NO: 16) or a variant thereof, HCDR2 comprises the amino acid sequence of AIVWSGGNTYYEDSVKG (SEQ ID NO: 17) or a variant thereof, and HCDR3 comprises the amino acid sequence of KIRPYIFKIAGQYDY (SEQ ID NO: 18) or a variant thereof; IV. (a) the amino acid sequence of SEQ ID NO: 85, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; and (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; V. (a) the amino acid sequence of SEQ ID NO: 93, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of KYAMN (SEQ ID NO: 19) or a variant thereof, HCDR2 comprises the amino acid sequence of RIRSKYNNYATYYADSVKD (SEQ ID NO: 20) or a variant thereof, and HCDR3 comprises the amino acid sequence of HGNFGNSYISYWAY (SEQ ID NO: 21) or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of GSSTGAVTSGNYPN (SEQ ID NO: 22) or a variant thereof, LCDR2 comprises the amino acid sequence of GTKFLAP (SEQ ID NO: 23) or a variant thereof, and LCDR3 comprises the amino acid sequence of VLWYSNRWV (SEQ ID NO: 24) or a variant thereof; VI. (a) the amino acid sequence of SEQ ID NO: 94, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; VII. (a) the amino acid sequence of SEQ ID NO: 95, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of TYAMN (SEQ ID NO: 25) or a variant thereof, HCDR2 comprises the amino acid sequence of RIRSKYNNYATYYADSVKG (SEQ ID NO: 26) or a variant thereof, and HCDR3 comprises the amino acid sequence of HGNFGDSYVSWFAY (SEQ ID NO: 27) or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of GSSTGAVTTSNYAN (SEQ ID NO: 28) or a variant thereof, LCDR2 comprises the amino acid sequence of GTNKRAP (SEQ ID NO: 29) or a variant thereof, and LCDR3 comprises the amino acid sequence of ALWYSNHWV (SEQ ID NO: 30) or a variant thereof; VIII. (a) the amino acid sequence of SEQ ID NO: 96, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; IX. (a) the amino acid sequence of SEQ ID NO: 97, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, HCDR2 comprises the amino acid sequence of RIRSKYNNYATYYADSVKS (SEQ ID NO: 31) or a variant thereof, and HCDR3 comprises the amino acid sequence of HGNFGNSYVSWFAY (SEQ ID NO: 32) or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of RSSTGAVTTSNYAN (SEQ ID NO: 33) or a variant thereof, LCDR2 comprises the amino acid sequence of GANKRAP (SEQ ID NO: 34) or a variant thereof, and LCDR3 comprises the amino acid sequence of ALWYSNLWV (SEQ ID NO: 35) or a variant thereof; X. (a) the amino acid sequence of SEQ ID NO: 98, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; XI. (a) the amino acid sequence of SEQ ID NO: 99, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, HCDR2 comprises the amino acid sequence of YINPSRGYTNYNQKVKD (SEQ ID NO: 36) or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SASSSVSYMN (SEQ ID NO: 37) or a variant thereof, LCDR2 comprises the amino acid sequence of DTSKLAS (SEQ ID NO: 38) or a variant thereof, and LCDR3 comprises the amino acid sequence of QQWSSNPFT (SEQ ID NO: 39) or a variant thereof; XII. (a) the amino acid sequence of SEQ ID NO: 100, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; XIII. (a) the amino acid sequence of SEQ ID NO: 109, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of GYTMN (SEQ ID NO: 40) or a variant thereof, HCDR2 comprises the amino acid sequence of LINPYKGVSTYNQKVKG (SEQ ID NO: 41) or a variant thereof, and HCDR3 comprises the amino acid sequence of SGYYGDSDWYFDV (SEQ ID NO: 42) or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of RASQDIRNYLN (SEQ ID NO: 43) or a variant thereof, LCDR2 comprises the amino acid sequence of YTSRLHS (SEQ ID NO: 44) or a variant thereof, and LCDR3 comprises the amino acid sequence of QQGNTLPWT (SEQ ID NO: 45) or a variant thereof; and XIV. (a) the amino acid sequence of SEQ ID NO: 110, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, HCDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and HCDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein LCDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, LCDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; In any of the above sequences, optionally, one or more of the glycine and serine-containing linkers are replaced with another peptide linker or a functionally equivalent variation thereof.

[0142] In some embodiments, the antibody (eg, a tandem scFv antibody specific for claudin-6 and CD3) comprises the CDR sequences shown in Table 1 below.

[0143] [Table 1-1]

[0144] [Table 1-2]

[0145] [Table 1-3]

[0146] [Table 1-4]

[0147] [Table 1-5]

[0148] In some embodiments, disclosed herein is a composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, wherein the antibody is (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SMGSGVSWSGYVATSIDV (SEQ ID NO: 47) or a variant thereof; (b) a second heavy chain selected from: (i.) SEQ ID NO: 80; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or (ii.) SEQ ID NO: 89; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; or (iii.) SEQ ID NO: 90; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of RSSTGAVTTSNYA (SEQ ID NO: 48) or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; or (iv.) SEQ ID NO: 91, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of GSSTGAVTSGNYP (SEQ ID NO: 49) or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; or (v.) SEQ ID NO: 92, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; or (vi.) SEQ ID NO: 111, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; and (c) a first light chain selected from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; In any of the above sequences, optionally, one or more of the glycine and serine-containing linkers are replaced with another peptide linker or a functionally equivalent variation thereof.

[0149] In some embodiments, the Fc is derived from an IgG.

[0150] In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0151] In some embodiments, antibodies are formed through knobs-in-hole interactions in the Fc region. In some embodiments, the human IgG Fc comprises one or more mutations to promote knobs-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V is selected from.

[0152] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate effector function of the Fc domain, hi some embodiments, the mutations are L234A and L235A (LALA) substitutions in human IgG1.

[0153] In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0154] In some embodiments, the scFv-Fab antibody specific for claudin-6 and CD3 comprises the CDR sequences shown in Table 2 below.

[0155] [Table 2-1]

[0156] [Table 2-2]

[0157] [Table 2-3]

[0158] In some embodiments, the scFv-Fab antibody specific for claudin-6 and CD3 comprises the CDR sequences shown in Table 3 below.

[0159] [Table 3-1]

[0160] [Table 3-2]

[0161] [Table 3-3]

[0162] In some embodiments, the scFv-Fab antibody specific for claudin-6 and CD3 comprises the CDR sequences shown in Table 4 below.

[0163] [Table 4-1]

[0164] [Table 4-2]

[0165] In some embodiments, disclosed herein is a composition comprising an IgG-(scFV)2 antibody specific for claudin-6 and CD3, wherein the antibody is (a) a heavy chain chosen from: (i.) SEQ ID NO: 86; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (ii.) SEQ ID NO: 87; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (iii.) SEQ ID NO: 101; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; (iv.) SEQ ID NO: 102, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; (v.) SEQ ID NO: 103, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; (vi.) SEQ ID NO: 104, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; (vii.) SEQ ID NO: 105; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; (viii.) SEQ ID NO: 106, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; (ix.) SEQ ID NO: 107, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; (x.) SEQ ID NO: 108, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; (xi.) SEQ ID NO: 112, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; (xii.) SEQ ID NO: 113, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; and (b) a light chain chosen from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; In any of the above sequences, optionally, one or more of the glycine and serine-containing linkers are replaced with another peptide linker or a functionally equivalent variation thereof.

[0166] In some embodiments, the Fc is derived from an IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0167] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate effector function of the Fc domain, hi some embodiments, the mutations are L234A and L235A (LALA) substitutions in human IgG1.

[0168] In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0169] In some embodiments, the IgG-(scFv)2 antibody specific for claudin-6 and CD3 comprises the CDR sequences shown in Table 5 below.

[0170] [Table 5-1]

[0171] [Table 5-2]

[0172] [Table 5-3]

[0173] [Table 5-4]

[0174] [Table 5-5]

[0175] [Table 5-6]

[0176] In some embodiments, disclosed herein is a composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, wherein the antibody is (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: SEQ ID NO: 81, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; and (c) a light chain chosen from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66 an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; In any of the above sequences, optionally, one or more of the glycine and serine-containing linkers are replaced with another peptide linker or a functionally equivalent variation thereof.

[0177] In some embodiments, the Fc is derived from an IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0178] In some embodiments, antibodies are formed through knobs-in-hole interactions in the Fc region. In some embodiments, the human IgG Fc comprises one or more mutations to promote knobs-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V is.

[0179] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate effector function of the Fc domain. In some embodiments, the mutations are L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0180] In some embodiments, disclosed herein is a composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, wherein the antibody is (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i.) SEQ ID NO: 117, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (ii.) SEQ ID NO: 119; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (iii.) SEQ ID NO: 118; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iv.) SEQ ID NO: 120; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; and (c) a light chain chosen from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66 an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; In any of the above sequences, optionally, one or more of the glycine and serine-containing linkers are replaced with another peptide linker or a functionally equivalent variation thereof.

[0181] For example, the linker of GGGGSGGGSGGGGGS (SEQ ID NO:50) exemplified in various embodiments herein (above and below) may be replaced with a linker of LE, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, or SEQ ID NO:131.

[0182] In some embodiments, the Fc is derived from an IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0183] In some embodiments, antibodies are formed through knobs-in-hole interactions in the Fc region. In some embodiments, the human IgG Fc comprises one or more mutations to promote knobs-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V is.

[0184] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate effector function of the Fc domain. In some embodiments, the mutations are L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0185] In some embodiments, disclosed herein is a composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, wherein the antibody is (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i) SEQ ID NO: 121; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; (ii) SEQ ID NO: 123; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; (iii) SEQ ID NO: 125; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; (iv) SEQ ID NO: 127, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; (v) SEQ ID NO: 129, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; and (c) a first light chain selected from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; and (d) a second light chain selected from: (i) SEQ ID NO: 122; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; or (ii) SEQ ID NO: 124; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; or (iii) SEQ ID NO: 126; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; or (iv) SEQ ID NO: 128, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; or (v) SEQ ID NO: 130, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; In any of the above sequences, optionally, one or more of the glycine and serine-containing linkers are replaced with another peptide linker or a functionally equivalent variation thereof.

[0186] In some embodiments, disclosed herein are bispecific antibodies comprising three polypeptides (e.g., a first polypeptide, a second polypeptide, and a third polypeptide) that form a first antigen-binding domain that binds to CLDN6 and a second antigen-binding domain that binds to CD3. In some embodiments, the first polypeptide comprises a first variable light chain region (first V L ), wherein the first variable light chain region comprises a CDR1 sequence comprising the amino acid sequence of SEQ ID NO: 1, a CDR2 sequence comprising the amino acid sequence of SEQ ID NO: 2, and a CDR3 sequence comprising the amino acid sequence of SEQ ID NO: 3. In some embodiments, the second polypeptide comprises a first light chain comprising a first variable light chain region (first V HIn some embodiments, the third polypeptide comprises a first heavy chain and a second light chain, wherein the second heavy chain comprises a second variable heavy chain region (second V) comprising a CDR1 sequence comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 sequence comprising the amino acid sequence of SEQ ID NO: 5, and a CDR3 sequence comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the third polypeptide comprises a second heavy chain and a second light chain, wherein the second heavy chain comprises a second variable heavy chain region (second V) comprising a CDR1 sequence comprising the amino acid sequence of SEQ ID NO: 25, a CDR2 sequence comprising the amino acid sequence of SEQ ID NO: 26, and a CDR3 sequence comprising the amino acid sequence of SEQ ID NO: 27. H ), and the second light chain comprises a second variable light chain region (second V) comprising a CDR1 sequence comprising the amino acid sequence of SEQ ID NO: 28, a CDR2 sequence comprising the amino acid sequence of SEQ ID NO: 29, and a CDR3 sequence comprising the amino acid sequence of SEQ ID NO: 30. L In some embodiments, the second heavy chain and the second light chain are connected by a peptide linker. In some embodiments, the peptide linker is as described herein. In some embodiments, the peptide linker comprises the amino acid sequence of SEQ ID NO: 53. In some embodiments, the peptide linker comprising one or more glycines and serines is replaced with another peptide linker or a functionally equivalent variation thereof. In some embodiments, the first V L and the first V H interact to form an antigen-binding domain that binds to CLDN6. In some embodiments, the second V L and the second V H interact to form an antigen-binding domain that binds to CD3. In some embodiments, the second V L and the second V H is in scFv format. In some embodiments, the first V L and the first V H is in the Fab format or a fragment thereof.

[0187] In some embodiments, the first variable light chain region of the first polypeptide comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0188] In some embodiments, the first variable heavy chain region of the second polypeptide comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0189] In some embodiments, the second variable heavy chain region of the third polypeptide has the amino acid sequence: EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVGRIRSKYNNYATYYADSVKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGDSYVSWFAYWGQGTLVTVSS (SEQ ID NO: 70), or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0190] In some embodiments, the second variable light chain region of the third polypeptide has the amino acid sequence: QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQQKPGKSPRGLIGGTNKRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNHWVFGGGTKLTVL (SEQ ID NO: 71), or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0191] In some embodiments, the first polypeptide comprising a light chain comprises a first variable light chain region and a light chain constant domain (sometimes referred to as a first light chain constant domain). In some embodiments, the first light chain constant domain has the following amino acid sequence: GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 72), or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0192] In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0193] In some embodiments, the second polypeptide comprising the first heavy chain comprises a first variable heavy chain region and a heavy chain constant domain (sometimes referred to as a first heavy chain constant domain). In some embodiments, the first heavy chain constant domain has the amino acid sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 73), or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0194] In some embodiments, the second polypeptide comprises the amino acid sequence of SEQ ID NO: 79, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0195] In some embodiments, the third polypeptide comprises a constant domain. In some embodiments, the constant domain is linked to the C-terminus of the second variable light chain region. In some embodiments, there is no peptide linker between the C-terminus of the second variable light chain region and the constant domain. In some embodiments, the constant domain present in the third polypeptide has the following amino acid sequence: ASPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 74), or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0196] In some embodiments, the third polypeptide comprises the amino acid sequence of SEQ ID NO: 89, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0197] In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO:67, the second polypeptide comprises the amino acid sequence of SEQ ID NO:79, and the third polypeptide comprises the amino acid sequence of SEQ ID NO:89.

[0198] As used herein, the term constant domain refers to an Fc domain. The constant domains exemplified above are optional embodiments, and other constant domains may be substituted for the constant domains described herein.

[0199] In some embodiments, the Fc is derived from an IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0200] In some embodiments, antibodies are formed through knobs-in-hole interactions in the Fc region. In some embodiments, the human IgG Fc comprises one or more mutations to promote knobs-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V is.

[0201] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate effector function of the Fc domain. In some embodiments, the mutations are L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0202] In some embodiments, the composition simultaneously binds to claudin-6 and CD3.

[0203] In some embodiments, the composition binds to claudin 6 with an affinity of less than 10 nM and with an affinity that is at least 100-fold greater than that of claudin 9, claudin 3, and / or claudin 4.

[0204] In any of the embodiments disclosed herein, the composition induces cytotoxicity.

[0205] In any of the embodiments disclosed herein, the composition induces T cell cytotoxicity.

[0206] In any of the embodiments disclosed herein, the composition induces T cell dependent cytotoxicity.

[0207] In any of the embodiments disclosed herein, the composition increases the expression and / or release of one or more cytokines. In any of the embodiments disclosed herein, the composition increases the expression and / or release of one or more cytokines selected from IL-2, IL-6, IL-10, IFN-γ, and TNF-α.

[0208] As defined herein, an antibody can be formed by heterodimerization of two Fc domains linked to an antibody variable domain, which can be a VH or can be linked to an scFv format antibody. In some embodiments, the antibody polypeptide comprises a first constant domain and a second constant domain. The constant domain can be based on IgG1, IgG2, IgG3, or IgG4. In some embodiments, the constant domain is a human constant domain. As defined herein, the constant domain is based on a human IgG1 constant domain, as defined herein. These constant domains can be incorporated into any format of antibody as defined herein.

[0209] In some embodiments, the first constant domain comprises a T366W mutation and the second constant domain comprises T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises T366Y and Y407T mutations or T366Y and F405A mutations and the second constant domain comprises T394W and Y407T mutations. In some embodiments, the first constant domain comprises T366W and D399C mutations and the second constant domain comprises T366S, L368A, K392C, and Y407V mutations. In some embodiments, the first constant domain comprises T366W and K392C mutations and the second constant domain comprises T366S, L368A, D399C, and Y407V mutations. In some embodiments, the first constant domain comprises S354C and T366W mutations and the second constant domain comprises Y349C, T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises Y349C and T366W mutations and the second constant domain comprises S354C, T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises E356C and T366W mutations and the second constant domain comprises Y349C, T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises Y349C and T366W mutations and the second constant domain comprises E356C, T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises E357C and T366W mutations and the second constant domain comprises Y349C, T366S, L368A, and Y407V mutations, hi some embodiments, the first constant domain comprises Y349C and T366W mutations and the second constant domain comprises E357C, T366S, L368A, and Y407V mutations.

[0210] In some embodiments, the first and second constant domains each independently comprise a L234A and a L235A (LALA) substitution, where numbering is according to EU numbering for human IgG1. In some embodiments, the first and second constant domains each comprise a L234A and a L235A (LALA) substitution.

[0211] The constant domains (Fc) (e.g., the first and second constant domains) may also include other mutations as defined herein, which may confer increased specificity for an Fc receptor type (e.g., FcgRIIA).

[0212] Pharmaceutical Composition In some embodiments, disclosed herein is a pharmaceutical composition comprising the isolated antibody of any one of the preceding embodiments, or a nucleic acid molecule encoding same. In some embodiments, the composition is an injectable pharmaceutical composition. In some embodiments, the composition is sterile. In some embodiments, the composition is pyrogen-free.

[0213] This document also provides pharmaceutical compositions comprising the compositions described herein in combination with a pharmaceutically acceptable carrier. A "pharmaceutically acceptable carrier" (also referred to as an "excipient" or "carrier") is a pharmaceutically acceptable solvent, suspending agent, stabilizer, or other pharmacologically inert vehicle for delivering one or more therapeutic compounds to a subject (e.g., a mammal, such as a human, non-human primate, dog, cat, sheep, pig, horse, cow, mouse, rat, rabbit, etc.), which is non-toxic to the cells or subject exposed thereto at the dosages and concentrations employed. A pharmaceutically acceptable carrier may be liquid or solid, and may be selected, keeping in mind the proposed mode of administration, to provide the desired bulk, consistency, and other relevant transport and chemical properties when combined with the therapeutic compound(s) and one or more of the other components of a given pharmaceutical composition. Typical pharmaceutically acceptable carriers that do not deleteriously react with amino acids include, by way of example and not limitation, water, saline, binders (e.g., polyvinylpyrrolidone or hydroxypropylmethylcellulose), fillers (e.g., lactose and other sugars, gelatin, or calcium sulfate), lubricants (e.g., starch, polyethylene glycol, or sodium acetate), disintegrants (e.g., starch or sodium starch glycolate), and wetting agents (e.g., sodium lauryl sulfate). Pharmaceutically acceptable carriers also include pH buffered aqueous solutions or liposomes (small vesicles composed of various types of lipids, phospholipids, and / or surfactants, useful for delivery of drugs to mammals).Further examples of pharmaceutically acceptable carriers include buffers (e.g., phosphate, citric acid, and other organic acids), antioxidants (e.g., ascorbic acid), low molecular weight (less than about 10 residues) polypeptides, proteins (e.g., serum albumin, gelatin, or immunoglobulins), hydrophilic polymers (e.g., polyvinylpyrrolidone), amino acids (e.g., glycine, glutamine, asparagine, arginine, or lysine), monosaccharides, disaccharides, and other carbohydrates (including glucose, mannose, or dextrins), chelating agents (e.g., EDTA), sugar alcohols (e.g., mannitol or sorbitol), salt-forming counterions (e.g., sodium), and / or non-ionic surfactants (e.g., TWEEN™, polyethylene glycol (PEG), and PLURONICS™).

[0214] Pharmaceutical compositions can be formulated by mixing one or more active agents with one or more physiologically acceptable carriers, diluents, and / or adjuvants, and optionally other agents commonly incorporated into formulations to improve migration, delivery, tolerability, etc. Pharmaceutical compositions can be formulated, for example, into lyophilized preparations, aqueous solutions, dispersions, or solid preparations such as tablets, dragees, or capsules. Many suitable formulations can be found in the formulary known to all pharmaceutical chemists: Remington's Pharmaceutical Sciences (18th ed., Mack Publishing Company, Easton, PA (1990)), especially Chapter 87 by Block, Lawrence. Such formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic)-containing vesicles (e.g., LIPOFECTIN™), DNA conjugates, anhydrous absorbent pastes, oil-in-water and water-in-oil emulsions, emulsion carbowax (polyethylene glycol of various molecular weights), semi-solid gels, and semi-solid mixtures containing carbowax. Any of the foregoing mixtures may be suitable for the treatments and therapies described herein, so long as the active agent in the formulation is not inactivated by the formulation and the formulation is physiologically compatible and tolerable for the route of administration. See also Baldrick, Regul Toxicol Pharmacol 32:210-218, 2000; Wang, Int J Pharm 203:1-60, 2000; Charman J Pharm Sci 89:967-978, 2000; and Powell et al. PDA J Pharm Sci Technol 52:238-311, 1998), and citations therein, for additional information related to formulations, excipients, and carriers well known to pharmaceutical chemists.

[0215] Pharmaceutical compositions include, but are not limited to, solutions, emulsions, aqueous suspensions, and liposome-containing formulations. These compositions can be produced from a variety of components, including, for example, preformed liquids, self-emulsifying solids, and self-emulsifying semisolids. Emulsions are often biphasic systems consisting of two immiscible liquid phases intimately mixed and dispersed with each other. Generally, emulsions are either water-in-oil (w / o) or oil-in-water (o / w) types. Emulsion formulations are widely used for oral delivery of therapeutic agents due to their ease of formulation and effectiveness in solubilization, absorption, and bioavailability.

[0216] The compositions and formulations may contain sterile aqueous solutions, which may also contain buffers, diluents, and other suitable additives (e.g., penetration enhancers, carrier compounds, and other pharmaceutically acceptable carriers). The compositions may additionally contain other auxiliary components conventionally found in pharmaceutical compositions. Thus, the compositions may also contain compatible pharmaceutically active substances (e.g., antipruritics, astringents, local anesthetics, or anti-inflammatory agents), or additional substances useful in physically formulating various dosage forms of the compositions provided herein (e.g., dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickeners, and stabilizers). Furthermore, the compositions may be mixed with auxiliary substances such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring agents, flavoring agents, and aromatic substances. However, when added, such substances should not unduly interfere with the biological activity of the polypeptide components in the compositions provided herein. The formulations may be sterilized, if necessary.

[0217] In some embodiments, compositions including those provided herein may be in the form of a solution or powder, with or without a diluent to create an injectable suspension. The compositions may also contain additional components, including, but not limited to, a pharmaceutically acceptable vehicle (e.g., saline, water, lactic acid, mannitol, or a combination thereof).

[0218] Any suitable method can be used to administer the compositions described herein to a mammal. Administration can be, for example, parenteral (e.g., by subcutaneous, intrathecal, intracerebroventricular, intramuscular, or intraperitoneal injection, or by intravenous infusion). Administration can be rapid (e.g., by injection) or over a period of time (e.g., by slow infusion or administration of a sustained-release formulation). In some embodiments, administration can be topical (e.g., transdermal, sublingual, intraocular, or intranasal), pulmonary (e.g., by inhalation or insufflation of a powder or aerosol), or oral. Furthermore, compositions, including compositions described herein, can be administered before, after, or instead of surgical removal of a tumor.

[0219] The antibodies, compositions, or pharmaceutical compositions defined herein can be administered at any suitable interval to achieve the desired effect in a subject. In some embodiments, the antibodies, compositions, or pharmaceutical compositions are administered daily, every other day, weekly, biweekly, once every three weeks, or monthly (i.e., once every four weeks). In some embodiments, the methods defined herein include administering the antibodies, compositions, or pharmaceutical compositions to a cell or a subject in need thereof at intervals of daily, every other day, weekly, every three weeks, or monthly (i.e., once every four weeks).

[0220] In some embodiments, disclosed herein is a nucleic acid molecule encoding an antibody or amino acid sequence according to any of the preceding embodiments.

[0221] In some embodiments, disclosed herein is a vector comprising the nucleic acid molecule of any of the preceding embodiments.

[0222] In some embodiments, disclosed herein is a cell comprising the nucleic acid molecule of any of the preceding embodiments or the vector of any of the preceding embodiments.

[0223] In some embodiments, disclosed herein is a method for modulating and / or targeting claudin 6 and CD3 in a biological cell, comprising contacting the cell with a composition described in any of the preceding embodiments.

[0224] In some embodiments, disclosed herein is a method for modulating the activity of claudin 6 in a biological cell, comprising contacting a cell that expresses claudin 6 with a composition described in any of the preceding embodiments.

[0225] In some embodiments, disclosed herein is a method for inhibiting the function of claudin 6 in a biological cell, the method comprising contacting a cell expressing claudin 6 with a composition described in any of the preceding embodiments.

[0226] Treatment method In some embodiments, disclosed herein is a method for treating or preventing cancer, comprising administering to a subject in need thereof an effective amount of the composition of any of the preceding embodiments.

[0227] In some embodiments, disclosed herein is the use of a composition of any of the preceding embodiments for the preparation of a medicament for treating or preventing cancer.

[0228] In some embodiments, disclosed herein is a method for treating cancer, wherein the cancer is selected from the group consisting of basal cell carcinoma, biliary tract cancer, bladder cancer, bone cancer, brain and central nervous system cancer, breast cancer, peritoneal cancer, cervical cancer, choriocarcinoma, colorectal cancer, connective tissue cancer, digestive system cancer, endometrial cancer, esophageal cancer, eye cancer, head and neck cancer, gastric cancer (including gastrointestinal cancer), glioblastoma, glioma, liver cancer, hepatocellular carcinoma, intraepithelial neoplasia, kidney cancer or renal carcinoma, laryngeal cancer, leukemia, liver cancer, lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma), melanoma, myeloma, neuroblastoma, oral cancer (lip, tongue, mouth, and pharynx), ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, malignant rhabdoid tumor, rectal cancer, respiratory system cancer, salivary gland cancer, sarcoma, skin cancer, squamous cell carcinoma, stomach cancer, testicular cancer, thyroid cancer, uterine or endometrial cancer, urinary system cancer, vulvar cancer, lymphoma (Hodgkin's lymphoma and non-Hodgkin's lymphoma, and B and rheumatoid arthritis (rheumatoid arthritis), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, chronic myeloblastic leukemia, and other carcinomas and sarcomas, and post-transplant lymphoproliferative disorder (PTLD), and abnormal blood vessel proliferation associated with nevus syndrome, edema (e.g., associated with brain tumors), and Meigs syndrome.

[0229] As a non-limiting example, assessment of the occurrence, presence, and / or progression of cancer in a subject can be assessed according to the Tumor / Node / Metastasis (TNM) classification system (International Union Against Cancer, 6th edition, 2002) or the Whitmore-Jewett staging system (American Urological Association). Typically, cancer is staged using a combination of physical examination, blood tests, and medical imaging. If tumor tissue is obtained by biopsy or surgery, examination of the tissue under a microscope can also provide pathological staging. In some embodiments, the stage or grade of cancer determines the prognosis of the cancer and assists physicians in selecting appropriate regulatory therapies.

[0230] In some embodiments, prevention of cancer onset or progression is assessed using overall staging, with non-limiting examples including: stage I cancers localized to one part of the body, typically a small area; stage II cancers progress locally and grow within nearby tissues or lymph nodes, similar to stage III cancers. Whether a cancer is designated as stage II or stage III may depend on the particular type of cancer. The specific criteria for stages II and III may vary depending on the diagnosis. Stage IV cancers often have metastasized or spread to other organs or the entire body. Cancer onset or progression can be assessed using conventional methods available to those skilled in the art, such as physical examinations, blood tests, and imaging scans (e.g., X-rays, MRIs, CT scans, ultrasounds, etc.).

[0231] As disclosed herein, administering or administering a treatment / therapy refers to a treatment / therapy in which the subject receives a beneficial effect (e.g., a reduction, decrease, attenuation, stabilization, amelioration, suppression, inhibition, or arrest of the onset or progression of cancer or its symptoms).

[0232] In some embodiments, the treatment / therapy a subject receives, or the prevention of the onset of cancer, results in at least one or more of the following effects: (1) a reduction or alleviation of the severity of cancer and / or genetic disease or disorder, and / or symptoms associated therewith; (2) a reduction in the duration of symptoms associated with cancer and / or genetic disease or disorder; (3) a prevention of the recurrence of symptoms associated with cancer and / or genetic disease or disorder; (4) a reduction in cancer and / or genetic disease or disorder, and / or symptoms associated therewith; (5) a reduction in the subject's need for hospitalization; (6) a reduction in the length of hospitalization; (7) an increase in the subject's survival; (8) an inhibition of the progression of cancer and / or genetic disease or disorder, and / or symptoms associated therewith; (9) an enhancement or improvement in the therapeutic efficacy of another therapy; (10) a reduction or elimination of cancer cell populations and / or cell populations associated with genetic disease or disorder; (11) a reduction in tumor or neoplasm growth; (12) a reduction in tumor size; (13) reduction in tumor formation; (14) eradication, removal, or control of primary, regional, and / or metastatic cancer; (15) reduction in the number or size of metastases; (16) reduction in mortality; (17) increase in the length of time a subject survives cancer-free; (18) increase in recurrence-free survival; (19) increase in the number of subjects in remission; (20) reduction in hospitalization rates; (21) maintenance of tumor size, no increase in tumor size, or an increase in size of less than about 5% or about 10% after administration of therapy, as measured by conventional methods available to those skilled in the art (e.g., X-ray, MRI, CT scan, ultrasound, etc.); (22) prevention of the occurrence or development of cancer and / or genetic diseases or disorders, and / or symptoms associated therewith; (23) increase in the length of remission in a subject; (24) reduction in the number of symptoms associated with cancer and / or genetic diseases or disorders; (25) increase in symptom-free survival in subjects with cancer and / or subjects associated with genetic diseases or disorders; and / or (26) limitation or reduction of metastases. In some embodiments, the treatment / therapy a subject receives does not cure the cancer but prevents the progression or worsening of the disease. In certain embodiments, the treatment / therapy a subject receives does not prevent the onset / occurrence of cancer but may prevent the onset of cancer symptoms.

[0233] In some embodiments, treated subjects do not develop cytokine release syndrome (CRS) or significant CRS-related clinical symptoms or toxicities, including, but not limited to, fever, chills, fatigue, weakness, loss of appetite, nausea, vomiting, diarrhea, headache, joint or muscle pain, skin rash, low blood pressure, increased heart rate, irregular heartbeat, tachycardia, decreased cardiac function, swelling, fluid accumulation (edema), confusion, dizziness, seizures, hallucinations, poor coordination, speech or swallowing problems, tremors, problems controlling movements, cough, shortness of breath, rapid breathing, decreased lung function, reduced oxygen levels, decreased kidney or liver function, increased blood cytokine levels, electrolyte changes, and changes in blood clotting. In some embodiments, after administration of an antibody as defined herein, there is no increase or no significant increase in blood levels of interleukin-6 (IL-6), interleukin-10 (IL-10), interferon (IFN)-γ, monocyte chemoattractant protein 1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF), IL-1, IL-2, IL-2-receptor-α, or IL-8.

[0234] In some embodiments, "preventing" the onset or progression of cancer in a subject in need thereof refers to inhibiting or blocking the cancer or disorder. In some embodiments, the methods disclosed herein prevent or inhibit cancer or a disorder at any amount or level. In some embodiments, the methods disclosed herein prevent or inhibit cancer or a genetic disease or disorder by at least or about 10% inhibition (e.g., at least or about 20% inhibition, at least or about 30% inhibition, at least or about 40% inhibition, at least or about 50% inhibition, at least or about 60% inhibition, at least or about 70% inhibition, at least or about 80% inhibition, at least or about 90% inhibition, at least or about 95% inhibition, at least or about 98% inhibition, or at least or about 100% inhibition).

[0235] In some embodiments, disclosed herein is an isolated antibody comprising one or more of the sequences disclosed herein.

[0236] As used herein, the word "include" and variations thereof are intended to be non-limiting, and the recitation of items in a list does not exclude other similar items that may also be useful in the materials, compositions, devices, and methods of this technology. Similarly, the terms "can" and "may" and variations thereof are intended to be non-limiting, such that a recitation that an embodiment can or may include certain elements or features does not exclude other embodiments of this technology that do not contain those elements or features. Although the open-ended term "comprising" is used herein as a synonym for terms such as including, containing, or having to describe and claim this disclosure, the technology, or embodiments thereof, may alternatively be described using more restrictive terminology, such as "consisting of" or "consisting essentially of" the listed components.

[0237] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, the preferred methods and materials are described herein. All cited publications, patents, and patent publications are incorporated herein by reference in their entirety for all purposes.

[0238] List of embodiments In some embodiments, the following embodiments are provided:

[0239] 1. A composition comprising a tandem single-chain variable fragment (scFv) specific for claudin 6 and CD3, I. (a) the amino acid sequence of SEQ ID NO: 82, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 8 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 10 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 11 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 12 or a variant thereof; II. (a) the amino acid sequence of SEQ ID NO: 83, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 8 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 10 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 11 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 12 or a variant thereof; III. (a) the amino acid sequence of SEQ ID NO: 84, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; and (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; IV. (a) the amino acid sequence of SEQ ID NO: 85, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; and (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; V. (a) the amino acid sequence of SEQ ID NO: 93, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; VI. (a) the amino acid sequence of SEQ ID NO: 94, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; VII. (a) the amino acid sequence of SEQ ID NO: 95, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; VIII. (a) the amino acid sequence of SEQ ID NO: 96, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; IX. (a) the amino acid sequence of SEQ ID NO: 97, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; X. (a) the amino acid sequence of SEQ ID NO: 98, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; XI. (a) the amino acid sequence of SEQ ID NO: 99, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; XII. (a) the amino acid sequence of SEQ ID NO: 100, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; XIII. (a) the amino acid sequence of SEQ ID NO: 109, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; and XIV. (a) the amino acid sequence of SEQ ID NO: 110, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; The composition of any of the above sequences, optionally wherein one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

[0240] 2. A composition comprising an scFv-Fab Fc antibody specific for claudin 6 and CD3, wherein the antibody: (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i.) SEQ ID NO: 80; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or (ii.) SEQ ID NO: 89; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; or (iii.) SEQ ID NO: 90; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 48 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; or (iv.) SEQ ID NO: 91, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 49 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; or (v.) SEQ ID NO: 92, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; or (vi.) SEQ ID NO: 111, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; and (c) a first light chain selected from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; The composition of any of the above sequences, optionally wherein one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

[0241] 3. The composition of embodiment 2, wherein said Fc is from IgG.

[0242] 4. The composition of embodiment 3, wherein the IgG is human IgG.

[0243] 5. The composition of embodiment 4, wherein the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0244] 6. The composition of any one of embodiments 2 to 5, wherein said antibody is formed via knobs-in-holes interactions in the Fc region.

[0245] 7. The composition of embodiment 4 or embodiment 5, wherein said human IgG Fc comprises one or more mutations to promote knobs-in-holes interactions.

[0246] 8. The composition of embodiment 7, wherein the mutation is selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V.

[0247] 9. The mutation is: (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V 8. The composition of embodiment 7, selected from:

[0248] 10. The composition of embodiment 4, wherein said human IgG Fc comprises one or more mutations to reduce or eliminate effector functions of the Fc domain.

[0249] 11. The composition of embodiment 10, wherein the mutation is a L234A and L235A (LALA) substitution in human IgG1.

[0250] 12. The composition of embodiment 4, wherein said human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain.

[0251] 13. The composition of embodiment 12, wherein the mutation is S228P.

[0252] 14. A composition comprising an IgG-(scFV)2 antibody specific for claudin 6 and CD3, wherein the antibody: (a) a heavy chain chosen from: (i.) SEQ ID NO: 86; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (ii.) SEQ ID NO: 87; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (iii.) SEQ ID NO: 101; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; (iv.) SEQ ID NO: 102, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; (v.) SEQ ID NO: 103, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; (vi.) SEQ ID NO: 104, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; (vii.) SEQ ID NO: 105; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; (viii.) SEQ ID NO: 106, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; (ix.) SEQ ID NO: 107, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; (x.) SEQ ID NO: 108, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; (xi.) SEQ ID NO: 112, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; (xii.) SEQ ID NO: 113, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; and (b) a light chain chosen from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; The composition of any of the above sequences, optionally wherein one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

[0253] 15. The composition of embodiment 14, wherein the Fc is derived from IgG.

[0254] 16. The composition of embodiment 15, wherein the IgG is human IgG.

[0255] 17. The composition of embodiment 16, wherein the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0256] 18. The composition of embodiment 16, wherein the human IgG Fc comprises one or more mutations to reduce or eliminate effector functions of the Fc domain.

[0257] 19. The composition of embodiment 18, wherein the mutations are L234A and L235A (LALA) substitutions in human IgG1.

[0258] 20. The composition of embodiment 16, wherein the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain.

[0259] 21. The composition of embodiment 20, wherein the mutation is S228P.

[0260] 22. A composition comprising an scFv-Fab Fc antibody specific for claudin 6 and CD3, wherein the antibody: (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: SEQ ID NO: 81, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; and (c) a light chain chosen from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66 an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; The composition of any of the above sequences, optionally wherein one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

[0261] 23. The composition of embodiment 22, wherein the Fc is derived from IgG.

[0262] 24. The composition of embodiment 23, wherein the IgG is human IgG.

[0263] 25. The composition of embodiment 24, wherein the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0264] 26. The composition of any one of embodiments 22-25, wherein the antibody is formed via knobs-in-holes interactions in the Fc region.

[0265] 27. The composition of embodiment 24, wherein said human IgG Fc comprises one or more mutations to promote knobs-in-holes interactions.

[0266] 28. The composition of embodiment 27, wherein the mutation is selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V.

[0267] 29. The mutation is: (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V 25. The composition of embodiment 24, wherein

[0268] 30. The composition of embodiment 24, wherein the human IgG Fc comprises one or more mutations to reduce or eliminate effector functions of the Fc domain.

[0269] 31. The composition of embodiment 30, wherein the mutation is a L234A and L235A (LALA) substitution in human IgG1.

[0270] 32. The composition of embodiment 24, wherein the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain.

[0271] 33. The composition of embodiment 32, wherein the mutation is S228P.

[0272] 34. A composition comprising an scFv-Fab Fc antibody specific for claudin 6 and CD3, wherein the antibody: (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i.) SEQ ID NO: 117, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (ii.) SEQ ID NO: 119; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (iii.) SEQ ID NO: 118; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iv.) SEQ ID NO: 120; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; and (c) a light chain chosen from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; The composition of any of the above sequences, optionally wherein one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

[0273] 35. The composition of embodiment 34, wherein the Fc is derived from IgG.

[0274] 36. The composition of embodiment 35, wherein the IgG is human IgG.

[0275] 37. The composition of embodiment 36, wherein the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0276] 38. The composition of any one of embodiments 34 to 37, wherein the antibody is formed via knobs-in-holes interactions in the Fc region.

[0277] 39. The composition of embodiment 36, wherein said human IgG Fc comprises one or more mutations to promote knobs-in-holes interactions.

[0278] 40. The composition of embodiment 39, wherein the mutation is selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V.

[0279] 41. The mutation is: (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V 37. The composition of embodiment 36, wherein

[0280] 42. The composition of embodiment 36, wherein the human IgG Fc comprises one or more mutations to reduce or eliminate effector functions of the Fc domain.

[0281] 43. The composition of embodiment 42, wherein the mutation is a L234A and L235A (LALA) substitution in human IgG1.

[0282] 44. The composition of embodiment 36, wherein the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain.

[0283] 45. The composition of embodiment 44, wherein the mutation is S228P.

[0284] 46. ​​A composition comprising an scFv-Fab Fc antibody specific for claudin 6 and CD3, wherein the antibody: (a) a first heavy chain selected from: (i) SEQ ID NO: 79; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i) SEQ ID NO: 121; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; (ii) SEQ ID NO: 123; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; (iii) SEQ ID NO: 125; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; (iv) SEQ ID NO: 127, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; (v) SEQ ID NO: 129, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; and (c) a first light chain selected from: (i) SEQ ID NO: 67; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; and (d) a second light chain selected from: (i) SEQ ID NO: 122; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; or (ii) SEQ ID NO: 124; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; or (iii) SEQ ID NO: 126; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; or (iv) SEQ ID NO: 128, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; or (v) SEQ ID NO: 130, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N- or C-terminus; The composition of any of the above sequences, optionally wherein one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

[0285] 47. The composition of embodiment 46, wherein the Fc is derived from IgG.

[0286] 48. The composition of embodiment 47, wherein the IgG is human IgG.

[0287] 49. The composition of embodiment 48, wherein the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0288] 50. The composition of any one of embodiments 46-49, wherein the antibody is formed via knobs-in-holes interactions in the Fc region.

[0289] 51. The composition of embodiment 46, wherein said human IgG Fc comprises one or more mutations to promote knobs-in-holes interactions.

[0290] 52. The composition of embodiment 51, wherein the mutation is selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V.

[0291] 53. The mutation is: (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1; T366W / K392C and T366S / L368A / D399C / Y407V, S354C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and S354C / T366S / L368A / Y407V, E356C / T366W and Y349C / T366S / L368A / Y407V, Y349C / T366W and E356C / T366S / L368A / Y407V, E357C / T366W and Y349C / T366S / L368A / Y407V, or Y349C / T366W and E357C / T366S / L368A / Y407V 52. The composition of embodiment 51, wherein

[0292] 54. The composition of embodiment 46, wherein the human IgG Fc comprises one or more mutations to reduce or eliminate effector functions of the Fc domain.

[0293] 55. The composition of embodiment 54, wherein the mutation is a L234A and L235A (LALA) substitution in human IgG1.

[0294] 56. The composition of embodiment 46, wherein the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain.

[0295] 57. The composition of embodiment 56, wherein the mutation is S228P.

[0296] 58. The composition of any one of embodiments 1 to 57, wherein the composition simultaneously binds to claudin 6 and CD3.

[0297] 59. The composition of any one of embodiments 1-58, wherein the composition binds to claudin 6 with an affinity of less than 10 nM and with an affinity that is at least 100-fold greater than claudin 9, claudin 3, and / or claudin 4.

[0298] 60. A pharmaceutical composition comprising an isolated antibody according to any one of embodiments 1 to 59 or a nucleic acid molecule encoding same.

[0299] 61. The pharmaceutical composition according to embodiment 60, wherein the composition is an injectable pharmaceutical composition.

[0300] 62. The pharmaceutical composition according to embodiment 60 or 61, wherein the composition is sterile.

[0301] 63. The pharmaceutical composition of any one of embodiments 60-62, wherein the composition is pyrogen-free.

[0302] 64. A nucleic acid molecule encoding the antibody or amino acid sequence of any of the preceding embodiments.

[0303] 65. A vector comprising the nucleic acid molecule of embodiment 64.

[0304] 66. A cell comprising a nucleic acid molecule according to embodiment 64 or a vector according to embodiment 65.

[0305] 67. A method for modulating and / or targeting claudin 6 and CD3 in biological cells, comprising contacting the cells with a composition described in any one of embodiments 1 to 59.

[0306] 68. A method for modulating claudin 6 activity in biological cells, comprising contacting a cell expressing claudin 6 with a composition described in any one of embodiments 1 to 59.

[0307] 69. A method for inhibiting the function of claudin 6 in biological cells, comprising contacting cells expressing claudin 6 with a composition described in any one of embodiments 1 to 59.

[0308] 70. A method for treating or preventing cancer, comprising administering to a subject in need thereof an effective amount of the composition described in any one of embodiments 1 to 59.

[0309] 71. Use of a composition according to any one of embodiments 1 to 59 for the preparation of a medicament for treating or preventing cancer.

[0310] 72. The cancer is basal cell carcinoma, biliary tract cancer, bladder cancer, bone cancer, brain and central nervous system cancer, breast cancer, peritoneal cancer, cervical cancer, choriocarcinoma, colorectal cancer, connective tissue cancer, digestive system cancer, endometrial cancer, esophageal cancer, eye cancer, head and neck cancer, gastric cancer (including gastrointestinal cancer), glioblastoma, glioma, liver cancer, hepatocellular carcinoma, intraepithelial neoplasia, kidney cancer or renal carcinoma, laryngeal cancer, leukemia, liver cancer, lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma), epithelial carcinoma), melanoma, myeloma, neuroblastoma, oral cancer (lip, tongue, mouth, and pharynx), ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, malignant rhabdoid tumor, rectal cancer, respiratory system cancer, salivary gland cancer, sarcoma, skin cancer, squamous cell carcinoma, stomach cancer, testicular cancer, thyroid cancer, uterine or endometrial cancer, urinary system cancer, vulvar cancer, lymphoma (including Hodgkin's lymphoma and non-Hodgkin's lymphoma, and B-cell lymphoma ( 72. The method or use of any one of embodiments 1-71, wherein the lymphoma is selected from one or more of: low-grade / follicular non-Hodgkin's lymphoma (NHL), small lymphocytic (SL) NHL, intermediate-grade / follicular NHL, intermediate-grade diffuse NHL, high-grade immunoblastic NHL, high-grade lymphoblastic NHL, high-grade small non-cleaved cell NHL, bulky mass disease NHL, mantle cell lymphoma, AIDS-related lymphoma, and Waldenstrom's macroglobulinemia), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, chronic myeloblastic leukemia, and other carcinomas and sarcomas, and post-transplant lymphoproliferative disorder (PTLD), and abnormal blood vessel proliferation associated with nevus syndrome, edema (e.g., associated with brain tumors), and Meigs syndrome.

[0311] 73. An isolated antibody comprising one or more of the sequences disclosed herein.

[0312] 74. A bispecific antibody comprising three polypeptides: A first polypeptide comprising a first light chain comprising a first variable light chain region, wherein the first variable light chain region comprises: (1) a CDR1 sequence comprising the amino acid sequence of SEQ ID NO: 1 or a variant thereof; (2) a CDR2 sequence comprising the amino acid sequence of SEQ ID NO: 2 or a variant thereof; and (3) the first polypeptide comprising a CDR3 sequence comprising the amino acid sequence of SEQ ID NO: 3 or a variant thereof; a second polypeptide comprising a first heavy chain comprising a first variable heavy chain region, said first variable heavy chain region comprising: (1) CDR1 comprising the amino acid sequence of SEQ ID NO: 4 or a variant thereof; (2) CDR2 comprising the amino acid sequence of SEQ ID NO: 5 or a variant thereof; and (3) the second polypeptide comprising a CDR3 comprising the amino acid sequence of SEQ ID NO: 6 or a variant thereof; a third polypeptide comprising a second light chain and a second heavy chain, wherein the second heavy chain comprises: (1) CDR1 comprising the amino acid sequence of SEQ ID NO: 25 or a variant thereof; (2) CDR2 comprising the amino acid sequence of SEQ ID NO: 26 or a variant thereof; and (3) a second variable heavy chain region comprising a CDR3 comprising the amino acid sequence of SEQ ID NO: 27, or a variant thereof; the second light chain (1) CDR1 comprising the amino acid sequence of SEQ ID NO: 28 or a variant thereof; (2) the amino acid sequence of SEQ ID NO: 29 or a variant thereof as CDR2, and (3) the third polypeptide comprising a second variable light chain region comprising a CDR3 comprising the amino acid sequence of SEQ ID NO: 30 or a variant thereof.

[0313] 75. The bispecific antibody of embodiment 74, wherein the first variable light chain region comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0314] 76. The bispecific antibody of embodiment 74 or 75, wherein the first light chain comprises the first variable light chain region and a light chain constant domain.

[0315] 77. The bispecific antibody of embodiment 76, wherein the first light chain constant domain comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0316] 78. The bispecific antibody of any one of embodiments 74 to 77, wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0317] 79. The bispecific antibody of any one of embodiments 74-78, wherein the first variable heavy chain region comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0318] 80. The bispecific antibody of any one of embodiments 74-79, wherein the first heavy chain comprises a first heavy chain variable region and a first heavy chain constant domain.

[0319] 81. The bispecific antibody of embodiment 80, wherein the first heavy chain c...

Claims

1. A bispecific antibody that binds to CLDN6 and CD3, A first polypeptide comprising a first light chain comprising a first variable light chain region, said first variable light chain region comprising: (1) a CDR1 sequence comprising the amino acid sequence of SEQ ID NO: 1; (2) a CDR2 sequence comprising the amino acid sequence of SEQ ID NO: 2; and (3) the first polypeptide comprising a CDR3 sequence comprising the amino acid sequence of SEQ ID NO: 3; a second polypeptide comprising a first heavy chain comprising a first variable heavy chain region, said first variable heavy chain region comprising: (1) CDR1 comprising the amino acid sequence of SEQ ID NO: 4; (2) CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and (3) the second polypeptide comprising a CDR3 comprising the amino acid sequence of SEQ ID NO: 6; and a third polypeptide comprising a second light chain and a second heavy chain, the second heavy chain (1) CDR1 comprising the amino acid sequence of SEQ ID NO: 25; (2) CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and (3) a second variable heavy chain region comprising a CDR3 comprising the amino acid sequence of SEQ ID NO: 27; the second light chain (1) CDR1 comprising the amino acid sequence of SEQ ID NO: 28; (2) CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and (3) the third polypeptide comprising a second variable light chain region comprising a CDR3 comprising the amino acid sequence of SEQ ID NO: 30 or a variant thereof.

2. 2. The bispecific antibody of claim 1 , wherein the first variable light chain region comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

68.

3. 2. The bispecific antibody of claim 1 , wherein the first variable light chain region comprises the amino acid sequence of SEQ ID NO:

68.

4. 2. The bispecific antibody of claim 1 , wherein the first variable heavy chain region comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

69.

5. 5. The bispecific antibody of claim 4, wherein the first variable heavy chain region comprises the amino acid sequence of SEQ ID NO:

69.

6. 2. The bispecific antibody of claim 1 , wherein the second variable heavy chain region comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

70.

7. 2. The bispecific antibody of claim 1 , wherein the second variable heavy chain region comprises the amino acid sequence of SEQ ID NO:

70.

8. The bispecific antibody of claim 1 , wherein the second variable heavy chain region and the second variable light chain region are linked by a peptide linker.

9. The bispecific antibody of claim 8, wherein the linker comprises the amino acid sequence of SEQ ID NO:

53.

10. 2. The bispecific antibody of claim 1, wherein the third polypeptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

89.

11. 2. The bispecific antibody of claim 1, wherein the third polypeptide has the amino acid sequence of SEQ ID NO:

89.

12. 2. The bispecific antibody of claim 1, wherein the first polypeptide further comprises a first constant domain and the third polypeptide further comprises a second constant domain.

13. The bispecific antibody of claim 12 , wherein the first constant domain and the second domain interact with each other to form a heterodimer.

14. 13. The bispecific antibody of claim 12, wherein the first constant domain and the second constant domain each independently comprise a human IgG Fc domain comprising one or more mutations.

15. i. the first constant domain comprises a T366W mutation and the second constant domain comprises T366S, L368A, and Y407V mutations; ii. the first constant domain comprises a T366Y and Y407T mutation or a T366Y and F405A mutation, and the second constant domain comprises a T394W and Y407T mutation; iii. the first constant domain comprises T366W and D399C mutations, and the second constant domain comprises T366S, L368A, K392C, and Y407V mutations; iv. the first constant domain comprises T366W and K392C mutations and the second constant domain comprises T366S, L368A, D399C, and Y407V mutations; v. the first constant domain comprises S354C and T366W mutations and the second constant domain comprises Y349C, T366S, L368A, and Y407V mutations; vi. the first constant domain comprises Y349C and T366W mutations and the second constant domain comprises S354C, T366S, L368A, and Y407V mutations; vii. the first constant domain comprises E356C and T366W mutations and the second constant domain comprises Y349C, T366S, L368A, and Y407V mutations; viii. the first constant domain comprises Y349C and T366W mutations, and the second constant domain comprises E356C, T366S, L368A, and Y407V mutations; ix. the first constant domain comprises E357C and T366W mutations and the second constant domain comprises Y349C, T366S, L368A, and Y407V mutations; or x. the first constant domain comprises Y349C and T366W mutations and the second constant domain comprises E357C, T366S, L368A, and Y407V mutations; 15. The bispecific antibody of claim 14, wherein the numbering is according to EU numbering for human IgG1.

16. 16. The bispecific antibody of claim 15, wherein the first constant domain comprises a T366W mutation and the second constant domain comprises T366S, L368A, and Y407V mutations, wherein the numbering is according to EU numbering for human IgG1.

17. 17. The bispecific antibody of claim 16, wherein the first constant domain and the second constant domain comprise L234A and L235A (LALA) substitutions, and the numbering is according to EU numbering for human IgG1.

18. the first polypeptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:67; the second polypeptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 79; 2. The bispecific antibody of claim 1, wherein the third polypeptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

89.

19. a first polypeptide comprising the amino acid sequence of SEQ ID NO: 67; a second polypeptide comprising the amino acid sequence of SEQ ID NO: 79; and and a third polypeptide comprising the amino acid sequence of SEQ ID NO:

89.

20. A pharmaceutical composition comprising the bispecific antibody of claim 1 and a pharmaceutically acceptable excipient.

21. 20. A pharmaceutical composition comprising the bispecific antibody of claim 18 and a pharmaceutically acceptable excipient.

22. 20. A pharmaceutical composition comprising the bispecific antibody of claim 19 and a pharmaceutically acceptable excipient.

23. A nucleic acid molecule or multiple nucleic acid molecules encoding the polypeptides of the bispecific antibody of claim 1.

24. 24. A cell comprising the nucleic acid molecule or molecules of claim 23.

25. 10. A method for treating cancer in a subject in need thereof, comprising administering to the subject the bispecific antibody of claim 1.

26. 20. A method for treating cancer in a subject in need thereof, comprising administering to the subject the bispecific antibody of claim 19.

27. 27. The method of claim 26, wherein the cancer is non-small cell lung cancer (NSCLC), ovarian cancer, gastric cancer, breast cancer, endometrial cancer, or testicular cancer.

28. 1. A composition comprising a tandem single chain variable fragment (scFv) specific for claudin 6 and CD3, wherein the scFv comprises: I. (a) the amino acid sequence of SEQ ID NO: 82, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 8 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 10 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 11 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 12 or a variant thereof; II. (a) the amino acid sequence of SEQ ID NO: 83, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 8 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 10 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 11 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 12 or a variant thereof; III. (a) the amino acid sequence of SEQ ID NO: 84, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; and (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; IV. (a) the amino acid sequence of SEQ ID NO: 85, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; and (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; V. (a) the amino acid sequence of SEQ ID NO: 93, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; VI. (a) the amino acid sequence of SEQ ID NO: 94, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; VII. (a) the amino acid sequence of SEQ ID NO: 95, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; VIII. (a) the amino acid sequence of SEQ ID NO: 96, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; IX. (a) the amino acid sequence of SEQ ID NO: 97, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; X. (a) the amino acid sequence of SEQ ID NO: 98, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; XI. (a) the amino acid sequence of SEQ ID NO: 99, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; XII. (a) the amino acid sequence of SEQ ID NO: 100, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; XIII. (a) the amino acid sequence of SEQ ID NO: 109, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; and XIV. (a) the amino acid sequence of SEQ ID NO: 110, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or (b) (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; and (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N- or C-terminus; The composition, wherein in any of the above sequences, optionally one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

29. A composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, the antibody comprising: (a) a first heavy chain selected from: (i) SEQ ID NO: 79, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i.) SEQ ID NO: 80, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or (ii.) SEQ ID NO: 89; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; or (iii.) SEQ ID NO: 90; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 48 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; or (iv.) SEQ ID NO: 91, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 49 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; or (v.) SEQ ID NO: 92, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; or (vi.) SEQ ID NO: 111, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; and (c) a first light chain selected from: (i) SEQ ID NO: 67, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N- or C-terminus; The composition, wherein in any of the above sequences, optionally one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

30. Claudin-6 and CD3-specific IgG-(scFv) ２ A composition comprising an antibody, the antibody comprising: (a) a heavy chain selected from: (i.) SEQ ID NO: 86, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (ii.) SEQ ID NO: 87; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (iii.) SEQ ID NO: 101, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; (iv.) SEQ ID NO: 102, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; (v.) SEQ ID NO: 103, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; (vi.) SEQ ID NO: 104, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; (vii.) SEQ ID NO: 105, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; (viii.) SEQ ID NO: 106, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; (ix.) SEQ ID NO: 107, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; (x.) SEQ ID NO: 108, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; (xi.) SEQ ID NO: 112, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; (xii.) SEQ ID NO: 113, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; and (b) a light chain selected from: (i) SEQ ID NO: 67, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N- or C-terminus; The composition, wherein in any of the above sequences, optionally one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

31. A composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, the antibody comprising: (a) a first heavy chain selected from: (i) SEQ ID NO: 79, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: SEQ ID NO: 81, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; and (c) a light chain selected from: (i) SEQ ID NO: 67, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66 an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N- or C-terminus; The composition, wherein in any of the above sequences, optionally one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

32. A composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, the antibody comprising: (a) a first heavy chain selected from: (i) SEQ ID NO: 79, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i.) SEQ ID NO: 117, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (ii.) SEQ ID NO: 119; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; (iii.) SEQ ID NO: 118, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (iv.) SEQ ID NO: 120, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; and (c) a light chain selected from: (i) SEQ ID NO: 67, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N- or C-terminus; The composition, wherein in any of the above sequences, optionally one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functional equivalent thereof.

33. A composition comprising an scFv-Fab Fc antibody specific for claudin-6 and CD3, the antibody comprising: (a) a first heavy chain selected from: (i) SEQ ID NO: 79, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof; (ii) SEQ ID NO: 88; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof; or (iii) SEQ ID NO: 114, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof; (b) a second heavy chain selected from: (i) SEQ ID NO: 121, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof; (ii) SEQ ID NO: 123; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof; (iii) SEQ ID NO: 125, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof; (iv) SEQ ID NO: 127, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof; (v) SEQ ID NO: 129, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof; and (c) a first light chain selected from: (i) SEQ ID NO: 67, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; (ii) SEQ ID NO: 66; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; or (iii) SEQ ID NO: 65, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof; and (d) a second light chain selected from: (i) SEQ ID NO: 122; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof; or (ii) SEQ ID NO: 124; an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof; or (iii) SEQ ID NO: 126, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof; or (iv) SEQ ID NO: 128, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; or (v) SEQ ID NO: 130, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto; or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; or Any of the above sequences in subsection (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N- or C-terminus; The composition, wherein in any of the above sequences, optionally one or more of the linkers comprising glycine and serine are replaced with another peptide linker or a functionally equivalent variation thereof.

34. The composition of any one of claims 29 to 33, wherein the composition simultaneously binds to claudin 6 and CD3.

35. 35. The composition of any one of claims 29 to 34, wherein the composition binds to claudin 6 with an affinity of less than 10 nM and with an affinity that is at least 100 times greater than claudin 9, claudin 3, and / or claudin 4.

36. A pharmaceutical composition comprising the isolated antibody of any one of claims 29 to 34 or a nucleic acid molecule encoding the antibody.

37. A nucleic acid molecule encoding the antibody or amino acid sequence of any one of claims 29 to 34.

38. A vector comprising the nucleic acid molecule of claim 37.

39. 39. A cell comprising the nucleic acid molecule of claim 37 or the vector of claim 38.

40. 35. A method for treating or preventing cancer, comprising administering to a subject in need thereof an effective amount of the composition of any one of claims 29 to 34.

41. Use of a bispecific antibody according to any one of claims 1 to 19 or a composition according to any one of claims 29 to 34 for the preparation of a medicament for treating cancer.

42. The cancer may be basal cell carcinoma, biliary tract cancer, bladder cancer, bone cancer, brain and central nervous system cancer, breast cancer, peritoneal cancer, cervical cancer, choriocarcinoma, colon cancer, connective tissue cancer, digestive system cancer, endometrial cancer, esophageal cancer, eye cancer, head and neck cancer, stomach cancer (including gastrointestinal cancer), glioblastoma, glioma, liver cancer, hepatocellular carcinoma, intraepithelial neoplasia, kidney or renal cancer, laryngeal cancer, leukemia, liver cancer, lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and squamous cell lung cancer), skin cancer), melanoma, myeloma, neuroblastoma, oral cancer (lip, tongue, mouth, and pharynx), ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, malignant rhabdoid tumor, rectal cancer, respiratory system cancer, salivary gland cancer, sarcoma, skin cancer, squamous cell carcinoma, stomach cancer, testicular cancer, thyroid cancer, uterine or endometrial cancer, urinary system cancer, vulvar cancer, lymphoma (including Hodgkin's lymphoma and non-Hodgkin's lymphoma, and B-cell lymphoma) 42. The method or use of claim 40 or 41, wherein the lymphoma is selected from one or more of the following: (including low-grade / follicular non-Hodgkin's lymphoma (NHL), small lymphocytic (SL) NHL, intermediate-grade / follicular NHL, intermediate-grade diffuse NHL, high-grade immunoblastic NHL, high-grade lymphoblastic NHL, high-grade small non-cleaved cell NHL, bulky mass disease NHL, mantle cell lymphoma, AIDS-related lymphoma, and Waldenstrom's macroglobulinemia), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, chronic myeloblastic leukemia, and other carcinomas and sarcomas; and post-transplant lymphoproliferative disorders (PTLDs); and abnormal blood vessel proliferation associated with phacomatosis, edema (e.g., associated with brain tumors), and Meigs' syndrome.

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