Humanized Anti-CDH17 antibodies and use of the same

Abstract

Described herein are antibody drug conjugates and Fc fusion proteins containing anti-CDH17 antibodies and the use of the same. Humanized anti-CDH17 antibodies provided herein exhibit improved characteristics.

Description

[0001]Attorney Docket No.55171.4008 / WO HUMANIZED ANTI-CDH17 ANTIBODIES AND USE OF THE SAME CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority of U.S. Provisional Application No. 63 / 680,227, filed on August 7, 2024, the contents of which are incorporated herein by reference in its entirety. BACKGROUND Antibody-drug conjugates (ADCs) are an innovative cancer immunotherapy approach that focuses on the selective delivery of cytotoxic payloads to tumors. Detailed descriptions of antibody-drug conjugates can be found in, for example, Tsuchikama et al., Nat Rev Clin Oncol 21, 203–223 (2024), Dumontet et al., Nat Rev Drug Discov, 22, 641-661 (2023), Fu et al., Sig Transduct Target Ther, 7, 93 (2022), and Khongorzul et al., Mol Cancer Res, 18, 3-19 (2020). By targeting surface antigen expressed on tumor cells, the antibodies have demonstrated efficacy in the targeting and killing of tumor cells. Cadherin 17 (CDH17) is a cell adhesion molecule that is expressed in the epithelium of the small intestine and colon. Abnormal expression of CDH17 is associated with gastrointestinal cancers including colorectal, gastric, pancreatic, and hepatocellular carcinomas and adenocarcinomas of the digestive system. There is a clinical need for ADCs and Fc fusion proteins containing novel CDH17 targeting antibodies for the treatment of cancers, inflammatory bowel diseases, and other CDH17-associated disease. SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The XML copy, created on August 05, 2025, is named “SL_55171_4008WO.xml” and is 200,597 bytes in size. SUMMARY In one aspect, provided herein is an antibody-drug conjugate comprising Formula (I): 1 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Ab-(L-D)n Formula (I), wherein: Ab binds human CDH17 and comprises an antibody or antigen-binding domain thereof comprising: (i) a humanized variant of SEQ ID NO: 109 comprising: (a) an HCDR1 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 41, (b) an HCDR2 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 47, (c) an HCDR3 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 72, and (d) a set of amino acid substitutions in framework region(s) of SEQ ID NO: 109 are selected from the group consisting of: V68I / Q74K / N83S / K85R / G90A, Q4V / T17L / S23A / F45L / Q112L, Q4V / T17L / F45L / Q112L, S59A / V68I / Q74K / N83S / K85R / G90A, Q4V / T17L / F45W / V68I / N83S / K85R / G90A / I91V, V68I / T73S / Q74K / N83S / K85R / G90A, Q4V / T17L / E42G / V68I / Q74K, V68I / N83S / K85R / G90A, Q4V / F45L, Q4V / T17L / F45W / V68I / N83S / G90A / I91V / Q112L, Q4V / T17L / E42G / K85R, Q4V / T17L / S23A / F45L, T17L / E42G / V68I / N83S / G90A, Q4V / T17L / V68I / N83S / G90A / Q112L, F45L / V68I, T17L / V68I / N83S / G90A, Q4V / F45L / Q112L, F45W / V68I / T73S / Q74K / N83S / K85R / G90A, F45W / V68I / Q74K / N83S / K85R / G90A, V68I / N83S / G90A, V68I / G90A, V68I / N83S, Q4V / T17L, Q4V, T17L, V68I, N83S, and G90A, wherein the N-terminus amino acid position of SEQ ID NO: 109 is position 0, (ii) an Fc domain; L is a sulfamide linker or a legumain-cleavable linker, wherein L is attached to an amino acid of a CH2 domain of the Fc domain; D is a cytotoxic agent or an anti-inflammatory agent; and n is a drug-to-antibody ratio (DAR), wherein the drug-to-antibody ratio is from about 1 to about 8. The conjugate of claim 1, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 41, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 47, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 72. In some embodiments, the set of amino acid substitutions in framework region(s) are selected from the group consisting of: (a) the set of amino acid substitutions in framework 3 (FR3), (b) the set of amino acid substitutions in FR1, FR2, and FR3, (c) the set of amino acid substitutions in FR1, FR2, and FR4, (d) the set of amino acid substitutions in FR1 and FR2, (e) the set of amino acid substitutions in FR1-FR4, (f) the set of amino acid substitutions in FR1, FR3, and FR4, (g) the set of amino acid substitutions in FR2 and FR3, and (h) the set of amino acid substitutions in FR1 and FR3. 2 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, the antibody or antigen-binding domain thereof comprises the set of amino acid substitutions of V68I / Q74K / N83S / K85R / G90A does not further comprise amino acid substitutions selected from the group consisting of: G71D, N78Y, T73S, F45W, S59A, G71D / N78Y, T73S / N78Y, G71D / T73S, F45W / G71D, F45W / N78Y, F45W / T73S, G71D / T73S / N78Y, F45W / G71D / N78Y, F45W / T73S / N78Y, F45W / T73D / N78Y, F45W / G71D / V77L, G71D / T73S / V77L / N78Y, G71D / T73S / V77L / P86A, G71D / V77L / N78Y / I91V, G71D / T73S / N78Y / I91V, G71D / T73S / V77L / I91V, F45W / G71D / N78Y / N78Y, F45W / G71D / V77L / N78Y, G71D / V77L / N78Y / I91V, G71D / T73S / V77L / N78Y / P86A, G71D / T73S / V77L / P86A / I91V, G71D / T73S / N78Y / P86A / I91V, G71D / V77L / N78Y / P86A / I91V, Q4V / T17L / S23A / E42G / I91V, S23A / F35V / G71D / N78Y / I91V, F45W / G71D / T73S / V77L / N78Y, T17L / R43L / F45W / G71D / V77L / I91V, Q0E / Q4V / T17L / G71D / T73A / V77L / I91V, T17L / S23A / E42G / R43L / F45W / G71D / V77L, Q0E / T17L / G71D / V77L / N78Y / S106Y / Q112L, S23A / F35V / R43L / F45W / G71D / N78Y / Q112L, Q4V / F35V / R43L / F45W / G71D / A101S / Q112L, Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / P86A, Q0E / Q4V / F35V / R43L / F45W / G71D / V77L / Q112L, Q0E / Q4V / T17S / S23A / T73A / V77L / P86A / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / P86A / Q112L, Q0E / Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / I91V, and Q0E / Q4V / T17LS23A / G71D / T73A / V77L / N78Y / Q112L. In some embodiments, the antibody or antigen-binding domain thereof comprises the set of amino acid substitutions of Q4V / T17L / S23A / F45L / Q112L does not further comprise amino acid substitutions selected from the group consisting of: R70L, V68I / Q74K, and V68I / Q74K / V77L / N83S / G90A. In some embodiments, the antibody or antigen-binding domain thereof comprises the set of amino acid substitutions of Q4V / T17L / F45L / Q112L does not further comprise amino acid substitutions selected from the group consisting of: S23A, S23A / R70L, S23A / V68I / Q74K, and S23A / V68I / Q74K / V77L / N83S / G90A. In some embodiments, the antibody or antigen-binding domain thereof comprises: an FR1 having an amino acid sequence QVQLZ1ESGGGLVQPGGSZ2RLSCVZ3SRTFSY 3 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO (SEQ ID NO: 128), wherein Z1is Q or V, Z2is T or L, and Z3is S or A, an FR2 having an amino acid sequence WFRQAPGKZ4REZ5VA (SEQ ID NO: 129), wherein Z4 is E or G, and Z5is F or L or W, an FR3 having an amino acid sequence RFTZ6SRGNZ7Z8NSVNLQMNZ9LZ10PEDTZ11Z12YYCAV (SEQ ID NO: 130), wherein Z6is V or I, Z7 is T or S, Z8 is Q or K, Z9 is N or S, Z10 is K or R, Z11 is G or A, and Z12 is I or V, and an FR4 having an amino acid sequence WGQGTZ13(SEQ ID NO: 131), wherein Z13is Q or L. In some embodiments, the antibody or antigen-binding domain thereof comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 110-128. In some embodiments, the antibody or antigen-binding domain thereof comprises an amino acid sequence of SEQ ID NO: 125. In some embodiments, the antibody or antigen-binding domain thereof comprises an amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody or antigen-binding domain thereof comprises an amino acid sequence of SEQ ID NO: 126. In some embodiments, the Fc domain is derived from IgA, IgD, IgE, IgG, or IgM. In some embodiments, the Fc domain is derived from IgG1, IgG2, or IgG4. In some embodiments, the Fc domain is derived from IgG1 or IgG4. In some embodiments, the Ab is a single-domain antibody or any polypeptide comprising the humanized variant of SEQ ID NO: 109. In some embodiments, the Ab comprises a VHH domain and an Fc domain based on IgG1 or IgG4. In some embodiments, the Ab comprises from N-terminus to C-terminus: a VHH domain that binds CDH17, a peptide linker, and an Fc domain based on IgG1 or IgG4. In some embodiments, the Ab comprises: a first monomer comprising a first humanized variant of SEQ ID NO: 109 and a first Fc domain, and a second monomer comprising a second humanized variant of SEQ ID NO:109 and a second Fc domain, thereby forming a homodimeric polypeptide. In some embodiments, the Ab comprises: a first monomer comprising a first humanized variant of SEQ ID NO: 109 and a first Fc domain, and a second monomer comprising a second humanized variant of SEQ ID NO:109 and a second Fc domain, thereby forming a heterodimeric polypeptide. 4 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments of the antibody-drug conjugate, the sulfamide linker or the legumain-cleavable linker is attached to an asparagine at position 297 of the CH2 domain of the Fc domain. In some embodiments, the sulfamide linker or the legumain-cleavable linker comprises one or more spacer moieties and a linker moiety. In some embodiments, the one or more spacer moieties each comprises a polar sulfamide and polyethyleneglycol (PEG). In some embodiments, the linker moiety comprises a cleavable linker. In some embodiments, the linker moiety comprises a non-cleavable linker. In some embodiments, the cleavable linker is a protease-cleavable linker. In some embodiments, the protease-cleavable linker is a cathepsin-cleavable linker. In some embodiments, the cathepsin-cleavable linker is a valine-citrulline linker. In some embodiments, the linker moiety further comprises a self-immolative spacer moiety. In some embodiments, the self-immolative spacer moiety is a p-aminocarbamate (PABC) spacer moiety. In some embodiments, the cytotoxic agent of the antibody-drug conjugate is selected from the group consisting of: toxin targeting ribosome, toxin targeting elongation factor, toxin targeting tubulin, toxin targeting DNA, toxin targeting RNA, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine (PBD) dimer, benzodiazepine, CC-1065 analogue, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracyl (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analog, DX-8951f, exatecan mesylate, duocarmycin derivative, amanitin, a-amanitin, spliceostatin, a thailanstatin, ozogamicin, Amberstatin269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), Monomethyl Auristatin D (MMAD), monomethyl dolastatin 10, Monomethyl Auristatin F (MMAF, mafodotin), N-methylvaline-valine- dolaisoleuine-dolaproine-phenylalanine, Monomethyl Auristatin E (MMAE), N- methylvaline-valine-dolaisoleuine-dolaproine-norephedrine, deruxtecan, tesirine, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, histone deacetylase inhibitors, PE38, SN-38, ENPP3, tubulysin, exatecan, STING agonist, TLR agonist, alpha-amanitin, SGD-1882, CC- 5 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 1065, and 5-benzoylvaleric acid-AE ester (AEVB). In some other embodiments, the cytotoxic agent is MMAE. In some embodiments, the anti-inflammatory agent is selected from the group consisting of: synthetic glucocorticoid, glucocorticoid analog, fluticasone furoate (FF), fluticasone propionate (FP), halobetasol propionate, clobetasol propionate, glucocorticoid receptor modulator (GRM), and any derivatives thereof. In some embodiments, the sulfamide linker further comprises one or more attachment groups. In some embodiments, the one or more attachment groups is selected from the group consisting of maleimide, caproic acid, and both. In some embodiments, n is about 4. In other words, in some embodiments, the antibody-drug conjugate is a DAR4 ADC. In other embodiments, the conjugate exhibits increased serum half-life compared to a control isotype conjugate. In some other embodiments, the conjugate exhibits increased tissue penetration compared to a control isotype conjugate. In some embodiments, the conjugate exhibits increased in vitro potency compared to a control isotype conjugate. In certain embodiments, the conjugate exhibits improved drug delivery to a target cell compared to a control isotype conjugate. In many embodiments, the conjugate exhibits reduced toxicity or nonspecific payload release to a subject upon administration as compared to a control isotype conjugate. In some embodiments, the conjugate exhibits increased in vivo potency or efficacy to a subject upon administration as compared to a control isotype conjugate. In some embodiments, the control isotype conjugate is a vedotin antibody-drug conjugate. In another aspect, provided herein is an anti-CDH17 Fc fusion protein comprising: (i) a humanized variant of SEQ ID NO: 109 comprising: (a) an HCDR1 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 41, (b) an HCDR2 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 47, (c) an HCDR3 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 72, and (d) a set of amino acid substitutions in framework region(s) of SEQ ID NO: 109 are selected from the group consisting of: V68I / Q74K / N83S / K85R / G90A, Q4V / T17L / S23A / F45L / Q112L, Q4V / T17L / F45L / Q112L, S59A / V68I / Q74K / N83S / K85R / G90A, Q4V / T17L / F45W / V68I / N83S / K85R / G90A / I91V, V68I / T73S / Q74K / N83S / K85R / G90A, Q4V / T17L / E42G / V68I / Q74K, 6 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO V68I / N83S / K85R / G90A, Q4V / F45L, Q4V / T17L / F45W / V68I / N83S / G90A / I91V / Q112L, Q4V / T17L / E42G / K85R, Q4V / T17L / S23A / F45L, T17L / E42G / V68I / N83S / G90A, Q4V / T17L / V68I / N83S / G90A / Q112L, F45L / V68I, T17L / V68I / N83S / G90A, Q4V / F45L / Q112L, F45W / V68I / T73S / Q74K / N83S / K85R / G90A, F45W / V68I / Q74K / N83S / K85R / G90A, V68I / N83S / G90A, V68I / G90A, V68I / N83S, Q4V / T17L, Q4V, T17L, V68I. N83S, and G90A, wherein the N-terminus amino acid position of SEQ ID NO: 109 is position 0, and (ii) an Fc domain. In some embodiments, the HCDR1 comprises the amino acid sequence of SEQ ID NO: 41, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 47, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 72. In other embodiments, the set of amino acid substitutions in framework region(s) are selected from the group consisting of: (a) the set of amino acid substitutions in framework 3 (FR3), (b) the set of amino acid substitutions in FR1, FR2, and FR3, (c) the set of amino acid substitutions in FR1, FR2, and FR4, (d) the set of amino acid substitutions in FR1 and FR2, (e) the set of amino acid substitutions in FR1-FR4, (f) the set of amino acid substitutions in FR1, FR3, and FR4, (g) the set of amino acid substitutions in FR2 and FR3, and (h) the set of amino acid substitutions in FR1 and FR3. In some embodiments, the set of amino acid substitutions in framework region(s) comprising V68I / Q74K / N83S / K85R / G90A does not further comprise amino acid substitutions selected from the group consisting of: G71D, N78Y, T73S, F45W, S59A, G71D / N78Y, T73S / N78Y, G71D / T73S, F45W / G71D, F45W / N78Y, F45W / T73S, G71D / T73S / N78Y, F45W / G71D / N78Y, F45W / T73S / N78Y, F45W / T73D / N78Y, F45W / G71D / V77L, G71D / T73S / V77L / N78Y, G71D / T73S / V77L / P86A, G71D / V77L / N78Y / I91V, G71D / T73S / N78Y / I91V, G71D / T73S / V77L / I91V, F45W / G71D / N78Y / N78Y, F45W / G71D / V77L / N78Y, G71D / V77L / N78Y / I91V, G71D / T73S / V77L / N78Y / P86A, G71D / T73S / V77L / P86A / I91V, G71D / T73S / N78Y / P86A / I91V, G71D / V77L / N78Y / P86A / I91V, Q4V / T17L / S23A / E42G / I91V, S23A / F35V / G71D / N78Y / I91V, F45W / G71D / T73S / V77L / N78Y, T17L / R43L / F45W / G71D / V77L / I91V, Q0E / Q4V / T17L / G71D / T73A / V77L / I91V, T17L / S23A / E42G / R43L / F45W / G71D / V77L, Q0E / T17L / G71D / V77L / N78Y / S106Y / Q112L, S23A / F35V / R43L / F45W / G71D / N78Y / Q112L, 7 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Q4V / F35V / R43L / F45W / G71D / A101S / Q112L, Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / P86A, Q0E / Q4V / F35V / R43L / F45W / G71D / V77L / Q112L, Q0E / Q4V / T17S / S23A / T73A / V77L / P86A / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / P86A / Q112L, Q0E / Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / I91V, and Q0E / Q4V / T17LS23A / G71D / T73A / V77L / N78Y / Q112L. In some embodiments, the set of amino acid substitutions in framework region(s) comprising Q4V / T17L / S23A / F45L / Q112L does not further comprise amino acid substitutions selected from the group consisting of: R70L, V68I / Q74K, and V68I / Q74K / V77L / N83S / G90A. In other embodiments, the set of amino acid substitutions in framework region(s) comprising Q4V / T17L / F45L / Q112L does not further comprise amino acid substitutions selected from the group consisting of: S23A, S23A / R70L, S23A / V68I / Q74K, and S23A / V68I / Q74K / V77L / N83S / G90A. In some embodiments, the set of amino acid substitutions in framework region(s) comprises: an FR1 having an amino acid sequence QVQLZ1ESGGGLVQPGGSZ2RLSCVZ3SRTFSY (SEQ ID NO: 128), wherein Z1is Q or V, Z2 is T or L, and Z3 is S or A, an FR2 having an amino acid sequence WFRQAPGKZ4REZ5VA (SEQ ID NO: 129), wherein Z4is E or G, and Z5is F or L or W, an FR3 having an amino acid sequence RFTZ6SRGNZ7Z8NSVNLQMNZ9LZ10PEDTZ11Z12YYCAV (SEQ ID NO: 130), wherein Z6is V or I, Z7 is T or S, Z8 is Q or K, Z9 is N or S, Z10 is K or R, Z11 is G or A, and Z12 is I or V, and an FR4 having an amino acid sequence WGQGTZ13 (SEQ ID NO: 131), wherein Z13 is Q or L. In some embodiments, the anti-CDH17 Fc fusion protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 110-128. In some embodiments, the anti-CDH17 Fc fusion protein comprises an amino acid sequence of SEQ ID NO: 125. In certain embodiments, the anti-CDH17 Fc fusion protein comprises an amino acid sequence of SEQ ID NO: 123. In other embodiments, the anti-CDH17 Fc fusion protein comprises an amino acid sequence of SEQ ID NO: 126. 8 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, the Fc domain is derived from IgA, IgD, IgE, IgG, or IgM. In other embodiments, the Fc domain is derived from IgG1, IgG2, or IgG4. In some other embodiments, the Fc domain is derived from IgG1 or IgG4. In certain embodiments, the anti-CDH17 Fc fusion protein comprises from N- terminus to C-terminus: a VHH domain comprising the humanized variant of SEQ ID NO: 109, and the Fc domain comprises an Fc domain based on IgG1 or IgG4. In some embodiments, the anti-CDH17 Fc fusion protein comprises from N-terminus to C-terminus: a VHH domain comprising the humanized variant of SEQ ID NO: 109, a peptide linker, and the Fc domain comprises an Fc domain based on IgG1 or IgG4. In some embodiments, the anti-CDH17 Fc fusion protein comprises an amino acid sequence of any one of SEQ ID NOS: 145, 147, and 148. In some embodiments, the anti- CDH17 Fc fusion protein comprises SEQ ID NO: 147. In some other embodiments, the anti- CDH17 Fc fusion protein comprises SEQ ID NO: 145. In other embodiments, the anti- CDH17 Fc fusion protein comprises SEQ ID NO: 148. In certain embodiments, the anti-CDH17 Fc fusion protein comprises: a first monomer from N-terminus to C-terminus comprising a first humanized variant of SEQ ID NO: 109 and a first Fc domain of human IgG, and a second monomer from N-terminus to C- terminus comprising a second humanized variant of SEQ ID NO:109 and a second Fc domain of human IgG, thereby forming a homodimeric polypeptide. In some embodiments, the anti-CDH17 Fc fusion protein comprises: a first monomer from N-terminus to C-terminus comprising a first humanized variant of SEQ ID NO: 109 and a first Fc domain of human IgG, and a second monomer from N-terminus to C-terminus comprising a second humanized variant of SEQ ID NO:109 and a second Fc domain of human IgG, thereby forming a heterodimeric polypeptide. In many embodiments, the anti-CDH17 Fc fusion protein comprises a first monomer comprises any one of SEQ ID NOS: 132-150, and a second monomer comprises any one of SEQ ID NOS: 132-150. In other embodiments, the anti-CDH17 Fc fusion protein comprises a first monomer comprises SEQ ID NOS: 145, 147, and 148, and a second monomer comprises SEQ ID NOS: 145, 147, and 148. In some embodiments, the anti-CDH17 Fc fusion protein comprises the first monomer comprises SEQ ID NO: 147, and the second monomer comprises SEQ ID NO: 147. In some other embodiments, the anti-CDH17 Fc fusion protein 9 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO comprises the first monomer comprises SEQ ID NO: 145, and the second monomer comprises SEQ ID NO: 145. In other embodiments, the anti-CDH17 Fc fusion protein comprises the first monomer comprises SEQ ID NO: 148, and the second monomer comprises SEQ ID NO: 148. In another aspect, provided herein is an anti-CDH17 antibody-drug conjugate comprising Formula (I): Ab-(L-D)n Formula (I), wherein: Ab binds human CDH17 and comprises from the N-terminus to C-terminus: a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72 and a set of amino acid substitutions of V68I / Q74K / N83S / K85R / G90A in framework region 3, wherein the N- terminus amino acid position of SEQ ID NO: 109 is position 0; a linker of SEQ ID NO: 101; and an Fc domain of human IgG1; L comprises a polar sulfamide polyethyleneglycol chain connected to Val-Cit-p-aminobenzyloxycarbonyl (vc-PABC), wherein L is attached to the N297 of the CH2 domain of the Fc domain; D is MMAE; and n is 4. In yet another aspect, provided herein is an anti-CDH17 antibody-drug conjugate comprising Formula (I): Ab-(L-D)n Formula (I), wherein: Ab binds human CDH17 and comprises from the N-terminus to C-terminus: a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72 and a set of amino acid substitutions of Q4V / T17L / S23A / F45L / Q112L in framework regions 1, 2, and 4, wherein the N-terminus amino acid position of SEQ ID NO: 109 is position 0; a linker of SEQ ID NO: 101; and an Fc domain of human IgG1; L comprises a polar sulfamide polyethyleneglycol chain connected to Val-Cit-p-aminobenzyloxycarbonyl (vc-PABC), wherein L is attached to the N297 of the CH2 domain of the Fc domain; D is MMAE; and n is 4. In one aspect, provided herein is an anti-CDH17 antibody-drug conjugate comprising Formula (I): Ab-(L-D)n Formula (I), wherein: Ab binds human CDH17 and comprises from the N-terminus to C-terminus: a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an 10 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72 and a set of amino acid substitutions of Q4V / T17L / F45L / Q112L in framework regions 1, 2, and 4, wherein the N- terminus amino acid position of SEQ ID NO: 109 is position 0; a linker of SEQ ID NO: 101; and an Fc domain of human IgG1; L comprises a polar sulfamide polyethyleneglycol chain connected to Val-Cit-p-aminobenzyloxycarbonyl (vc-PABC), wherein L is attached to the N297 of the CH2 domain of the Fc domain; D is MMAE; and n is 4. In one aspect, provided herein is an anti-CDH17 Fc fusion protein comprising from the N-terminus to C-terminus: (a) a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72, and a set of amino acid substitutions of V68I / Q74K / N83S / K85R / G90A in framework region 3, wherein the N-terminus amino acid position of SEQ ID NO: 109 is position 0; (b) a linker of SEQ ID NO: 101; and (c) an Fc domain of human IgG1; wherein the anti-CDH17 Fc fusion protein binds human CDH17. In another aspect, provided herein is an anti-CDH17 Fc fusion protein comprising from the N-terminus to C-terminus: (a) a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72, and a set of amino acid substitutions of Q4V / T17L / S23A / F45L / Q112L in framework regions 1, 2, and 4, wherein the N-terminus amino acid position of SEQ ID NO: 109 is position 0; (b) a linker of SEQ ID NO: 101; and (c) an Fc domain of human IgG1; wherein the anti-CDH17 Fc fusion protein binds human CDH17. In another aspect, provided herein is an anti-CDH17 Fc fusion protein comprising from the N-terminus to C-terminus: (a) a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72, and a set of amino acid substitutions of Q4V / T17L / F45L / Q112L in framework regions 1, 2, and 4, wherein the N-terminus amino acid position of SEQ ID NO: 109 is position 0; (b) a linker of SEQ ID NO: 101; and (c) an Fc domain of human IgG1; wherein the anti-CDH17 Fc fusion protein binds human CDH17. Provided herein is an anti-CDH17 Fc fusion protein comprises an amino acid sequence of SEQ ID NO: 147. Also provided herein is an anti-CDH17 Fc fusion protein comprising two monomers each comprising an amino acid sequence of SEQ ID NO: 147. Also provided herein is an anti-CDH17 Fc fusion protein comprises an amino acid sequence 11 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO of SEQ ID NO: 148. Provided herein is an anti-CDH17 Fc fusion protein comprising two monomers each comprising an amino acid sequence of SEQ ID NO: 148. Also provided herein is an anti-CDH17 Fc fusion protein comprises an amino acid sequence of SEQ ID NO: 145. Provided herein is an anti-CDH17 Fc fusion protein comprising two monomers each comprising an amino acid sequence of SEQ ID NO: 145. Provided herein is an anti-CDH17 VHH antigen binding domain comprises an amino acid sequence of SEQ ID NO: 125. Provided herein is an anti-CDH17 VHH antigen binding domain comprises an amino acid sequence of SEQ ID NO: 126. Also provided herein is an anti-CDH17 VHH antigen binding domain comprises an amino acid sequence of SEQ ID NO: 123. Provided also is one or more nucleic acids encoding any of the anti-CDH17 antibody- drug conjugates described herein, any of the anti-CDH17 Fc fusion proteins described, or any of the anti-CDH17 VHH antigen binding domains described. Provided also is an expression vector comprising any of the one or more nucleic acids described such as the nucleic acids encoding any of the anti-CDH17 antibody-drug conjugates, any of the anti-CDH17 Fc fusion proteins, or any of the anti-CDH17 VHH antigen binding domains. Provided is a host cell comprising any of the one or more nucleic acids described or the expression vector described. In one aspect, disclosed is a method of producing an anti-CDH17 antibody-drug conjugate, an anti-CDH17 Fc fusion protein, or an anti-CDH17 VHH antigen binding domain, comprising: (a) maintaining the host cell described herein in a medium to produce the anti-CDH17 antibody-drug conjugate, the anti-CDH17 Fc fusion protein, or the anti- CDH17 VHH antigen binding domain, (b) isolating the anti-CDH17 antibody-drug conjugate, the anti-CDH17 Fc fusion protein, or the anti-CDH17 VHH antigen binding domain produced by the host cell, and optionally (c) purifying the anti-CDH17 antibody-drug conjugate, the anti-CDH17 Fc fusion protein, or the anti-CDH17 VHH antigen binding domain. In one aspect, disclosed is a pharmaceutical composition for treating cancer comprising any of the anti-CDH17 antibody-drug conjugates described herein, any of the anti-CDH17 Fc fusion proteins described, or any of the anti-CDH17 VHH antigen binding domains described, and a pharmaceutically acceptable carrier or excipient. 12 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, the pharmaceutical composition also comprises at least one additional therapeutic agent. In some embodiments, the at least one additional therapeutic agent comprises T cell-engaging immunotherapy, CAR-T therapy, or a small molecule therapy. In one aspect, disclosed is a kit comprising (a) any of the anti-CDH17 antibody-drug conjugates described herein, any of the anti-CDH17 Fc fusion proteins described, or any of the anti-CDH17 VHH antigen binding domains described, and (b) instructions for use. In one aspect, provided is a method for treating cancer comprising administering to a human subject with cancer any of the anti-CDH17 antibody-drug conjugates described herein, any of the anti-CDH17 Fc fusion proteins described herein, any of the anti-CDH17 VHH antigen binding domains described, or any of the pharmaceutical composition described herein. In some embodiments, the cancer is selected from the group consisting of CDH17- positive cancer gastrointestinal cancer, pancreatic cancer, neuroendocrine cancer, liver cancer, and colorectal cancer. In another aspect, provided is a method for treating an inflammatory bowel disease (IBD) comprising administering to a human subject with IBD any of the anti-CDH17 antibody-drug conjugates described herein, any of the anti-CDH17 Fc fusion proteins described herein, any of the anti-CDH17 VHH antigen binding domains described, or any of the pharmaceutical composition described herein. In some embodiments, the inflammatory bowel disease is selected from the group consisting of Ulcerative Colitis, Crohn’s Disease, microscopic colitis, and eosinophilic GI disorder. BRIEF DESCRIPTION OF THE DRAWINGS The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “Fig.,” “FIG.,” “Figure,” “Figures,” “Figs.,” and “FIGs.” herein) of which: FIG.1 depicts the potency of BHB156-SYNstatin, a control isotype SYNstatin (an anti-SARS-COV-2 VHH-Fc SYNstatin), and BHB-vedotin in clearing tumor biomass in 13 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO SNU16 (gastric cancer) cell line-derived xenograft (CDX) tumor-bearing mice in a repeat dose study. FIG.2 depicts the potency of SYNstatin and vedotin in clearing tumor biomass in SNU16 (gastric cancer) cell line-derived xenograft (CDX) tumor-bearing mice with descending doses in a single dose study. FIG.3 depicts the potency of BHB156-SYNstatin, BHB156-vedotin, isotype- SYNstatin, and isotype-vedotin in clearing tumor biomass in SW403 (colorectal cancer) cell line-derived xenograft (CDX) tumor-bearing mice in a repeat dose study. FIG.4 depicts the potency of BHB156-SYNstatin, BHB156-vedotin, isotype- SYNstatin, and isotype-vedotin in clearing tumor biomass in AsPC1 (pancreatic adenocarcinoma) cell line-derived xenograft (CDX) tumor-bearing mice in a repeat dose study. FIGS.5A and 5B, FIGS.6A and 6B, FIGS.7A and 7B, and FIG.8 each show representative in vitro cancer cell drug sensitivity plots against a SNU16 cancer cell line for a series of humanized anti-CDH17 ADCs (humanized anti-CDH17 VHH-Fc fusion proteins conjugated to oYo-linked MMAE; DAR2) compared to a control anti-CDH17-VHH-Fc fusion protein ADC (BHB156-oyo-linked MMAE). FIG.9 shows monovalent binding kinetics of an exemplary humanized anti-CDH17 antibody to His-tagged human CDH17 antigen. FIG.10 shows monovalent binding kinetics of an exemplary humanized anti-CDH17 antibody to His-tagged rat CDH17 antigen. FIG.11 and FIG.12 show antibody purity of an exemplary humanized anti-CDH17 antibody (BHB810 VHH-Fc) as assessed by SDS-PAGE electrophoresis (FIG.11) and size exclusion chromatography (SEC-HPLC) (FIG.12). FIG.13 depicts cell binding kinetics of an exemplary humanized anti-CDH17 antibody (BHB810 VHH-Fc antibody) to SNU16 cells as compared to a control anti-CDH17 antibody (BHB156 VHH-Fc antibody). FIG.14 depicts peripheral antibody clearance in plasma of an exemplary BHB810- SYNstatin in non-tumor-bearing nude mice as measured by ELISA. 14 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO FIG. 15 depicts anti-tumor activity of an exemplary BHB810-SYNstatin in SNU16tumor-bearing nude mice. FIG. 16 illustrates in-house AI / ML platform-driven optimization of anti-CDH17VHH affinity across sequential design rounds. Each design round (DR) consists of 90 unique sequence variants. Note that the DR rounds were immediately sequential (i.e., DR03 gave rise to DR05, which gave rise to DR08), despite non-sequential numbering. FIG. 17 shows variants generated during de-immunization / humanization of theaffinity-optimized anti-CDH17 VHH. FIG.17 (left) shows that several rounds of de- immunization revealed a tradeoff between decreasing in silico immunogenicity risk, as measured by increased OASis percentile or derisked percentage, and successful synthesis and binding. FIG.17 (right) shows that successful variants had a range of affinities, stabilities and decreased immunogenicity risk. FIG. 18 shows predicted MHC-II 9-mers. Y-values represent the fraction of all MHC-II alleles that are predicted to bind to the 9-mer in the 5th or lower percentile of all possible peptides, where lower percentile indicates higher confidence. In the solid trace, the predicted MHC-II epitopes for the affinity-optimized VHH are plotted as a sliding window of 9-mer derivatives of the primary sequence. In the dashed trace, the predicted MHC-II epitopes of the de-immunized affinity-optimized VHH are plotted. A threshold of 20% predicted allele binding was selected as significant based on prior literature. Row 4 (below solid trace) hashes represent the CDRs, antibody icons represent 9-mers found in clinical stage IgGs row 3 hashes represent 9-mers that are identical to human germline Ig sequences, row 2 hashes represent 9-mer sequences found in clinical-stage VHHs, and row 1 (bottom row above x- axis) hashes represent 9-mers found in human proteins. The antibody icons represent 9-mers found in clinical stage IgGs. FIG. 19 depicts derisked peptide percentage vs. ADA incidence in clinical studies.Derisked peptide percentage is shown for each Fv in clinical-stage VHH antibodies vs. percent of patients who developed anti-drug antibodies in studies. Dashed line shows the percent of derisked 9-mer peptides for BHB810. FIG. 20 depicts humanness assessment of BHB810 (SEQ ID NOS: 155-159),showing the percent of 9-mers found in 50% or more of human patients in OAS (“OASis 15 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO identity”) and the percent sequence identity with the nearest human heavy chain (“germline content”). FIGS.21A, 21B, 21C, and 21D show biophysical analysis of conjugated BHB810. FIG.21A provides intact mass spectrometry analysis of conjugated BHB810. FIG.21B provides SDS-PAGE of conjugated BHB810 under non-reducing (left) and reducing (right) conditions. Lanes 1-3 depict the sample pre-conjugation, post-remodeling, and post- conjugation, respectively. FIG.21C shows monomeric purity analysis of BHB810 as measured by analytical SEC. FIG.21D shows RP-UPLC determination of DAR in the conjugated molecule. FIG. 22 depicts cell binding data of BHB810 to SNU16 CDH17+ cells by flowcytometry affinities of un-conjugated and SYNstatin-conjugated BHB810 as measured by BLI. Shown are the binding curves (top) and fitted kinetic parameters (table) of BHB810 and BHB810-SYNstatin against human and rat CDH17. FIG. 23 depicts a steady state kinetics model of BHB810 bound to hFcRn by BLI.The KD is 4.73E-07 M with R2of 0.977 and Rmax of 0.1034. Binding was measured at pH 6.0. FIG. 24 depicts cell binding data of BHB810 to SNU16 CDH17+ cells by flowcytometry. FIGS.25A, 25B, and 25C show biophysical analysis of unconjugated BHB810. FIG. 25A shows monomeric purity of BHB810 after 1-step ProA purification as measured by SEC. FIG.25B shows an SDS-PAGE of BHB810 under reducing (R) and non-reducing (N-R) conditions. FIG.25C provides thermostability analysis of BHB810 as measured by intrinsic fluorescence (Tm, top) and SLS (Tagg, bottom). Shown are both curves from the duplicate loadings. FIGS.26A, 26B, and 26C show purity analysis of BHB810 following 1h low pH and 7d 40°C incubations. Indicated are monomeric purities of untreated (FIG.26A), low pH- incubated (FIG.26B), and 40°C-incubated (FIG.26C) BHB810 as measured by SEC. FIGS.27A, 27B, 27C, 27D, and 27E depict purity analysis of conjugated BHB810 following 3X freeze / thaw, 7d 40°C incubation, and 3w 25°C incubation conditions; all traces show 100% monomeric purity. Conditions are as follows: (FIG.27A) untreated (FIG.27B) 16 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 1X freeze / thaw (FIG.27C) 3X freeze / thaw (FIG.27D) 1w at 40°C and (FIG.27E) 21d at 25°C. FIGS.28A, 28B, and 28C show polyreactivity analysis of BHB810 using cell-based flow cytometry, antigen-based ELISA, and BVP ELISA. FIG.28A depicts normalized polyreactivity scores of SYNstatin- and unconjugated BHB156 and BHB810 against the cell lines as indicated. Included in the testing is Bococizumab, a known high-polyreactivity control. The dotted line indicates a cutoff score of 2. FIG.28B depicts summed-fold-over- PBS-score of SYNstatin- and unconjugated BHB156 and BHB810 relative to known low- and high-polyreactivity controls Adalimumab and Bococizumab. The dotted line indicates a cut-off score of 12. FIG.28C depicts results of an BVP ELISA ran against SYNstatin- and unconjugated BHB156 and BHB810 with high-polyreactivity control Bococizumab as comparison. The dotted line indicates a cutoff score of 5. FIG.29 depicts in vitro potency data for payload-conjugated BHB810 and BHB156. Cell viabilities of SNU16 (140K copies / cell) after a 96h incubation with MMAE-conjugated BHB156 (DAR 2) and BHB810 (DAR 2). The compounds achieve IC50s of 235 pM and 295 pM, respectively. FIG.30 depicts results of PK studies of SYNstatin-conjugated BHB156 and BHB810 in non-tumor bearing nude mice. Time-dependent plasma concentrations of test articles up to 96h post injection with half-lives as indicated in the data legend. FIG.31 depicts in vivo efficacy of BHB810-SYNstatin. Activity of SYNstatin- conjugated BHB810 in a nude mice SNU-16 CDX model. Plotted are average tumor volumes from mice injected with SYNstatin-conjugated BHB810 at the time points post-injection as indicated relative to an isotype control. DETAILED DESCRIPTION The description is presented to enable one of ordinary skill in the art to make and use the invention and is provided in the context of a patent application and its requirements. The section headings used herein are for organization purposes only and are not to be construed as limiting the subject matter described. While various embodiments of the invention(s) of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, 17 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO changes, and substitutions may occur to those skilled in the art without departing from the invention(s). It should be understood that various alternatives to the embodiments of the invention(s) described herein may be employed in practicing any one of the inventions(s) set forth herein. All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. I. Overview In some aspects, provided are antibody-drug conjugates comprising any of the anti- CDH17 antibodies or antigen-binding domains thereof and linker-payload constructs described herein. Also provided are any of the anti-CDH17 antibodies or antigen-binding domains thereof described herein. In some embodiments, the anti-CDH17 antibodies or antigen-binding domains thereof described herein are single-domain antibodies such as a VHH antibody, a VHH-Fc antibody, or a VHH-Fc homodimer antibody. In some embodiments, the anti-CDH17 antibodies or antigen-binding domains thereof are described in WO 2024 / 163630 and US Application No.19 / 151,550, the contents including the figures and sequence listings are hereby incorporated by reference in their entirety. Also provided are method of producing anti-CDH17 antibody-drug conjugates, anti-CDH17 antibodies or antigen-binding domains thereof, and anti-CDH17 single-domain antibodies such as VHH antibodies, VHH-Fc antibodies, or VHH-Fc homodimer antibodies. Also provides are methods of treating cancer or an inflammatory bowel disease by administering any of the anti-CDH17 molecules described. II. Definitions Unless defined otherwise, technical, and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. For purposes of the present disclosure, the following terms are defined below. The definitions provided are intended to apply to a given term, as well as other derivative linguistic re-phrasings and grammatical equivalents of the term. The terminology used herein is for the purpose of describing particular cases only and is not intended to be limiting. In this application, the use of the singular includes the plural 18 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO unless specifically stated otherwise. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. In this application, the use of “or” means “and / or” unless stated otherwise. The terms “and / or” and “any combination thereof” and their grammatical equivalents as used herein, can be used interchangeably. These terms can convey that any combination is specifically contemplated. Solely for illustrative purposes, the following phrases “A, B, and / or C” or “A, B, C, or any combination thereof” can mean “A individually; B individually; C individually; A and B; B and C; A and C; and A, B, and C.” The term “or” can be used conjunctively or disjunctively, unless the context specifically refers to a disjunctive use. The term “about” or “approximately” can mean within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” can mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, “about” can mean a range of up to 20%, up to 15%, up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, within 5- fold, or within 2-fold, of a value. Where particular values are described in the application and claims, unless otherwise stated the term “about” meaning within an acceptable error range for the particular value should be assumed. As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the present disclosure, and vice versa. Furthermore, compositions of the present disclosure can be used to achieve methods of the present disclosure. Reference in the specification to “some embodiments,” “an embodiment,” “one embodiment” or “other embodiments” means that a particular feature, structure, or characteristic described in connection with the embodiments is included in at least some 19 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO embodiments, but not necessarily all embodiments, of the present disclosures. To facilitate an understanding of the present disclosure, a number of terms and phrases are defined below. Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50, as well as all intervening decimal values between the aforementioned integers such as, for example, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, and 1.9. With respect to sub-ranges, “nested sub-ranges” that extend from either end point of the range are specifically contemplated. For example, a nested sub-range of an exemplary range of 1 to 50 may comprise 1 to 10, 1 to 20, 1 to 30, and 1 to 40 in one direction, or 50 to 40, 50 to 30, 50 to 20, and 50 to 10 in the other direction. The term “cadherin 17,” “cadherin-17,” “CDH-17,” or “CDH17” refer to a membranous cell adhesion protein that is expressed by cells in the gastrointestinal tract and pancreas, including intestinal epithelial cells. CDH17 is also known as liver-intestine cadherin, LI-cadherin, LI cadherin, cadherin-16, human intestinal peptide-associated transporter HPT-1, human peptide transporter 1, intestinal peptide-associated transporter HPT-1, and HPT-1 cadherin. The CDH17 protein is a cadherin-like protein including an extracellular region, containing 7 cadherin domains, and a transmembrane region but lacking a cadherin conserved cytoplasmic domain. Amino acid sequences of human CDH17 and portions thereof can be found in several sources including UniProt Ref. No. Q12864 and NCBI Ref. Nos. NP_001138135.1, NP_001400880.1, NP_001400881.1, NP_001400883.1, NP_001400884.1, NP_001400885.1, NP_001400886.1, NP_001400887.1, NP_001400888.1, NP_001400889.1, NP_001400890.1 and NP_004054.3. Nucleic acid sequences of human CDH17 can be found in several sources NCBI Ref. Nos. NM_001144663.2, NM_001413951.1, NM_001413952.1, NM_001413953.1, NM_001413954.1, NM_001413955.1, NM_001413956.1, NM_001413957.1, NM_001413958.1, NM_001413959.1, NM_001413960.1, NM_001413961.1, and NM_004063. Amino acid sequences of mouse CDH17 and portions thereof can be found in several sources including UniProt Ref. No. Q9R100 and NCBI Ref. No. NP_062727. Nucleic acid sequences of mouse CDH17 and portions thereof can be found in several sources including NCBI Ref. No. NM_019753.4. CDH17 positive cells have been detected in various human tumor types, 20 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO including but not limited to, colorectal cancer, gastric cancer, pancreatic cancer, liver cancer, epithelial and neuroendocrine colorectal neoplasms, other gastrointestinal adenocarcinomas, esophageal adenocarcinomas, mucinous ovarian cancer, pancreatic acinar cell carcinoma, cervical adenocarcinoma, bilio-pancreatic adenocarcinomas, other neuroendocrine neoplasms, and pulmonary adenocarcinomas. Expression of CDH17 in human cancers has been described in, for example, Jacobsen et al., Pathol, Res Pract, 2024 April, 256:155175; Panarelli et al., American Journal of Clinical Pathology, Volume 138, Issue 2, August 2012, Pages 211–222. The term “pharmaceutically acceptable” refers to approved or approvable by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia (U.S.P.) or other generally recognized pharmacopeia for use in animals, including humans. A “pharmaceutically acceptable excipient, carrier or diluent” refers to an excipient, carrier or diluent that can be administered to a subject, together with an agent, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the agent. A “pharmaceutically acceptable salt” suitable for the disclosure may be an acid or base salt that is generally considered in the art to be suitable for use in contact with the tissues of human beings or animals without excessive toxicity, irritation, allergic response, or other problem or complication. Such salts include mineral and organic acid salts of basic residues such as amines, as well as alkali or organic salts of acidic residues such as carboxylic acids. Specific pharmaceutical salts include, but are not limited to, salts of acids such as hydrochloric, phosphoric, hydrobromic, malic, glycolic, fumaric, sulfuric, sulfamic, sulfanilic, formic, toluenesulfonic, methanesulfonic, benzene sulfonic, ethane disulfonic, 2-hydroxyethyl sulfonic, nitric, benzoic, 2-acetoxybenzoic, citric, tartaric, lactic, stearic, salicylic, glutamic, ascorbic, pamoic, succinic, fumaric, maleic, propionic, hydroxymaleic, hydroiodic, phenylacetic, alkanoic such as acetic, HOOC-(CH2)n-COOH where n is 0-4, and the like. Similarly, pharmaceutically acceptable cations include, but are not limited to sodium, potassium, calcium, aluminum, lithium and ammonium. Those of ordinary skill in the art will recognize from this disclosure and the knowledge in the art that further pharmaceutically acceptable salts include those listed by Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, PA, p.1418 (1985). In general, a pharmaceutically acceptable acid or base salt can be synthesized from a parent compound that contains a basic or acidic moiety by any 21 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO conventional chemical method. Briefly, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in an appropriate solvent. The term “subject” refers to an animal which is the object of treatment, observation, or experiment. By way of example only, a subject includes, but is not limited to, a mammal, including, but not limited to, a human or a non-human mammal, such as a non-human primate, bovine, equine, canine, ovine, or feline. As used herein, “non-canonical” amino acids can refer to amino acid residues in D- or L-form that are not among the 20 canonical amino acids generally incorporated into naturally occurring proteins. Unless otherwise specified, a “nucleotide sequence encoding a protein” includes all nucleotide sequences that are degenerate versions of each other and thus encode the same amino acid sequence. The term “optional” or “optionally” denotes that a subsequently described event or circumstance can but need not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. The term “exogenous” refers to any material introduced from or originating from outside a cell, a tissue or an organism that is not produced by or does not originate from the same cell, tissue, or organism in which it is being introduced. The term “nucleic acid” refers to a deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), or a combination thereof, in either a single- or double-stranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogues of natural nucleotides that have similar binding properties as the reference nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses complementary sequences as well as the sequence explicitly indicated. In some embodiments of any of the nucleic acids described herein, the nucleic acid is DNA. In some embodiments of any of the nucleic acids described herein, the nucleic acid is RNA. Modifications can be introduced into a nucleotide sequence by standard techniques known in the art, such as site-directed mutagenesis and polymerase chain reaction (PCR)- mediated mutagenesis. Conservative amino acid substitutions are ones in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of 22 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., arginine, lysine and histidine), acidic side chains (e.g., aspartic acid and glutamic acid), uncharged polar side chains (e.g., asparagine, cysteine, glutamine, glycine, serine, threonine, tyrosine, and tryptophan), nonpolar side chains (e.g., alanine, isoleucine, leucine, methionine, phenylalanine, proline, and valine), beta-branched side chains (e.g., isoleucine, threonine, and valine), and aromatic side chains (e.g., histidine, phenylalanine, tryptophan, and tyrosine), and aromatic side chains (e.g., histidine, phenylalanine, tryptophan, and tyrosine). The term “antigen-binding domain” is used to refer to one or more antibody variable domain(s) (e.g., formed from amino acids from a single polypeptide or formed from amino acids from two or more polypeptides (e.g., the same or different polypeptides) that is capable of specifically binding to one or more different antigen(s). In some examples, an antigen- binding domain can bind to an antigen or epitope with specificity and affinity similar to that of naturally-occurring antibodies. In some embodiments, the antigen-binding domain can be an antibody or a fragment thereof. In some embodiments, an antigen-binding domain can include an alternative scaffold. Non-limiting examples of antigen-binding domains are described herein. Additional examples of antigen-binding domains are known in the art. Unless otherwise specified, a “nucleotide sequence encoding a protein” includes all nucleotide sequences that are degenerate versions of each other and thus encode the same amino acid sequence. The term “antibody” refers to a protein with an immunoglobulin fold that specifically binds to an antigen via its variable region or regions. The term “antibody” is used herein in the broadest sense and encompasses monoclonal antibodies, polyclonal antibodies, dimers, multimers, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired biological activity (Miller et al., J. Immunol.170:4854-4861, 2003). Antibodies may be murine, human, humanized, chimeric, or derived from other species. (Janeway, C., Travers, P., Walport, M., Shlomchik (2001) Immunol. Biology, 5th Ed., Garland Publishing, New York). A target antigen generally has numerous binding sites, also called epitopes, recognized by CDRs (complementarity determining regions) on multiple antibodies. Each antibody that specifically binds to a different epitope has a different structure. Thus, one antigen may have more than one corresponding antibody. An antibody can, e.g., include a full-length immunoglobulin molecule or an immunologically active 23 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO portion of a full-length immunoglobulin molecule, i.e., a molecule that contains an antigen- binding site that immunospecifically binds an antigen of a target of interest or part thereof. The immunoglobulin disclosed herein can be of any type (e.g., IgG, IgE, IgM, IgD, and IgA), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclass of immunoglobulin molecule. The immunoglobulins can be derived from any species. In one aspect, however, the immunoglobulin is of human, murine, or rabbit origin. In some embodiments, the antibody or antigen-binding domain thereof is a single domain antibody, a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a grafted antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fvs (scFv), a single chain antibody, a Fab fragment, a F(ab′)2 fragment, a Fd fragment, a Fv fragment, a single-domain antibody, a diabody, a fragment comprised of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), an intrabody, an anti-idiotypic (anti-Id) antibody, a VHH antibody, or ab antigen- binding domains thereof. An antibody, antibody fragment, or antigen binding domain is capable of binding to its specific target or antigen. Furthermore, an antibody, antibody fragment, or antigen binding domain according to the invention comprises the minimum structural requirements of an antibody which allow for the target binding. This minimum requirement may, e.g. be defined by the presence of at least the three heavy chain CDRs (i.e. CDR1, CDR2 and CDR3 of the VH region) and / or the three light chain CDRs (i.e. CDR1, CDR2 and CDR3 of the VL region). In some embodiments of a single-domain antibody such as a VHH antibody, the minimum structural requirement for target antigen binding includes the three heavy chain CDRs (i.e. HCDR1, HCDR2, and HCDR3). The antibodies according to the invention are based include for example monoclonal, recombinant, chimeric, deimmunized, humanized and human antibodies. The term “humanized” or “de-immunized” in the context of an antibody, antibody thereof, and an antigen binding domain refers to an antibody, antibody thereof, and an antigen binding domain obtained from a non-human species and modified to contain more human sequence(s) and minimal non-human sequence(s) compared to the antibody, antibody thereof, and an antigen binding domain of the non-human species. In some embodiments, the sequence modifications made refine and optimize the activity or performance of the antibody. In some embodiments, the humanized antibody can be generated by replacing sequences in a 24 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO variable domain that is not directly involved in antigen binding with equivalent sequences from an similar or equivalent human domain. A humanized antibody can be optimized by the introduction of conservative substitutions, consensus sequence substitutions, germline substitutions and / or back mutations. The term “antigen binding domain,” “antigen-binding domain” or “ABD” refers to a portion of a full-length antibody or a polypeptide that includes a portion of a full-length antibody, and that retains antigen-binding activity via its variable region or regions. Examples of antigen-binding domains include VHH domains, Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies; minibodies (Olafsen et al., Protein Eng. Design & Sel.17(4):315-323, 2004), fragments produced by a Fab expression library, single chain antibody molecules including VH, VL, and VHH domains, and multispecific antibodies formed from antigen-binding domains. The term “complementarity determining region” or “CDR” refers to one of the three hypervariable regions that are known to confer (at least in part) antigen-binding specificity in each antibody light chain and each antibody heavy. The three CDRs in the antibody heavy chain and the antibody light chain interrupt four framework regions in the heavy chain variable domain and the light chain variable domain. The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3, numbered sequentially starting from the N-terminus, and are also typically identified by the chain in which the particular CDR is located. For instance, the heavy chain complementarity determining regions can be sequentially referred to as HCDR1, HCDR2, and HCDR3 and light chain complementarity determining regions can be sequentially referred to as LCDR1, LCDR2, and LCDR3. Also, the heavy chain framework regions can be sequentially referred to as HFR1, HFR2, HFR3 and HFR4 and light chain framework regions can be sequentially referred to as LFR1, LFR2, LFR3 and LFR4. In some embodiments, an antibody comprises an amino acid sequence of a heavy chain variable region according to the formula: HFR1-HCDR1-HFR2-HCDR2-HFR3- HCDR3-HFR4, and an amino acid sequence of a light chain variable region is according to the formula LFR1-LCDR1-LFR2-LCDR2-LFR3-LCDR3-LFR4. In some embodiments, a single domain antibody comprises an amino acid sequence of a heavy chain variable region according to the formula: HFR1-HCDR1-HFR2-HCDR2-HFR3-HCDR3-HFR4. 25 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO The framework regions or FRs of different light immunoglobulin chains and different heavy immunoglobulin chains are relatively conserved within different antibodies produced by a mammal. The framework regions of light and heavy immunoglobulin chains serve to position and align the CDRs in three-dimensional space. Framework sequences can be obtained from public DNA databases or published references that include germline antibody gene sequences. For example, germline DNA sequences for human heavy and light chain variable region genes can be found in the “VBASE2” germline variable gene sequence database for human and mouse sequences. An "amino acid substitution" refers to the replacement of at least one existing amino acid residue in a predetermined amino acid sequence with another different "replacement" amino acid residue. The replacement residue or residues may be "naturally occurring amino acid residues" (i.e. encoded by the genetic code) and selected from the group consisting of: alanine (Ala or A); arginine (Arg or R); asparagine (Asn or N); aspartic acid (Asp or D); cysteine (Cys or C); glutamine (Gln or Q); glutamic acid (Glu or E); glycine (Gly or G); histidine (His or H); isoleucine (Ile or I): leucine (Leu or L); lysine (Lys or K); methionine (Met or M); phenylalanine (Phe or F); proline (Pro or P); serine (Ser or S); threonine (Thr or T); tryptophan (Trp or W); tyrosine (Tyr or Y); and valine (Val or V). The term “administer” refers to a method of delivering compositions to the desired site of biological action. These methods include, but are not limited to, topical delivery, parenteral delivery, intravenous delivery, intradermal delivery, subcutaneous delivery, intramuscular delivery, colonic delivery, rectal delivery, or intraperitoneal delivery. The terms “identical” or percent “identity,” in the context of two or more polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues, e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% or greater, that are identical over a specified region when compared and aligned for maximum correspondence over a comparison window or designated region, as measured using a sequence comparison algorithm or by manual alignment and visual inspection. For sequence comparison of polypeptides, typically one amino acid sequence acts as a reference sequence, to which a candidate sequence is compared. Alignment can be performed using various methods available to one of skill in the art, e.g., visual alignment or using publicly available software using known algorithms to achieve maximal alignment. 26 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Such programs include the BLAST programs, ALIGN, ALIGN-2 or Megalign. The parameters employed for an alignment to achieve maximal alignment can be determined by one of skill in the art. For sequence comparison of polypeptide sequences for purposes of this application, the BLASTP algorithm standard protein BLAST for aligning two proteins sequence with the default parameters is used. The term “affinity” refers to the strength of the sum of all non-covalent interactions between an antigen-binding site and its antigen. Unless otherwise indicated, “affinity” refers to intrinsic binding affinity, which reflects a 1:1 interaction between an antigen-binding domain and an antigen. Affinity can be measured, e.g., using surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®). Additional methods for determining the affinity of an antigen-binding domain and its antigen are known in the art. The term “single-chain polypeptide” means a polypeptide comprising a single polypeptide chain. The term “multi-chain polypeptide” means a complex of two or more (e.g., 2, 3, 4, 5, 6, 7, or 8) polypeptide chains (e.g., the same or different polypeptide chains) that covalently and / or non-covalently associate with each other. For example, two or more polypeptide chains of a multi-chain polypeptide can associate through the use of two domains that associate with each other (e.g., two Fc domains or IL-15 and the sushi domain of IL-15 receptor alpha). The term “variable domain residue numbering as in Kabat” or “amino acid position numbering as in Kabat”, and variations thereof, refers to the numbering system used for heavy chain variable domains or light chain variable domains of the compilation of antibodies in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991). Using this numbering system, the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a FR or CDR of the variable domain. The Kabat numbering of residues may be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a “standard” Kabat numbered sequence. It will be apparent to those skilled in the art that there are alternative numbering conventions for amino acid residues in variable domain sequences and full-length antibody sequences. There 27 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO are also alternative numbering conventions for CDR sequences, for example those set out in Chothia et al. (1989) Nature 342:877-883. Other numbering conventions for CDR sequences available to a skilled person include “AbM” (University of Bath) and “contact” (university College London) methods. The minimum overlapping region using at least two of the Kabat, Chothia, AbM and contact methods can be determined to provide the ‘minimum binding unit’. The minimum binding unit may be a sub-portion of a CDR. Table 1 below represents one definition using each numbering convention for each CDR or binding unit. The Kabat numbering scheme is used in Table 1 to number variable domain amino acid sequence. It should be noted that some of the CDR definition may vary depending on the individual publication used. Table 1 KABAT CDR CHOTHIA ABM CDR CONTACT MINIMUM CDR CDR BINDING , bound or linked to another component. For example, a “moiety of a cytotoxic agent” refers to a cytotoxic agent that is covalently linked to one or more groups such as a linker (L2), which itself can be optionally further linked to an antibody via linker (L1). The term “glycan,” as used herein, refers to a monosaccharide, polysaccharide, or oligosaccharide chain that can be connected to a protein such as an antibody or antigen- binding domain thereof. In some instances, a glycan is attached to a protein via the C-1 carbon of one sugar, which may be without further substitution (monosaccharide) or may be further substituted at one or more of its hydroxyl groups (oligosaccharide or polysaccharide). 28 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO An oligosaccharide can be linear or branched. A glycan can be an N-linked glycan, O-linked glycan, or a C-linked glycan. The term “conjugation linker” or “linker” refers to a moiety that connects or links two or more components of, for example, an antibody-drug conjugate (ADC). In an ADC, a conjugation linker covalently attaches an antibody and a payload to each other. In some embodiments, a conjugation linker can include one or more linkers, one or more spacers, and any combination thereof. The term “spacer” refers to a moiety that connects or conjugates components of an ADC. In some embodiments, a spacer connects an antibody to a linker, a part of a linker to another part of the linker, a linker to a payload, and the like. The term “sulfamide linker” refers to a linker comprising a sulfamide group, more particularly an acylsulfamide group [—C(O)—N(H)—S(O)2—N(R′)—] and / or a carbamoyl sulfamide group [—O—C(O)—N(H)—S(O)2—N(R′)—]. The terms “payload,” “drug payload,” and “warhead,” as used interchangeably herein, refers to a chemical or biological moiety that is conjugated (e.g., covalently attached) to an antibody or antigen-binding domain, and can include any therapeutic or diagnostic agent, for example, but not limited to, cytotoxic agents, both for cancer and for non-cancer indications. As used herein, the term “about” a value (or parameter) refers to ±10% of a stated value. When referring to a range of values (or parameters), the term “about” refers to +10% of the upper limit and -10% of the lower limit of a stated range of values. When a range of values is provided, it is to be understood that each intervening value between the upper and lower limit of that range, and any other stated or intervening value in that stated range, is encompassed within the scope of the present disclosure. Where the stated range includes upper and / or lower limits, ranges excluding either of those included limits are also included in the present disclosure. It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. All combinations of the embodiments pertaining to the disclosure are specifically embraced by the present disclosure and are disclosed herein just as if each and every combination was individually and explicitly disclosed. In addition, all sub- combinations of the various embodiments and elements thereof are also specifically 29 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO embraced by the present disclosure and are disclosed herein just as if each and every such sub-combination was individually and explicitly disclosed herein. III. Anti-CDH17 Antibody-Drug Conjugates Described herein are antibody-drug conjugates (ADCs) that bind cadherin 17 (CDH17) antigens. In some embodiments, the CDH17 antigen is a human CDH17 antigen. In other embodiments, the CDH17 antigen is a non-human CDH17 antigen. In some embodiments, the anti-CDH17 ADC binds an epitope of human CDH17. In some embodiments, the anti-CDH17 ADC comprises an antibody, antibody fragment thereof, or antigen-binding domain thereof that binds an extracellular domain of human CDH17. In further embodiments, the anti-CDH17 ADC comprises any antibody, antibody fragment thereof, or antigen-binding domain thereof that binds an extracellular domain of human CDH17 described herein. Provided herein is a humanized antibody, fragment thereof, or antigen-binding domain thereof that specifically binds CDH17 comprising the amino acid sequence of SEQ ID NO: 109 and a set of amino acid modifications (substitutions, additions, and / or deletions) in one or more of the framework regions, such as FR1-FR4. In some aspect, provided are anti-CDH17 ADCs that contain any humanized antibody, fragment thereof or antigen binding domain thereof described herein. In some embodiments, the humanized antibody, fragment thereof or antigen binding domain thereof includes a heavy chain variable region comprising HCDR1 of SEQ ID NO: 41, HCDR2 of SEQ ID NO: 47, HCDR3 of SEQ ID NO: 72, HFR1 of SEQ ID NO: 128, HFR2 of SEQ ID NO: 129, HFR3 of SEQ ID NO: 130, and HFR4 of SEQ ID NO: 131. In some embodiments, the humanized antibody, fragment thereof or antigen binding domain thereof comprises from N-terminus to C-terminus: HFR1 of SEQ ID NO: 128, HCDR1 of SEQ ID NO: 41, HFR2 of SEQ ID NO: 129, HCDR2 of SEQ ID NO: 47, HFR3 of SEQ ID NO: 130, HCDR3 of SEQ ID NO: 72, and HFR4 of SEQ ID NO: 131. In some embodiments of the ADC, the humanized antibody, fragment thereof, or antigen binding domain thereof comprises an amino acid sequence of any one of SEQ ID NOS: 110- 128, as shown in Table 5. In some embodiments of the ADC, the humanized antibody, fragment thereof, or antigen-binding domain thereof comprises an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to any one of SEQ ID NOS: 110-128. In some embodiments of ADCs and Fc fusion proteins, the 30 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO humanized antibody, fragment thereof, or antigen binding domain includes an Fc domain and comprises an amino acid sequence of any one of SEQ ID NOS: 132-150, as shown in Table 6. In some embodiments of the ADC, the humanized antibody, fragment thereof, or antigen- binding domain thereof includes an Fc domain and comprises an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to any one of SEQ ID NOS: 133-151. More detailed descriptions and exemplary embodiments of anti- CDH17 humanized antibodies, fragments thereof, or antigen binding domains thereof are provided in the disclosure below. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 133. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 134. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 135. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 136. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 137. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 138. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 139. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 140. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 141. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 142. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 143. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 144. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 145. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 146. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 147. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 148. In some embodiments, the CDH17 targeting ADC 31 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 149. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 150. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence of SEQ ID NO: 151. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 133. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 134. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 135. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 136. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 137. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 138. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 139. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 32 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 140. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 141. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 142. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 143. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 144. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 145. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 146. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 147. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 148. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 149. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at 33 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 150. In some embodiments, the CDH17 targeting ADC comprises two monomers each comprising an amino acid sequence having at least about 90% (e.g., about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more) sequence identity to SEQ ID NO: 151. In some embodiments, the ADCs include an anti-CDH17 antibody or antigen-binding domain thereof covalently attached to a drug payload by way of a conjugation linker. In other words, an ADC includes one or more (e.g., 1, 2, 3, 4, 5, 6, 7, or 8) linker-payload constructs (e.g., conjugates). In some embodiments, any of the linker-payload constructs described herein can be a branched linker-payload construct. Branched linker-payload constructs can be applied to a CDH17 antibody to form a drug-antibody ratio of 4 (DAR4) ADC by attaching two conjugation linkers to an antibody or antigen-binding domain thereof. In some embodiments, a linker of a CDH17 ADC includes one or more spacer moieties. In some embodiments, the linker includes a highly polar sulfamide spacer. In some instances, a spacer moiety includes a polyethyleneglycol (PEG) moiety. In some embodiments, a spacer moiety includes a polyethyleneglycol (PEG) moiety and a polar acyl or carbamoyl sulfamide moiety. In some embodiments, the ADC is generated by site-specific conjugation of a payload based on glycan remodeling of an IgG domain followed by azide-cyclooctyne click chemistry. Glycoforms of the IgG domain are enzymatically remodeled by endoglycosidase- mediated trimming, followed by glycosyltransferase-mediated transfer of azido-sugar onto the core GlcNAc liberated by endoglycosidase. Then, the azido-remodeled IgG is subjected to an immune cell-engaging polypeptide, which has been modified with a single cyclooctyne for metal-free click chemistry (SPAAC). In some cases, the cyclooctyne-antibody construct contains a spacer between the cyclooctyne and the IgG domain. In some embodiments, the ADC is generated by site-specific conjugation of a payload based on glycan remodeling of an IgG domain followed by thiol alkylation chemistry. Glycoforms of the IgG domain are enzymatically remodeled by endoglycosidase-mediated trimming, followed by glycosyltransferase-mediated transfer of a thiol-modified (and 34 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO disulfide-protected) sugar derivative onto the core GlcNAc liberated by endoglycosidase. Then, the remodeled IgG is subjected to reduction (to convert the disulfide into thiol), potentially followed by oxidation, then reaction with a payload modified with a suitable thiol- reactive reagent. Detailed descriptions of conjugation linker-payload technology and methods for enzymatic glycan remodeling and metal-free click chemistry conjugation for generating ADCs can be found in, e.g., van Geel et al., Bioconj Chem, 26, 2233-2242 (2015), Verkade et al., Antibodies, 7, 12 (2018), Wijdeven et al., MAbs, 14(1), 2078466, (2022), WO 2011 / 136645, WO 2014 / 065661, WO 2016 / 053107, WO 2016 / 170186, WO 2017 / 137456, WO 2017 / 137459, WO 2021 / 015622, WO 2022 / 049211, and US 11,547,763, the disclosures are hereby incorporated by reference in their entirety. Other methods for conjugating linker- payload constructs to form ADCs can be used and are described in, for example, van Berkel SS and van Delft FL, Drug Discov Today Technol., 2018 Dec:30:3-10. A. Drug Payload In some embodiments of the ADC, an anti-CDH17 antibody or antigen-binding domain thereof is conjugated to a drug moiety or a drug payload. Exemplary drug moieties include, but are not limited to, an cytotoxic agent, non-cytotoxic agent, anti-inflammatory agent, or other therapeutic agent (also referred to as a payload or warhead). In some embodiments, a cytotoxic payload or warhead includes a microtubule-disrupting agent or a DNA-damaging agent. Non-limiting examples of microtubule-disrupting agents include auristatin and derivatives thereof, such as monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF), maytansinoids and derivatives thereof such as maytansine, maytansine derivative DM1, and maytansine derivative DM4, and taxoids and derivatives thereof such as paclitaxel and docetaxel. Non-limiting examples of DNA- damaging agents include calicheamicins, duocarmycins, doxorubicin, daunorubicin, CC-1065 analogs, and derivatives thereof. In some embodiments, cytotoxic agents include pyrrolobenzodiazepines, RNA polymerase inhibitors, transcription inhibitors, amatoxins, spliceostatin C, and thailanstatin A. In some embodiments, cytotoxic agents for cancer or non-cancer indications include, but are not limited to, toxin targeting ribosomes, toxin targeting elongation factors, toxins targeting tubulin (e.g., tubulin inhibitors), tubulin depolymerization agents, cytotoxic tubulin inhibitors, microtubule-disrupting agents, topoisomerase I inhibitors, topoisomerase II inhibitors, DNA double strand break inducing 35 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO agents, DNA intercalators, toxins targeting DNA, DNA alkylating molecules, toxins targeting RNA, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, benzodiazepine, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracyl (5-FU), mitoxantrone, an indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin, amanitin, a-amanitin, spliceostatin, thailanstatin, ozogamicin, Amberstatin269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), Monomethyl Auristatin D (MMAD), monomethyl dolastatin 10, Monomethyl Auristatin F (MMAF, mafodotin), N- methylvaline-valine-dolaisoleuine-dolaproine-phenylalanine, Monomethyl Auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleuine-dolaproine-norephedrine, deruxtecan, tesirine, mertansine, ravtansine, leptomycin, duocarmycin, calicheamicin, N- acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, anthracyclines, camptothecins, irinoticans, taxanes, hedgehog inhibitors, nitrogen mustards, histone deacetylase inhibitors, PE38, SN38, irinotecan derivatives, tubulysin, exatecan, duocarmazine, STING agonist, TLR agonist, alpha-Amanitin, SGD-1882, CC-1065, CC- 1065 analogs, 5-benzoylvaleric acid-AE ester (AEVB), colchicine, vinca alkaloids, and any derivative thereof. Drug moieties or payloads useful as a cancer therapy include, but are not limited to, cytotoxic drugs, a proteins or polypeptides possessing a desired biological activity, such as a toxin, e.g., abrin, ricin A, pseudomonas exotoxin, and diphtheria toxin, other suitable proteins such as tumor necrosis factor, α-interferon, β-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator, lymphokines, interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), and other growth factors, a V-ATPase inhibitor, a HSP90 inhibitor, an IAP inhibitor, an mTor inhibitor, a microtubule stabilizer, a microtubule destabilizer, an auristatin, a dolastatin, a maytansinoid, a MetAP (methionine aminopeptidase) , an inhibitor of nuclear export of proteins CRM1, a DPPIV inhibitor, an inhibitor of phosphoryl transfer reactions in mitochondria, a protein synthesis inhibitor, a kinase inhibitor, a CDK2 inhibitor, a CDK9 inhibitor, a proteasome inhibitor, a kinesin inhibitor, an HDAC inhibitor, DNA damaging agents such as alicheamicins, duocarmycins, SN-38, and pyrrolo [2, 1-c] [1, 4] benzodi-azepines (PBDs), a DNA alkylating agent, a DNA 36 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO intercalator, a DNA minor groove binder, a DHFR inhibitor, microtubule disrupting drugs such as auristatin, e.g., monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and auristatin F (AF), other microtubule disrupting drugs such as maytansinoids, e.g., DM1, DM3, and DM4, amanitins, anthracyclines, baccatins, camptothecins, cemadotins, colchicines, colcimids, combretastatins, cryptophycins, discodermolides, docetaxel, doxorubicin, echinomycins, eleutherobins, epothilones, estramustines, lexitropsins, maytansines, methotrexate, netropsins, puromycins, rhizoxins, taxanes, tubulysins, vinca alkaloids, topoisomerase I inhibitors such as camptothecin and derivatives thereof such as, but not limited to, irinotecan, topotecan, lurtotecan, silatecan, etirinotecan pegol, TAS 103, 9- aminocamptothecin, 7-ethylcamptothecin, 10-hydroxycamptothecin, 9-nitrocamptothecin, 10,11-methylenedioxycamptothecin, 9-amino-10, 11-methylenedioxycamptothecin, 9-chloro- 10,11-methylenedioxycamptothecin, 7-(4-methylpiperazinomethylene)-10,11-ethylenedioxy- 20 (S)-camptothecin, 7-(4-methylpiperazinomethylene)-10,11-methylenedioxy-20(S)- camptothecin, 7-(2-(N-isopropylamino)ethyl)-(20S)-camptothecin, and stereoisomers, salts and esters thereof, topoisomerase I / II inhibitors, In some embodiments, an anti-inflammatory therapeutic agent includes synthetic glucocorticoid, glucocorticoid analog, fluticasone furoate (FF), fluticasone propionate (FP), halobetasol propionate, clobetasol propionate, glucocorticoid receptor modulator (GRM), and any derivatives thereof. Non-limiting examples of anti-inflammatory therapeutic agents include glucocorticoid receptor modulators, glucocorticoid receptor agonists, glucocorticoid, cortisol, cortisone acetate, beclometasone, prednisone, prednisolone, methylprednisolone, hydrocortisone, betamethasone, trimcinolone, budesonide, dexamethasone, fluticasone, fluticasone propionate, mometasone, PDE4 inhibitors, GSK256066, anti-inflammatory peptides, anti-inflammatory cytokines, Toll-like receptor (TLR) agonists, TLR7 agonists, TLR8 agonists, TLR9 agonists, TLR7 / 8 dual agonists, interferon gene stimulators (STING) agonists, non-steroidal inflammatory drugs, steroidal inflammatory drugs, and other anti- inflammatory drugs. In some embodiments of any of the anti-CDH17 ADCs described herein, the therapeutic agent can be the drug payload of ABBV-154, ABBV-3373, XMT-2056, and XMT-1660. Descriptions of anti-cancer therapeutic agents, anti-inflammatory therapeutic agents and drug-linker conjugates for ADCs can be found in, for example, WO2017062271A2, 37 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO WO2019106608A1, WO2021046426A1, WO2021016204A1, WO2021216572A1, WO2021178818A2, WO2023102875A1, WO2023217133A1, WO2024240227A1, US20250223375A1, Pal et a., Pharmaceutics, 2023, 15:1807, Wang et al., Acta Pharm Sin B., 2023 Jun 30, 1310):4025-4059, and Huang et al., Pharmacol Rev, 2024 July, 76:579-598, Dixit et al., Arthritis Res Ther, 2024, 26: 216, and Wang et al., J Hematol Oncol, 2025, 18:51, the contents of which are hereby incorporated by reference in their entireties. B. Conjugation Linkers Provided herein are antibody-drug conjugates comprising an anti-CDH17 antibody or antigen-binding domain thereof conjugated to a therapeutic agent, e.g., cytotoxic agent, non- cytotoxic agent, anti-inflammatory agent, and other therapeutic agent by a conjugation linker (e.g., a linker). In other words, an antibody-drug conjugate contains a linker that is conjugated to an agent and to an antibody. In some embodiments, a linker can maintain the ADC in an inactive or nontoxic state when the linker is bound to the antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof can be directly linked to the therapeutic agent via a covalent bond, or the antibody or antigen-binding domain can be linked to the agent indirectly via a linker. A conjugation linker can include one or more (e.g., 1, 2, 3, 4, 5, or more) spacer moieties. In some embodiments, the spacer moieties are connected to produce 2, 3, 4, 5, or more consecutive spacer moieties. Non-limiting spacer moieties include short PEG spacers (e.g., less than 12 PEG units in length), long PEG spacers (e.g., 12 PEG units or more in length), short and polar spacers, hydrophilic spacers, and hydrophilic self-immolative linkers. Exemplary spacers and linkers are described below and in US 9,636,421, US 10,792,369 and US 11,850,286. A conjugation linker can include one or more attachment groups. In some embodiments, an attachment group provides covalent attachment of a linker to an antibody or antigen-binding domain thereof. In some embodiments, an attachment group provides covalent attachment of a linker to a cytotoxic agent. In some embodiments, the attachment group comprises maleimide, caproic acid, or both maleimide and caproic acid. Selection of an attachment group can be based on the selected linker and the attachment site of the antibody or antigen-binding domain thereof, or the selected linker and the selected cytotoxic agent. 38 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, the linker is cleavable or non-cleavable. A cleavable linker can include a cleavable moiety. A non-cleavable linker can include a non-cleavable moiety. In some embodiments, a cleavable linker is a chemically cleavable or enzymatically cleavable linker. In many instances, a cleavable linker is cleaved by environmental differences such as redox potential and pH, and specific lysosomal enzymes in extracellular and intracellular environments. In some embodiments, the cleavable linker is cleavable under certain pH condition (pH sensitive linker), cleavable by a protease (protease sensitive linker), or cleavable in the presence of glutathione (glutathione sensitive linker). Linkers can be acid- sensitive or acid-labile. In some embodiments, a linker is protease cleavable. Alternatively, linkers can be lysosomal protease-sensitive. In some embodiments, a chemically cleavable linker is pH-sensitive or reduction sensitive. In some embodiments, an enzymatically cleavable linker is a peptide based linker, a β-glucuronide based linker, or a phosphate based linker. In some embodiments, a cleavable linker is a cleavable disulfide. In some embodiments, the linker includes vc-PABC, vc-PABC-DMEDC, and a disulfide-containing cleavable linker sulfo-SPDB. In some embodiments, a β-glucuronide based linker is a β- glucuronidase sensitive linker or a β-galactosidase sensitive linker. In some embodiments, a linker is a glutathione-sensitive disulfide linker. In some embodiments, a non-cleavable linker is a thioether linker or a maleimidocaproyl (mc) linker. In some instances, a non-cleavable linker is a nonreducible thioether linkage. In some embodiments, a non-cleavable linker is N-succinimidyl-4- (maleimidomethyl) cyclohexane-1-carboxylate (SMCC) or linear alkyl / alkoxy. In some embodiments, the linker is a tetrapeptide linker such as, but not limited to, glycine-glycine-phenylalanine-glycine (GGFG) or a maleimide-cysteine (mc)-valine- citrulline-para-aminobenzyloxycarbonyl (mc-vc-PABC) linker. In some instances, the linker is 4-(4-acetylphenoxy) butanoic acid, mc-GGFG-aminomethoxy, mc-PEG-carbonate, and the like. In some embodiments, a conjugation linker comprises hydrazone, (4-(4′- acetylphenoxy)butanoic acid) hydrazone, (6-maleimidocaproyl) hydrazone, acyl hydrazone disulfide (AcButDMH), N-ε-maleimidocaproic acid hydrazide (EMCH), N-Succinimidyl 4- (2-pyridyldithio)butyrate (SPDB), sulfo-SPDB, succinimidyl 3-(2-pyridyldithio)propionate (SPDP), 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU), pyrimidine-CL2 A-carbonate, valine-alanine, valine-citrulline 39 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO (Val-Cit), phenylalanine-lysine (Phe-Lys), valine-alanine, Val-Cit-para-aminobenzyl carbamate (PABC)(Val-Cit-PABC), Val–Cit-p-aminobenzyl (PAB)(Val-Cit-PAB), maleimidohexanoic, maleimidohexanoic-Val-Cit-PABC, 2-aminobenzamidoxime, mercaptoethylpyrazolone, CL2A (PEG8- and triazole-containing PABC-peptide-mc linker), glutamic acid-valine-citrulline (EVCit), EVCit-PABC, Val-Ala-PABC, Glu-Val-Cit-PABC, Ala-Ala-Asn-PABC, Gly-Val-Cit-PABC, Gly-Gly-Gly-PABC, Gly-Gly-Phe-Gly-PABC, Val-Cit-PAB, Val-Ala-PAB, Glu-Val-Cit-PAB, Ala-Ala-Asn-PAB, Gly-Val-Cit-PAB, Gly- Gly-Gly-PAB, Gly-Gly-Phe-Gly-PAB, mc-Val-Cit-PABC, mc-Gly-Gly-Phe-Gly, mc-PEG2- Val-Cit-PABA-Cyc, PEG2-Val-Cit-PABA, hydroxylamine-PEG4, and derivatives thereof. In some embodiments, a conjugation linker comprises an asparagine-containing legumain cleavable linker such as those described in WO2025042953, Miller et al., Bioconjugate Chem.2021, 32, 4, 842–858, Gray et al., Xenobiotica, 2024 Aug, 54(8):458- 468, the disclosures including figures and chemical structures are hereby incorporated by reference. Useful linkers and methods for conjugating linkers to antibodies and payloads are described in van Delft, Floris, and John M. Lambert, eds. Chemical Linkers in Antibody-Drug Conjugates (ADCs), Vol.81. Royal Society of Chemistry, 2021, and Wang et al., J Hematol Oncol, 2025, 18:51. Glycan remodeling with endoglycosidase and GalNAc-transferase in the presence of 6-azidoGalNAc followed by metal-free click chemistry ligation of one or more linker- payloads can be used to generate CDH17-targeted ADC molecules. A linker of a linker-payload construct can include sulfamide and polyethyleneglycol (PEG) moieties. The linker can contain an acryl sulfamide or a carbamoyl sulfamide. A linker can include a protease-sensitive cleavable moiety. A linker can be a branched linker. The branched linker can include two protease-sensitive cleavable moieties. In some embodiments, a branched linker contains two Val-Cit-p-aminobenzylooxycarbonyl (vc- PABC) moieties. In some embodiments, a linker includes attachment groups, which can be electrophilic in nature and include: maleimide groups, activated disulfides, active esters such as NHS esters and HOBt esters, haloformates, acid halides, alkyl and benzyl halides such as haloacetamides. 40 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments of an ADC, the linker comprises one or more spacer moieties. In some embodiments, the spacer moieties comprise para-aminobenzyl carbamate (PABC), cyclodextrin, polymers, PEG or PEG8. Detailed descriptions of useful conjugation linkers and spacers can be found in, for example, US 9,636,421 and US 10,792,369, the contents of which are hereby incorporated by reference in their entirety. In some embodiments, the linker comprises a functional group that forms a covalent bond at an conjugation site of the antibody or antigen-binding domain. Exemplary functional groups include, but are not limited to, a maleimide group, an iodoacetamide group, a vinyl sulfone group, an acrylate group, an acrylamide group, an acrylonitrile group, or a methacrylate group. In some embodiments of an ADC, the anti-CDH17 antibody or antigen-binding domain thereof is conjugated to a linker-payload construct at a conjugation site. In some embodiments, the conjugation site is an asparagine, cytosine, or lysine of an antibody or an antigen-binding domain thereof. In some embodiments, the conjugation site is a conserved N- glycosylation site on an Fc domain of an antibody, such as an asparagine located in the region of positions 290 to 305 of the Fc domain, generally at asparagine at position 297. Any conjugation method known to one skilled in the art can be used to chemically conjugate a linker-payload conjugate to an antibody or antigen-binding domain thereof at a pre- determined site such that the ADC is stable during production and in circulation upon administration to a subject. Site-specific conjugation methods can utilize engineered cysteines, unnatural amino acids, selenocysteine residues, enzymatic conjugation through glucotransferase and transglutaminases, and other techniques. In some embodiments, a linker-payload construct is attached to an antibody at the conjugation site according to methods utilizing enzymatic trimming of the antibody glycan to the N-acetylglucosamine moiety attached directly to an asparagine (e.g., N297) in the CH2 domain of the antibody prior to linker-payload conjugate attachment. Such methods include introducing an azidosugar onto the antibody core GlcNAc (N-acetyl-D-glucosamine) by trimming and glycosyl transfer in a one-pot process, and then metal-free click conjugation of a linker-payload conjugate where the attachment of the linker-payload conjugate. In some embodiments, the linker-payload conjugate is a BCN-linker-payload construct. A BCN- linker-payload construct is prepared from bicyclo(6.1.0)non-4-yne (BCN) alcohol via addition of chlorosulfonyl isocyanate (CSI) and an amine of a linker-payload construct. 41 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Detailed descriptions of methods for synthesizing BCN-linker-payload constructs and methods for enzymatic trimming and conjugation reactions can be found in Verkade et al., Antibodies, 2018, 7, 12 and Lyon et al., Nat Biotechnol, 2014, 32, 1059-1062, the contents are hereby incorporated by reference in their entireties including the supplementary materials. In some instances, an antibody undergoes trimming with endoglycosidase and enzymatic transfer of GalNAz under the action of the galactosyl transferase GalT(Y289L) variant, followed by copper-free click conjugation of a linker-payload conjugate to produce an ADC. In some embodiments, the enzymatic transfer step includes transfer of a 6-azidoGalNAc substrate under the action of β-(1,4)-N-acetylgalactosaminyl transferase, followed by metal- free click conjugation of a linker-payload conjugate to produce an ADC. Such methods are described in Verkade et al., Antibodies, 2018, 7(1):12, van Geel et al., Bioconjugate Chem, 2015, 26:2233-42, and Zeglis et al., Bioconjugate Chem, 2013, 24:1057-67. In other embodiments, ADCs described herein include cysteine-engineered antibodies wherein one or more amino acids of a wild-type or parent antibody are replaced with a cysteine amino acid antibody. In some instances, any one or more of the following residues may be substituted with cysteine: V205 (Kabat numbering) of the light chain; A118 (EU numbering) of the heavy chain; and S400 (EU numbering) of the heavy chain Fc region, and S121, and K149 of the light chain. The term "ADC composition", as used herein, refers to a composition containing heterogeneous mixture of antibody species containing various drug loads ("DL"). The average drug-to-antibody ratio (DAR) of the entire heterogenous ADC composition is referred to herein as "average DAR" or "DAR". For example, an ADC composition comprises of mixture of antibody species, each with their own DL (some species in the mixture are DL2, some species in the mixture are DL4, some species in the mixture are DL6, and some species in the mixture are DL8), and the average DAR for the entire composition may be about 4. In some embodiments, the term "percent DL" may be used to describe the percent of a specific DL species within the heterogenous ADC composition (e.g., percent DL2 is 5 about 10% to about 30% of the total heterogenous ADC composition). In some embodiments, drugs or a cytotoxic agent may be conjugated to antibodies or an antigen- binding domain thereof via sulfhydryl groups. The sulfhydryl groups can be sulfhydryl groups on cysteine side chains. The cysteine residues can be naturally present in an antibody (e.g., interchain disulfides) or introduced by other means, e.g., mutagenesis. 42 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO For example, DL0 has no drug load on the antibody. For example, DL2 has a drug load of two. For example, DAR4 has a drug antibody ratio of 4. In some embodiments, an antibody or antigen-binding domain thereof disclosed herein has a drug antibody ratio of 2. In some embodiments, an antibody or antigen-binding domain thereof disclosed herein has a drug antibody ratio of 4. In some embodiments, an antibody or antigen-binding domain thereof disclosed herein has a drug antibody ratio of about 1–10. In some embodiments, the antibody or antigen-binding domain thereof has a drug antibody ratio of about 1. In some embodiments, the antibody or antigen-binding domain thereof has a drug antibody ratio of about 2. In some embodiments, the antibody or antigen-binding domain thereof has a drug antibody ratio of about 3. In some embodiments, the antibody or antigen-binding domain thereof has a drug antibody ratio of about 4. In some embodiments, the antibody or antigen- binding domain thereof has a drug antibody ratio of about 5. In some embodiments, the antibody or antigen-binding domain thereof has a drug antibody ratio of about 6. In some embodiments, the antibody or antigen-binding domain thereof has a drug antibody ratio of about 7. In some embodiments, the antibody or antigen-binding domain thereof has a drug antibody ratio of about 8. In some embodiments, the antibody or antigen-binding domain thereof has a drug antibody ratio of about 9. In some embodiments, the antibody or antigen- binding domain thereof has a drug antibody ratio of about 10. Various methods exist, and are known to those skilled in the art, for calculating the percent DL species and / or average DAR in an ADC composition. For example, hydrophobic interaction chromatography (HIC) which separates DL species based on the number of drugs loaded. LC-MS assays have also been developed to assess DL distribution. Exemplary methods for calculating the drug load distribution in an ADC composition can be found, for example, in Journal of Chromatography B, 1060, (2017), 182-189. For example, DL2 has a drug load of two. In one embodiment, the conjugation sites for DL2 comprise HC 224. For example, DL4 has a drug load of four. In one embodiment, the conjugation sites for DL4a comprise HC 224. In one embodiment, the conjugation sites for DL4b comprise HC 233. For example, DL6 has a drug load of six. In one embodiment, the conjugation sites for DL6 comprise HC 224 and HC 233. For example, DL8 has a drug load of eight. In one embodiment, the conjugation sites for DL8 comprise HC 224 and HC 233. 43 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO C. Anti-CDH17 Antibodies and Antigen-Binding Domains Provided herein are antibodies, fragments thereof, and antigen-binding domains that specifically bind cadherin 17, such as the extracellular domain of CDH17. In some embodiments, the antibodies, fragments thereof and antigen-binding domains bind human CDH17, and in particular, the extracellular domain of human CDH17. In some embodiments, provided herein are humanized or de-immunized antibodies, fragments thereof, and antigen-binding domains comprising a heavy chain variable region comprising HCDR1 of SEQ ID NO: 41, HCDR2 of any one of SEQ ID NOS: 42-60, and HCDR3 of any one of SEQ ID NOS: 61-78. In some embodiments, the humanized or de- immunized antibodies, fragments thereof, and antigen-binding domains comprise a heavy chain variable region comprising HCDR1 of SEQ ID NO: 41, HCDR2 of SEQ ID NO: 47, and HCDR3 of SEQ ID NO: 72. In some embodiments, the humanized or de-immunized antibodies, fragments thereof, and antigen-binding domains comprise a heavy chain variable region comprising HCDR1 of SEQ ID NO: 41, HCDR2 of SEQ ID NO: 47, HCDR3 of SEQ ID NO: 72, HFR1 of SEQ ID NO: 128, HFR2 of SEQ ID NO: 129, HFR3 of SEQ ID NO: 130, and HFR4 of SEQ ID NO: 131. In some embodiments, the humanized or de-immunized antibodies, fragments thereof, and antigen-binding domains comprise an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to SEQ ID NO: 109. In some embodiments, the humanized or de-immunized antibodies, fragments thereof, and antigen- binding domains comprise an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to SEQ ID NO: 109, and can bind to human CDH17. In some embodiments, the humanized or de-immunized antibodies, fragments thereof, and antigen- binding domains comprise an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to SEQ ID NO: 109, and have substantially equivalent binding activity or specificity as an antibody, fragment thereof, or antigen binding domain of SEQ ID NO: 109. In some embodiments, the humanized or de-immunized antibodies, fragments thereof, and antigen-binding domains comprise an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to SEQ ID NO: 109 and a heavy chain variable region 44 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO comprising HCDR1 of SEQ ID NO: 41, HCDR2 of SEQ ID NO: 47, and HCDR3 of SEQ ID NO: 72. In some embodiments, the humanized or de-immunized antibodies, fragments thereof, and antigen-binding domains comprise an amino acid sequence of SEQ ID NO: 109 and one or more amino acid modifications in one or more of the framework regions of the heavy chain variable region. In other embodiments, the humanized or de-immunized antibodies, fragments thereof, and antigen-binding domains comprise an amino acid sequence of SEQ ID NO: 109 and one or more amino acid modifications in one or more of the CDRs and / or one or more of the FRS of the heavy chain variable region. i. Modifications in CDRs The anti-CDH17 antibody or antigen-binding domain thereof may have at least one or more amino acid modifications in various regions of the antibody. The anti-CDH17 antibody or antigen-binding domain thereof may be modified by at least one or more amino acid substitution, deletion, addition, or a combination thereof at one or more position while the variant CDH17 binding protein substantially retains the biological characteristics of the unmodified protein, such as binding to CDH17. In some embodiments, the amino acid sequence of the CDH17 antibody or antigen-binding domain thereof may have at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 amino acid insertions, deletions, substitutions or a combination thereof. In some instances, one or more amino acid modifications described herein can be in the antigen-binding (Fab) fragments of an antibody or antibody binding domain thereof. In some instances, the modification can be within the Fab region of a heavy chain polypeptide (H) and a first light chain polypeptide (L). In some embodiments, the modification can be within a heavy chain variable domain (VH), a heavy chain constant domain (CH1), a light chain variable domain (VL), a light chain constant domain (CL), or a combination thereof. In some embodiments, one or more amino acid modification can be in the Fab VH and VL with the N-terminal region. The VH, VL, HC or LC sequence disclosed herein may be a variant sequence with up to 15 amino acid substitutions, insertion, or deletions. For example, the variant sequence may have up to 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid substitution(s), addition(s), or deletion(s). The sequence variation may exclude one or more 45 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO or all of the CDRs, for example, the CDRs are the same as the VH, VL, HC or LC sequence and the variation is in the remaining portion of the VH or VL, HC, or LC sequence, so that the CDR sequences are fixed and intact. Each of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 may be modified alone or in combination with any other CDR, in any permutation or combination. Typically, the modification is a substitution, particularly a conserved substitution, for example in Table 2 below. Table 2 Side Chain Members Hydrophobic Met, Ala, Val, Leu Ile g In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises CDRs: HCDR1 selected from the group consisting of SEQ ID NO: 41, HCDR2 selected from the group consisting of SEQ ID NOs: 42-60, and HCDR3 selected from the group consisting of SEQ ID NOs: 61-78, functional fragments thereof, functional variants thereof, and combination thereof. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises CDRs: HCDR1 of SEQ ID NO: 41, HCDR2 of SEQ ID NOs: 43, and / or HCDR3 of SEQ ID NO: 62, functional fragments thereof, functional variants thereof, and combination thereof. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises CDRs: HCDR1 of SEQ ID NO: 41, HCDR2 of SEQ ID NOs: 44, and / or HCDR3 of SEQ ID NO: 63, functional fragments thereof, functional variants thereof, and combination thereof. In some embodiments, the anti-CDH17 antibody or an antigen- binding domain thereof comprises CDRs: HCDR1 of SEQ ID NO: 41, HCDR2 of SEQ ID NOs: 43, and / or HCDR3 of SEQ ID NO: 64, functional fragments thereof, functional variants thereof, and combination thereof. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises CDRs: HCDR1 of SEQ ID NO: 41, HCDR2 of SEQ ID NOs: 45, and / or HCDR3 of SEQ ID NO: 65, functional fragments thereof, functional 46 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO variants thereof, and combination thereof. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises CDRs: HCDR1 of SEQ ID NO: 41, HCDR2 of SEQ ID NOs: 46, and / or HCDR3 of SEQ ID NO: 65, functional fragments thereof, functional variants thereof, and combination thereof. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises CDRs: HCDR1 of SEQ ID NO: 41, HCDR2 of SEQ ID NOs: 47, and / or HCDR3 of SEQ ID NO: 72, functional fragments thereof, functional variants thereof, and combination thereof. In some embodiments, each domain of three complementarity-determining region LCDR: LCDR1, LCDR2, and LCDR3 for VL, and HCDR1, HCDR2, and HCDR3 for VH may be modified alone or in combination with any other CDR, in any permutation or combination. In some embodiments, the LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 may be modified by substitution, deletion or insertion of 1 amino acid to 10 amino acids. In some embodiments, the LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 may have 1 amino acid to 2 amino acids, 1 amino acid to 3 amino acids, 1 amino acid to 4 amino acids, 1 amino acid to 5 amino acids, 1 amino acid to 6 amino acids, 1 amino acid to 7 amino acids, 1 amino acid to 8 amino acids, 1 amino acid to 9 amino acids, 1 amino acid to 10 amino acids, 2 amino acids to 3 amino acids, 2 amino acids to 4 amino acids, 2 amino acids to 5 amino acids, 2 amino acids to 6 amino acids, 2 amino acids to 7 amino acids, 2 amino acids to 8 amino acids, 2 amino acids to 9 amino acids, 2 amino acids to 10 amino acids, 3 amino acids to 4 amino acids, 3 amino to 5 amino acids, 3 amino acids to 6 amino acids, 3 amino acids to 7 amino acids, 3 amino acids to 8 amino acids, 3 amino acids to 9 amino acids, 3 amino acids to 10 amino acids, 4 amino acids to 5 amino acids, 4 amino acids to 6 amino acids, 4 amino acids to 7 amino acids, 4 amino acids to 8 amino acids, 4 amino acids to 9 amino acids, 4 amino acids to 10 amino acids, 5 amino acids to 6 amino acids, 5 amino acids to 7 amino acids, 5 amino acids to 8 amino acids, 5 amino acids to 9 amino acids, 5 amino acids to 10 amino acids, 6 amino acids to 7 amino acids, 6 amino acids to 8 amino acids, 6 amino acids to 9 amino acids, 6 amino acids to 10 amino acids, 7 amino acids to 8 amino acids, 7 amino acids to 9 amino acids, 7 amino acids to 10 amino acids, 8 amino acids to 9 amino acids, 8 amino acids to 10 amino acids, or 9 amino acids to 10 amino acids modifications. In some embodiments, the LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 may have 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, or 10 amino acids modifications. 47 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, the LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 may have at least 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, or 9 amino acids modifications. In some embodiments, the LCDR-1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 may have at most 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, or 10 amino acids modifications. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises HCDR1 selected from the group consisting of SEQ ID NO: 41 or a variant HCDR1 thereof. In some embodiments, the HCDR1 may include a sequence that is at least 60% identical (e.g., at least 62%, at least 64%, at least 66%, at least 68%, at least 70%, at least 72%, at least 74%, at least 76%, at least 78%, at least 80%, at least 82%, at least 84%, at least 85%, at least 86%, at least 88%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 41. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises HCDR2 selected from the group consisting of SEQ ID NOs: 43-60 or a variant HCDR2 thereof. In some embodiments, the polypeptide comprises a HCDR2 having the amino acid sequence set out in any one of SEQ ID NOs: 42-60. In some embodiments, the HCDR2 includes a sequence that is at least 60% identical (e.g., at least 62%, at least 64%, at least 66%, at least 68%, at least 70%, at least 72%, at least 74%, at least 76%, at least 78%, at least 80%, at least 82%, at least 84%, at least 85%, at least 86%, at least 88%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to any one of SEQ ID NOs: 42-60. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises HCDR3 selected from the group consisting of SEQ ID NOs: 61-75 or a variant HCDR3 thereof. In some embodiments, the polypeptide comprises a HCDR3 having the amino acid sequence set out in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof may include a sequence that is at least 60% identical (e.g., at least 62%, at least 64%, at least 66%, at least 68%, at least 70%, at least 72%, at least 74%, at least 76%, at least 78%, at least 80%, at least 82%, at least 84%, at least 85%, at least 86%, at least 88%, at least 90%, at least 91%, at least 92%, at least 93%, 48 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to any one of SEQ ID NOs: 61-75. Exemplary anti-CDH17 antibodies or antigen-binding domain thereof sequences are listed in Table 3 below. Table 3 Construct Description SEQ ID Sequence NO: G T A G T A G T A G T A 49 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO CDH17_v Full Length5QVQLQESGGGLVQPGGSTRLSCVSSRTFSYYDMG hh_0946 Sequence WFRQAPGKEREFVALLSWRGNNAEYSDFVMGRFT A G T A G V A G T A G T A G T A 50 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO HCDR1 41YDMGHCDR2 43LLSWRGNNAEYSDDVMGG T A G V A G T A G V A G T A 51 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO HCDR3 68TYGGARSVRLCDH17 v Full Length16QVQLQESGGGLVQPGGSTRLSCVSSRTFSYYDMG V A G V A G V A G T A G T A G T 52 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO VSRGNTQNSVNLQMNNLKPEDTGIYYCAVTYGGA RSVRLWGQGTQVTVSS G T A G V A G T A G V A G T A 53 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO HCDR2 43LLSWRGNNAEYSDDVMG HCDR3 77TYGTARSVRSG T A G T A G T A G T A G T A 54 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO CDH17_v Full Length32QVQLQESGGGLVQPGGSTRLSCVSSRTFSYYDMG hh_0689 Sequence WFRQAPGKEREFVALLSWRGNNAEYSDFVMGRFT A G T A G T A G T A G T A G T A 55 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO HCDR1 41YDMGHCDR2 51LLSWRGNNAEYSDTVMG G V A G T A G T A G T A n some emo mens, e an - an oy or an an gen- n ng oman thereof comprises HCDR1 having an amino acid sequence of YDMG (SEQ ID NO: 41). In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLSWRGX2NAEYX3DX4VX5G (SEQ ID NO: 79), wherein: X2 is selected from: E or N; X3 is selected from: S or R; X4 is selected 56 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO from: S, D, or F; and X5is selected from: M or H. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLSWX1GNNAEYX3DX4VX5G (SEQ ID NO: 81), wherein: X1 is selected from: N or R; X3is selected from: S or R; X4is selected from: S, D, or F; and X5is selected from: M or H. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLSWX1GX2NAEYRDX4VX5G (SEQ ID NO: 82), wherein: X1 is selected from: N or R; X2 is selected from: E or N; X4is selected from: S, D, or F; and X5is selected from: M or H. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein: X1 is selected from: N or R; X2 is selected from: E or N; X3 is selected from: S or R; X4 is selected from: D or F; and X5 is selected from: M or H. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLSWX1GX2NAEYX3DX4VHG (SEQ ID NO: 84), wherein: X1 is selected from: N or R; X2 is selected from: E or N; X3 is selected from: S or R; and X4 is selected from: S, D, or F. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLDWX11GX12X13X14EYX15X16X17VX18G (SEQ ID NO: 88), wherein: X11 is selected from: N or R; X12is selected from: E, N, I, or Y; X13is selected from: N or Y; X14is selected from: A or S; X15 is selected from: S, R, or A; X16 is selected from: D or E; X17 is selected from: S, D, F or T; and X18is selected from: M or H. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLX10WRGX12X13X14EYX15X16X17VX18G (SEQ ID NO: 90), wherein: X10is selected from: S or D; X12 is selected from: E, N, I, or Y; X13 is selected from: N or Y; X14 is selected from: A or S; X15is selected from: S, R, or A; X16is selected from: D or E; X17is selected from: S, D, F or T; and X18 is selected from: M or H. In some embodiments, the anti- CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLX10WX11GX12X13X14EYX15X16X17VX18G (SEQ ID NO: 91), wherein: X10 is selected from: S or D; X11 is selected from: N or R; X12 is selected from: N, I, or Y; X13is selected from: N or Y; X14is selected from: A or S; X15is selected from: S, R, or A; X16 is selected from: D or E; X17 is selected from: S, D, F or T; and X18 is selected from: M or H. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of 57 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO LLX10WX11GX12YX14EYX15X16X17VX18G (SEQ ID NO: 92), wherein: X10is selected from: S or D; X11is selected from: N or R; X12is selected from: E, N, I, or Y; X14is selected from: A or S; X15 is selected from: S, R, or A; X16 is selected from: D or E; X17 is selected from: S, D, F or T; and X18is selected from: M or H. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLX10WX11GX12X13SEYX15X16X17VX18G (SEQ ID NO: 93), wherein: X10is selected from: S or D; X11 is selected from: N or R; X12 is selected from: E, N, I, or Y; X13 is selected from: N or Y; X15is selected from: S, R, or A; X16is selected from: D or E; X17is selected from: S, D, F or T; and X18 is selected from: M or H. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLX10WX11GX12X13X14EYX15X16X17VX18G (SEQ ID NO: 94), wherein: X10 is selected from: S or D; X11 is selected from: N or R; X12 is selected from: E, N, I, or Y; X13 is selected from: N or Y; X14 is selected from: A or S; X15 is selected from: R or A; X16 is selected from: D or E; X17 is selected from: S, D, F or T; and X18 is selected from: M or H. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLX10WX11GX12X13X14EYX15EX17VX18G (SEQ ID NO: 95), wherein: X10is selected from: S or D; X11is selected from: N or R; X12is selected from: E, N, I, or Y; X13 is selected from: N or Y; X14 is selected from: A or S; X15 is selected from: S, R, or A; X17is selected from: S, D, F or T; and X18is selected from: M or H. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR2 having an amino acid sequence of LLX10WX11GX12X13X14EYX15X16X17VHG (SEQ ID NO: 97), wherein: X10 is selected from: S or D; X11is selected from: N or R; X12is selected from: E, N, I, or Y; X13is selected from: N or Y; X14 is selected from: A or S; X15 is selected from: S, R, or A; X16 is selected from: D or E; and X17is selected from: S, D, F or T. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR3 having an amino acid sequence of TX6GX7AX8SVRX9 (SEQ ID NO: 80), wherein: X6 is H or Y; X7 is G, T, V, K or N; X8 is R or K; and X9is S or L. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR3 having an amino acid sequence of TYGX7AX8SVRX9 (SEQ ID NO: 85), wherein: X7is G, T, V, K or N; X8is R or K; and X9is S or L. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR3 having an amino acid sequence of TX6GX7AKSVRX9(SEQ ID NO: 86), wherein: X6 is H or Y; X7 is G, T, V, K or N; and X9 is S or L. In some embodiments, the anti-CDH17 58 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO antibody or an antigen-binding domain thereof comprises HCDR3 having an amino acid sequence of TX6GX7AX8SVRL (SEQ ID NO: 87), wherein: X6 is H or Y; X7 is G, T, V, K or N; and X8is R or K. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR3 having an amino acid sequence of TX19GX20AX21SVRX22(SEQ ID NO: 96), wherein: X19 is H or Y; X20 is G, T, V, K, or N; X21 is R or K; and X22 is S, L, K, or A. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR3 having an amino acid sequence of TYGX20AX21SVRX22 (SEQ ID NO: 98), wherein: X20is G, T, V, K, or N; X21is R or K; and X22is S, L, K, or A. In some embodiments, the anti-CDH17 antibody or an antigen-binding domain thereof comprises HCDR3 having an amino acid sequence of TX19GX20AKSVRX22(SEQ ID NO: 99), wherein: X19 is H or Y; X20 is G, T, V, K, or N; and X22 is S, L, K, or A. Exemplary sequences for HCDR2 and HCDR3 are listed in Table 4 below. Table 4 of HCDR1, HCDR2, and HCDR3 regions SEQ ID NO:NameSequence 41 HCDR1 YDMS, , 59 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO HCDR2 LLDWX11GX12X13X14EYX15X16X17VX18G, wherein: X11is N or R; X12is: E, N, I, or Y; X13is N or Y; X14is A X i R A X i D E X i l d s : : , , : , , d , , S, 60 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO HCDR3 TX19GX20AKSVRX22, wherein: X19 is H or Y; X20 is selected from: G, T, V, K, or N; and X22 is selected fS L K A comprises a T67V mutation in an amino acid sequence as set out in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof comprises a Q37Y, A38Y, R52I and / or T67V mutations in an amino acid sequence as set out in SEQ ID NO: 1, wherein the N-terminal amino acid Q is at position 0. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises a heavy chain variable region selected from the group consisting of SEQ ID NOs: 1-40 functional fragments thereof, and functional variants thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises a heavy chain variable region of SEQ ID NO: 1. In some embodiments, the anti- CDH17 antibodies or antigen-binding domain thereof comprises a heavy chain variable region of SEQ ID NO: 2. In some embodiments, the anti-CDH17 antibodies or antigen- binding domain thereof comprises a heavy chain variable region of SEQ ID NO: 3. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises a heavy chain variable region of SEQ ID NO: 4. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises a heavy chain variable region of SEQ ID NO: 5. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises a heavy chain variable region of SEQ ID NO: 6. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises a heavy chain variable region of SEQ ID NO: 109. In some embodiments, a heavy chain variable domain described herein may be modified by at least one amino acid substitution, deletion or insertion, wherein the variant anti-CDH17 antibodies or antigen-binding domain thereof substantially retains the biological characteristics of the unmodified protein, such as binding to CDH17. In some embodiments, a heavy chain variable domain may be modified alone or in combination with any other CDR, in any permutation or combination. In some embodiments, the heavy chain variable domain may be modified by the substitution, deletion or insertion of 1 amino acid to 10 amino acids. In some embodiments, the heavy chain variable domain may have 1 amino acid to 2 amino acids, 1 amino acid to 3 amino acids, 1 amino acid to 4 amino acids, 1 amino acid to 5 amino 61 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO acids, 1 amino acid to 6 amino acids, 1 amino acid to 7 amino acids, 1 amino acid to 8 amino acids, 1 amino acid to 9 amino acids, 1 amino acid to 10 amino acids, 2 amino acids to 3 amino acids, 2 amino acids to 4 amino acids, 2 amino acids to 5 amino acids, 2 amino acids to 6 amino acids, 2 amino acids to 7 amino acids, 2 amino acids to 8 amino acids, 2 amino acids to 9 amino acids, 2 amino acids to 10 amino acids, 3 amino acids to 4 amino acids, 3 amino to 5 amino acids, 3 amino acids to 6 amino acids, 3 amino acids to 7 amino acids, 3 amino acids to 8 amino acids, 3 amino acids to 9 amino acids, 3 amino acids to 10 amino acids, 4 amino acids to 5 amino acids, 4 amino acids to 6 amino acids, 4 amino acids to 7 amino acids, 4 amino acids to 8 amino acids, 4 amino acids to 9 amino acids, 4 amino acids to 10 amino acids, 5 amino acids to 6 amino acids, 5 amino acids to 7 amino acids, 5 amino acids to 8 amino acids, 5 amino acids to 9 amino acids, 5 amino acids to 10 amino acids, 6 amino acids to 7 amino acids, 6 amino acids to 8 amino acids, 6 amino acids to 9 amino acids, 6 amino acids to 10 amino acids, 7 amino acids to 8 amino acids, 7 amino acids to 9 amino acids, 7 amino acids to 10 amino acids, 8 amino acids to 9 amino acids, 8 amino acids to 10 amino acids, or 9 amino acids to 10 amino acids modifications. In some embodiments, HCDR may have 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, or 10 amino acids modifications. In some embodiments, the heavy chain variable domain may have at least 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, or 9 amino acids modification. In some embodiments, the heavy chain variable domain may have at most 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, or 10 amino acids modification. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises a heavy chain variable domain selected from the group consisting of SEQ ID NOs: 1-40 or a variant heavy chain variable domain thereof. In some embodiments, the anti- CDH17 antibody or antigen-binding domain thereof may include a HCDR sequence that is at least 60% identical (e.g., at least 62%, at least 64%, at least 66%, at least 68%, at least 70%, at least 72%, at least 74%, at least 76%, at least 78%, at least 80%, at least 82%, at least 84%, at least 85%, at least 86%, at least 88%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to any one of SEQ ID NOs: 1-40 or 109. 62 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof can comprise SEQ ID NO: 1. The anti-CDH17 antibodies or antigen-binding domain thereof described herein may be modified by at least one amino acid substitution, deletion or insertion, wherein the variant anti-CDH17 antibodies or antigen-binding domain thereof substantially retains the biological characteristics of the unmodified protein, such as binding to CDH17. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof may be modified by the substitution, deletion or insertion of 1 amino acid to 10 amino acids. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof may have 1 amino acid to 2 amino acids, 1 amino acid to 3 amino acids, 1 amino acid to 4 amino acids, 1 amino acid to 5 amino acids, 1 amino acid to 6 amino acids, 1 amino acid to 7 amino acids, 1 amino acid to 8 amino acids, 1 amino acid to 9 amino acids, 1 amino acid to 10 amino acids, 2 amino acids to 3 amino acids, 2 amino acids to 4 amino acids, 2 amino acids to 5 amino acids, 2 amino acids to 6 amino acids, 2 amino acids to 7 amino acids, 2 amino acids to 8 amino acids, 2 amino acids to 9 amino acids, 2 amino acids to 10 amino acids, 3 amino acids to 4 amino acids, 3 amino to 5 amino acids, 3 amino acids to 6 amino acids, 3 amino acids to 7 amino acids, 3 amino acids to 8 amino acids, 3 amino acids to 9 amino acids, 3 amino acids to 10 amino acids, 4 amino acids to 5 amino acids, 4 amino acids to 6 amino acids, 4 amino acids to 7 amino acids, 4 amino acids to 8 amino acids, 4 amino acids to 9 amino acids, 4 amino acids to 10 amino acids, 5 amino acids to 6 amino acids, 5 amino acids to 7 amino acids, 5 amino acids to 8 amino acids, 5 amino acids to 9 amino acids, 5 amino acids to 10 amino acids, 6 amino acids to 7 amino acids, 6 amino acids to 8 amino acids, 6 amino acids to 9 amino acids, 6 amino acids to 10 amino acids, 7 amino acids to 8 amino acids, 7 amino acids to 9 amino acids, 7 amino acids to 10 amino acids, 8 amino acids to 9 amino acids, 8 amino acids to 10 amino acids, or 9 amino acids to 10 amino acids modifications. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof may have 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, or 10 amino acids modifications. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof may have at least 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, or 9 amino acids modification. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof may have at most 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, or 10 amino acids modification. 63 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof as disclosed herein can comprise an amino acid sequence, and the amino acid sequence of the polypeptide may be at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1. For example, the amino acid sequence of the anti-CDH17 antibodies or antigen-binding domain thereof can be between 80% and about 100% identical to the polypeptide sequence of SEQ ID NO: 1. The HCDR1, HCDR2, and HCDR3 can exhibit one of a finite number of main chain conformation (canonicals). The particular canonical structure class of a CDR can be defined by both the length of the CDR and by the loop packing, determined by residues located at key position in both the CDRs and the framework regions. One or more changes in canonical structures by adding, deleting, substituting one or more amino acid within the key position may result in distinct changes in the antibody (e.g., antigen sensitivity or binding affinity). In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof comprises at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten amino acid substitutions at position 25-106 (according to Kabat numbering) in a heavy chain variable domain of SEQ ID NO: 1. In some cases, the substitution of amino acid may be with I, Y, D, R, N, S, A, E, T, F, H, V, L, or K. In some embodiments, the substitution at position at position 25-106 (according to Kabat numbering) in heavy chain variable domain comprises or any combination thereof R25I, Q37Y, A38Y, S50D, N52R, E54N, E54I, N55Y, N55R, A56S, S59R, S59A, D60E, S61D, S61T, S61F, M63H, T67V, H98Y, Y98L, G100V, G100N, G100K, G100T, R102K, S106L, S106K, or S106A. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof comprises one or more amino acid mutations selected from Q37Y, A38Y, R52I and / or T67V in a heavy chain variable domain of SEQ ID NO: 1. ii. Modifications in FRs Provided herein are humanized or de-immunized antibodies, fragments thereof, and antigen binding domains that specifically bind CDH17 proteins. In some embodiments, the antibodies, fragments thereof, and antigen binding domains comprise any one of the sequences for Table 5. 64 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Table 5 of VHH domains SEQ ID NO:Sequence110QVQLQESGGGLVQPGGSTRLSCVSSRTFSYYDMGWFRQAPGKEREFVAL T L T L T L T L T L T L T L T L T L T L T L T L T 65 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 123QVQLVESGGGLVQPGGSLRLSCVASRTFSYYDMGWFRQAPGKERELVAL LSWRGNNAEYSDSVMGRFTVSRGNTQNSVNLQMNNLKPEDTGIYYCAVT L T L T L T L T L T 6 In some embodiments, provided herein are CDH17 binding proteins comprising an amino acid sequence of any one of SEQ ID NOS: 110-128 and 133-151. In some embodiments, the CDH17 binding proteins include amino acid sequences of SEQ ID NOS: 41, 47, 72, and 129-132. In some embodiments, a humanized or de-immunized antibody, fragment thereof, and antigen binding domain that binds CDH17 includes framework regions of an antibody heavy chain variable region such as a FR1 region, a FR2 region, a FR3, region and a FR4 region having a consensus sequence set forth in Table 5. Such an antibody can include any of the CDRs of an antibody heavy chain variable region set forth in the above tables including Tables 3 and 4, and the accompanying descriptions. In some embodiments, a humanized or de-immunized antibody, fragment thereof, and antigen binding domain that binds CDH17 comprises an amino acid sequence of SEQ ID NO: 66 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 109 and one or more amino acid substitutions in one or more framework regions such that the humanized or de-immunized antibody, fragment thereof, and antigen binding domain has reduced immunogenicity in a human subject. The anti-CDH17 antibodies or antigen-binding domain thereof described herein may be modified by at least one amino acid substitution, deletion or insertion, wherein the variant anti-CDH17 antibodies or antigen-binding domain thereof substantially retains the biological characteristics of the unmodified protein, such as binding to CDH17. In some embodiments, the variant anti-CDH17 antibodies or antigen- binding domain thereof includes additional biological characteristics compared to the unmodified protein, such as humanization or de-immunization. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof may be modified by the substitution, deletion or insertion of 1 amino acid to 10 amino acids. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof may have 1 amino acid to 2 amino acids, 1 amino acid to 3 amino acids, 1 amino acid to 4 amino acids, 1 amino acid to 5 amino acids, 1 amino acid to 6 amino acids, 1 amino acid to 7 amino acids, 1 amino acid to 8 amino acids, 1 amino acid to 9 amino acids, 1 amino acid to 10 amino acids, 2 amino acids to 3 amino acids, 2 amino acids to 4 amino acids, 2 amino acids to 5 amino acids, 2 amino acids to 6 amino acids, 2 amino acids to 7 amino acids, 2 amino acids to 8 amino acids, 2 amino acids to 9 amino acids, 2 amino acids to 10 amino acids, 3 amino acids to 4 amino acids, 3 amino to 5 amino acids, 3 amino acids to 6 amino acids, 3 amino acids to 7 amino acids, 3 amino acids to 8 amino acids, 3 amino acids to 9 amino acids, 3 amino acids to 10 amino acids, 4 amino acids to 5 amino acids, 4 amino acids to 6 amino acids, 4 amino acids to 7 amino acids, 4 amino acids to 8 amino acids, 4 amino acids to 9 amino acids, 4 amino acids to 10 amino acids, 5 amino acids to 6 amino acids, 5 amino acids to 7 amino acids, 5 amino acids to 8 amino acids, 5 amino acids to 9 amino acids, 5 amino acids to 10 amino acids, 6 amino acids to 7 amino acids, 6 amino acids to 8 amino acids, 6 amino acids to 9 amino acids, 6 amino acids to 10 amino acids, 7 amino acids to 8 amino acids, 7 amino acids to 9 amino acids, 7 amino acids to 10 amino acids, 8 amino acids to 9 amino acids, 8 amino acids to 10 amino acids, or 9 amino acids to 10 amino acids modifications. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof may have 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, or 10 amino acids modifications. In some embodiments, the anti- CDH17 antibodies or antigen-binding domain thereof may have at least 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 67 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO amino acids, or 9 amino acids modification. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof may have at most 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, or 10 amino acids modification. In some embodiments, the anti-CDH17 antibodies or antigen-binding domain thereof as disclosed herein engineered to reduce immunogenicity in a human subject and comprising an amino acid sequence having at least 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 109. For example, the amino acid sequence of the anti-CDH17 antibodies or antigen-binding domain thereof can be between 80% and about 100% identical to the polypeptide sequence of SEQ ID NO: 109. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen- binding domains thereof as disclosed herein can comprise SEQ ID NO: 109 and one or more amino acid substitutions selected from the group consisting of Q4V, T17L, S23A, E42G, F45L, F45W, V68I, T73W, Q74K, N83S, K85R, G90A, I91V, Q112L, Q4V / T17L, Q4V / T17L / V68I, Q4V / F45L, T17L / E42G, T17L / V68I, F45L / V68I, F45W / V68I, Q4V / T17L / S23A, T17L / S23A, Q4V / T17L / F45W, Q4V / T17L / S23A / F45L, Q4V / T17L / F45W / V68I, Q4V / T17L / E42G / V68I, Q4V / T17L / F45W / V68I, T17L / E42G / V68I, Q4V / T17L / V68I, V68I / T73S, V68I / Q74K, V68I / T73S / Q74K, V68I / N83S / G90A, V68I / T73S / Q74K / N83S, V68I / Q74K / N83S, V68I / N83S / G90A / Q112L, V68I / Q74K / N83S / K85R, V68I / Q74K / N83S / K85R / G90A, V68I / N83S / G90A / I91V / Q112L, V68I / N83S / K85R / G90A / I91V, V68I / T73S / Q74K / N83S / K85R / G90A, V68I / Q74K / N83S / K85R / G90A, S59A / V68I / Q74K / N83S / K85R / G90A, Q4V / T17L / F45W / V68I / N83S / K85R / G90A, V68I / T73S / Q74K / N83W / K85R / G90A, V68I / N83S / K85R / G90A, Q4V / T17L / F45W / V68I / N83S / G90A / I91V / Q112L, Q4V / T17L / E42G / K85R, T17L / E42G / V68I / N83S / G90A, Q4V / T17L / V68I / N83S / G90A / Q112L, T17L / V68I / N83S / G90A, Q4V / T17L / S23A / F45L / Q112L, Q4V / F45L / Q112L, V68I / Q74K / N83S / K85R / G90A, Q4V / T17L / F45L / Q112L, F45W / V68I / T73S / Q74K / N83S / K85R / G90A, F45W / V68I / Q74K / N83S / K85R / G90A, and any combination thereof, where the numbering is based on the N-terminus Q residue as amino acid position 0. In some embodiments, the anti- CDH17 antibodies, fragments thereof, or antigen-binding domains thereof as disclosed herein 68 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO exhibit lower immunogenicity compared to comparable anti-CDH17 antibodies, fragments thereof, or antigen-binding domains thereof having the amino acid sequence of SEQ ID NO: 109. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen- binding domains thereof exhibiting lower immunogenicity than SEQ ID NO: 109 can comprise SEQ ID NO: 109 and amino acid substitutions V68I / Q74K / N83S / K85R / G90A, where the numbering is based on the N-terminus glutamine (Q) residue as amino acid position 0. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen- binding domain thereof comprises SEQ ID NO: 125. In some embodiments, such polypeptides do not include an amino acid substitution selected from the group consisting of G71D, N78Y, T73S, F74W, S59A, G71D / N78Y, T73S / N78Y, G71D / T73S, F45W / G71D, F45W / N78Y, F45W / T73S, G71D / T73S / N78Y, F45W / G71D / N78Y, F45W / T73S / N78Y, F45W / T73D / N78Y, F45W / G71D / V77L, G71D / T73S / V77L / N78Y, G71D / T73S / V77L / P86A, G71D / V77L / N78Y / I91V, G71D / T73S / N78Y / I91V, G71D / T73S / V77L / I91V, F45W / G71D / N78Y / N78Y, F45W / G71D / V77L / N78Y, G71D / T73S / V77L / N78Y / I91V, G71D / T73S / V77L / N78Y / P86A, G71D / T73S / V77L / P86A / I91V, G71D / T73S / N78Y / P86A / I91V, G71D / V77L / N78Y / P86A / I91V, Q4V / T17L / S23A / E42G / I91V, S23A / F35V / G71D / N78Y / I91V, F45W / G71D / T73S / V77L / N78Y, T17L / R43L / F45W / G71D / V77L / N78Y / I91V, Q0E / Q4V / T17L / G71D / T73A / V77L / I91V, T17L / S23A / E42G / R43L / F45W / G71D / V77L, Q0E / T17L / G71D / V77L / N78Y / S106Y / Q112L, S23A / F35V / R43L / F45W / G71D / N78Y / Q112L, Q4V / F35V / R43L / F45W / G71D / A101S / Q112L, Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / P86A, Q0E / Q4V / F35V / R43L / F45W / G71D / V77L / Q112L, Q0E / Q4V / T17S / S23A / T73A / V77L / P86A / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / P86A / Q112L, Q0E / Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / I91V, and Q0E / Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / Q112L. In some embodiments, the anti- CDH17 antibodies, fragments thereof, or antigen-binding domains thereof exhibiting lower immunogenicity than SEQ ID NO: 109 and comprises at least about 90%, about 91%, about 69 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% sequence identity to SEQ ID NO: 109 and not amino acid substitution(s) selected from the group consisting of G71D, N78Y, T73S, F74W, S59A, G71D / N78Y, T73S / N78Y, G71D / T73S, F45W / G71D, F45W / N78Y, F45W / T73S, G71D / T73S / N78Y, F45W / G71D / N78Y, F45W / T73S / N78Y, F45W / T73D / N78Y, F45W / G71D / V77L, G71D / T73S / V77L / N78Y, G71D / T73S / V77L / P86A, G71D / V77L / N78Y / I91V, G71D / T73S / N78Y / I91V, G71D / T73S / V77L / I91V, F45W / G71D / N78Y / N78Y, F45W / G71D / V77L / N78Y, G71D / T73S / V77L / N78Y / I91V, G71D / T73S / V77L / N78Y / P86A, G71D / T73S / V77L / P86A / I91V, G71D / T73S / N78Y / P86A / I91V, G71D / V77L / N78Y / P86A / I91V, Q4V / T17L / S23A / E42G / I91V, S23A / F35V / G71D / N78Y / I91V, F45W / G71D / T73S / V77L / N78Y, T17L / R43L / F45W / G71D / V77L / N78Y / I91V, Q0E / Q4V / T17L / G71D / T73A / V77L / I91V, T17L / S23A / E42G / R43L / F45W / G71D / V77L, Q0E / T17L / G71D / V77L / N78Y / S106Y / Q112L, S23A / F35V / R43L / F45W / G71D / N78Y / Q112L, Q4V / F35V / R43L / F45W / G71D / A101S / Q112L, Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / P86A, Q0E / Q4V / F35V / R43L / F45W / G71D / V77L / Q112L, Q0E / Q4V / T17S / S23A / T73A / V77L / P86A / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / P86A / Q112L, Q0E / Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / I91V, and Q0E / Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / Q112L. In some embodiments, the anti- CDH17 antibodies, fragments thereof, or antigen-binding domains thereof exhibiting lower immunogenicity than SEQ ID NO: 109 and comprises at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% sequence identity to SEQ ID NO: 125 and not amino acid substitution(s) selected from the group consisting of G71D, N78Y, T73S, F74W, S59A, G71D / N78Y, T73S / N78Y, G71D / T73S, F45W / G71D, F45W / N78Y, F45W / T73S, G71D / T73S / N78Y, F45W / G71D / N78Y, F45W / T73S / N78Y, F45W / T73D / N78Y, F45W / G71D / V77L, G71D / T73S / V77L / N78Y, G71D / T73S / V77L / P86A, G71D / V77L / N78Y / I91V, G71D / T73S / N78Y / I91V, G71D / T73S / V77L / I91V, F45W / G71D / N78Y / N78Y, F45W / G71D / V77L / N78Y, G71D / T73S / V77L / N78Y / I91V, G71D / T73S / V77L / N78Y / P86A, G71D / T73S / V77L / P86A / I91V, G71D / T73S / N78Y / P86A / I91V, 70 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO G71D / V77L / N78Y / P86A / I91V, Q4V / T17L / S23A / E42G / I91V, S23A / F35V / G71D / N78Y / I91V, F45W / G71D / T73S / V77L / N78Y, T17L / R43L / F45W / G71D / V77L / N78Y / I91V, Q0E / Q4V / T17L / G71D / T73A / V77L / I91V, T17L / S23A / E42G / R43L / F45W / G71D / V77L, Q0E / T17L / G71D / V77L / N78Y / S106Y / Q112L, S23A / F35V / R43L / F45W / G71D / N78Y / Q112L, Q4V / F35V / R43L / F45W / G71D / A101S / Q112L, Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / P86A, Q0E / Q4V / F35V / R43L / F45W / G71D / V77L / Q112L, Q0E / Q4V / T17S / S23A / T73A / V77L / P86A / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / P86A / Q112L, Q0E / Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / I91V, and Q0E / Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / Q112L. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen- binding domains thereof exhibiting lower immunogenicity than SEQ ID NO: 109 can comprise SEQ ID NO: 109 and amino acid substitutions of Q4V / T17L / S23A / F45L / Q112L, where the numbering is based on the N-terminus glutamine (Q) residue as amino acid position 0. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen- binding domain thereof comprises SEQ ID NO: 123. In some embodiments, such polypeptides comprise SEQ ID NO: 109 and not amino acid substitutions Q4V / T17L / S23A / F45L / R70L / Q112L, Q4V / T17L / S23A / F45L / V68I / Q74K / Q112L, Q4V / T17L / S23A / F45L / V68I / Q74K / V77L / N83S / G90A / Q112L, and Q4V / T17L / S23A / F45L / Q112L. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen-binding domains thereof exhibiting lower immunogenicity than SEQ ID NO: 109 and comprises at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% sequence identity to SEQ ID NO: 109 and not an amino acid substitution selected from the group consisting of Q4V / T17L / S23A / F45L / R70L / Q112L, Q4V / T17L / S23A / F45L / V68I / Q74K / Q112L, Q4V / T17L / S23A / F45L / V68I / Q74K / V77L / N83S / G90A / Q112L, and Q4V / T17L / S23A / F45L / Q112L. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen-binding domains thereof exhibiting lower immunogenicity than 71 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO SEQ ID NO: 109 and comprises at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% sequence identity to SEQ ID NO: 123 and not an amino acid substitution selected from the group consisting of S23A, S23A / R70L, S23A / V68I / Q74K, and S23A / V68I / Q74K / V77L / N83S / G90A. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen- binding domains thereof exhibiting lower immunogenicity than SEQ ID NO: 109 can comprise SEQ ID NO: 109 and amino acid substitutions of Q4V / T17L / S23A / F45L / Q112L, where the numbering is based on the N-terminus glutamine (Q) residue as amino acid position 0. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen- binding domain thereof comprises SEQ ID NO: 126. In some embodiments, such polypeptides do not include amino acid substitutions selected from the group consisting of Q4V / T17L / F45L / V68I / Q74K / V77L / N83S / G90A / Q112L, Q4V / T17L / F45L / R70L / Q112L, Q4V / T17L / S23A / F45L / R70L / Q112L, Q4V / T17L / S23A / F45L / V68I / Q74K / Q112L, Q4V / T17L / S23A / F45L / V68I / Q74K / V77L / N83S / G90A / Q112L, and Q4V / T17L / F45L / V68I / Q74K / Q112L. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen-binding domains thereof exhibiting lower immunogenicity than SEQ ID NO: 109 and comprises at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% sequence identity to SEQ ID NO: 109 and not amino acid substitutions Q4V / T17L / F45L / V68I / Q74K / V77L / N83S / G90A / Q112L, Q4V / T17L / F45L / R70L / Q112L, Q4V / T17L / S23A / F45L / R70L / Q112L, Q4V / T17L / S23A / F45L / V68I / Q74K / Q112L, Q4V / T17L / S23A / F45L / V68I / Q74K / V77L / N83S / G90A / Q112L, and Q4V / T17L / F45L / V68I / Q74K / Q112L. In some embodiments, the anti-CDH17 antibodies, fragments thereof, or antigen-binding domains thereof exhibiting lower immunogenicity than SEQ ID NO: 109 and not amino acid substitution(s) S23A, R70L, S23A / R70L, V68I / Q74K, S23A / F45L / V68I / Q74K, V68I / Q74K / V77L / N83S / G90A, and S23A / V68I / Q74K / V77L / N83S / G90A. iii. VHH Fc Fusion Proteins Also provided herein are ADCs and Fc fusion proteins containing humanized or de- immunized antibodies, fragments thereof, and antigen binding domains that specifically bind CDH17 proteins. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and 72 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO antigen-binding domains of the ADCs and Fc fusion proteins include any one of the sequences of SEQ ID NOS: 133-151 in Table 6. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 133. In some embodiments, the anti- CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 134. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 135. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 136. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 137. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen- binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 138. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 139. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 141. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 143. In some embodiments, the anti- CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 144. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 145. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 146. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 73 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 147. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen- binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 148. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 149. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 150. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence of SEQ ID NO: 151. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen- binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 133. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 134. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 135. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 136. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 137. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 138. In 74 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 139. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 140. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 141. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 142. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 143. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 144. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 145. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 146. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 75 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 147. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 148. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 149. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 150. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to SEQ ID NO: 151. Table 6 of VHH-Fc domains SEQ ID NO: Sequence L T S K S Q H L T S K S Q H 76 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 135QVQLQESGGGLVQPGGSTRLSCVSSRTFSYYDMGWFRQAPGKEREFVAL LSWRGNNAEYSDSVMGRFTISRGNSKNSVNLQMNSLRPEDTAIYYCAVT S K S Q H L T S K S Q H L T S K S Q H L T S K S Q H L T S K S Q H L T S K S 77 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO KAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH L T S K S Q H L T S K S Q H L T S K S Q H L T S K S Q H L T S K S Q H L T 78 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO YGGARSVRSWGQGTLVTVSSGGGGSEPKSSDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK S Q H L T S K S Q H L T S K S Q H L T S K S Q H L T S K S Q H L T S K S Q 79 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPGK , , , g domain thereof, or Fc fusion protein comprises a peptide linker. In some instances, the peptide linker may be a flexible linker, a rigid linker, a non-cleavable linker, or a cleavable linker. In some embodiments, the peptide linker may link a portion of a heavy chain variable domain to a portion of an Fc domain. The polypeptide described herein can be optimized for protein expression and yield by changing composition and / or length of the peptide linker. In some embodiments, the peptide linker can be about 2 amino acids to about 24 amino acids. In some embodiments, the peptide linker may be about 2 amino acids to about 4 amino acids, about 2 amino acids to about 6 amino acids, about 2 amino acids to about 8 amino acids, about 2 amino acids to about 10 amino acids, about 2 amino acids to about 12 amino acids, about 2 amino acids to about 14 amino acids, about 2 amino acids to about 16 amino acids, about 2 amino acids to about 18 amino acids, about 2 amino acids to about 20 amino acids, about 2 amino acids to about 22 amino acids, about 2 amino acids to about 24 amino acids, about 4 amino acids to about 6 amino acids, about 4 amino acids to about 8 amino acids, about 4 amino acids to about 10 amino acids, about 4 amino acids to about 12 amino acids, about 4 amino acids to about 14 amino acids, about 4 amino acids to about 16 amino acids, about 4 amino acids to about 18 amino acids, about 4 amino acids to about 20 amino acids, about 4 amino acids to about 22 amino acids, about 4 amino acids to about 24 amino acids, about 6 amino acids to about 8 amino acids, about 6 amino acids to about 10 amino acids, about 6 amino acids to about 12 amino acids, about 6 amino acids to about 14 amino acids, about 6 amino acids to about 16 amino acids, about 6 amino acids to about 18 amino acids, about 6 amino acids to about 20 amino acids, about 6 amino acids to about 22 amino acids, about 6 amino acids to about 24 amino acids, about 8 amino acids to about 10 amino acids, about 8 amino acids to about 12 amino acids, about 8 amino acids to about 14 amino acids, about 8 amino acids to about 16 amino acids, about 8 amino acids to about 18 amino acids, about 8 amino acids to about 20 amino acids, about 8 amino acids to about 22 amino acids, about 8 amino acids to about 24 amino acids, about 10 amino acids to about 12 amino acids, about 10 amino acids to about 14 amino acids, about 10 amino acids to about 16 amino acids, about 10 amino acids to about 18 amino acids, about 10 amino acids to about 20 amino acids, about 10 amino acids to about 22 amino acids, about 10 amino acids to about 24 amino acids, 80 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO about 12 amino acids to about 14 amino acids, about 12 amino acids to about 16 amino acids, about 12 amino acids to about 18 amino acids, about 12 amino acids to about 20 amino acids, about 12 amino acids to about 22 amino acids, about 12 amino acids to about 24 amino acids, about 14 amino acids to about 16 amino acids, about 14 amino acids to about 18 amino acids, about 14 amino acids to about 20 amino acids, about 14 amino acids to about 22 amino acids, about 14 amino acids to about 24 amino acids, about 16 amino acids to about 18 amino acids, about 16 amino acids to about 20 amino acids, about 16 amino acids to about 22 amino acids, about 16 amino acids to about 24 amino acids, about 18 amino acids to about 20 amino acids, about 18 amino acids to about 22 amino acids, about 18 amino acids to about 24 amino acids, about 20 amino acids to about 22 amino acids, about 20 amino acids to about 24 amino acids, or about 22 amino acids to about 24 amino acids. In some embodiments, the polypeptide linker can be about 2 amino acids, about 4 amino acids, about 6 amino acids, about 8 amino acids, about 10 amino acids, about 12 amino acids, about 14 amino acids, about 16 amino acids, about 18 amino acids, about 20 amino acids, about 22 amino acids, or about 24 amino acids. In some embodiments, the polypeptide linker can be at least about 2 amino acids, about 4 amino acids, about 6 amino acids, about 8 amino acids, about 10 amino acids, about 12 amino acids, about 14 amino acids, about 16 amino acids, about 18 amino acids, about 20 amino acids, or about 22 amino acids. In some embodiments, the polypeptide linker may at most about 4 amino acids, about 6 amino acids, about 8 amino acids, about 10 amino acids, about 12 amino acids, about 14 amino acids, about 16 amino acids, about 18 amino acids, about 20 amino acids, about 22 amino acids, or about 24 amino acids. In some embodiments, the peptide linker comprises (G4S)n, (SG4)n, G4(SG4)n or G2(SG2)n, wherein n can be 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, the peptide linker comprises GGGGSGGGGS (SEQ ID NO: 100). In some embodiments, the peptide linker comprises GGGGS (SEQ ID NO: 101). Exemplary peptide linker sequences are listed in Table 7 below. Table 7 of Peptide Linkers Sequence SEQ ID NO: 81 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO GSGSGSGSGS 104 GSGSGSGSGSGS 105 he separate domains or portions to fold independently of each other can include glycine-serine based linkers, glycine-proline based linkers and proline-alanine based linkers. In some embodiments, the linker is a glycine- serine based linker. These linkers comprise glycine and serine residues and may be between 8 and 50, 10 and 30, and 10 and 20 amino acids in length. In some embodiments, the linker is a glycine-proline based linker. These linkers comprise glycine and proline residues and may be between 3 and 30, 10 and 30, and 3 and 20 amino acids in length. In some embodiments, the linker is a proline-alanine based linker. These linkers comprise proline and alanine residues and may be between 3 and 30, 10 and 30, 3 and 20 and 6 and 18 amino acids in length. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen- binding domains of the ADCs and Fc fusion proteins include any one of the consensus framework sequences in Table 5, a hinge region of Table 7, and a Fc domain of human IgG1 of Table 7. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an Fc domain including hinge region of human IgG4 as set forth in Uniprot Ref. No. P01861. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an Fc domain of human IgG3 including hinge region as set forth in Uniprot Ref. No. P01860. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an Fc domain of human IgG2 including hinge region as set forth in Uniprot Ref. No. P01859. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an Fc domain of human IgG1 including hinge region as set forth in Uniprot Ref. No. P01857. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an Fc domain of human IgA including hinge region as set forth in Uniprot Ref. Nos. P01876 and P01877. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an Fc 82 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO domain of human IgD including hinge region as set forth in Uniprot Ref. No. P01880. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an Fc domain of human IgE including hinge region as set forth in Uniprot Ref. No. P01854. In some embodiments, the anti-CDH17 antibodies, fragments thereof, and antigen-binding domains of the ADCs and Fc fusion proteins include an Fc domain of human IgM including hinge region as set forth in Uniprot Ref. No. P01871. Table 8 of Other Antibody Domains SEQ ID Name NO: Se ence V V K P L G domains thereof described herein, any component described herein, and any amino acid sequence set forth in the sequence listing accompanying herewith can be included in any ADCs, Fc fusion proteins, or CDH17 binding polypeptide of the present disclosure. In some aspects, the antibodies, fragments thereof, and antigen-binding domains thereof and included in any ADCs, Fc fusion proteins, or CDH17 binding polypeptide described herein can include at least one variant Fc domain comprising one or more amino acid substitution that mediates heterodimerization such as knob-in-hole substitutions, improves Complement Dependent Cytotoxicity (CDC) function, improves antibody- dependent cellular cytotoxicity (ADCC) function, reduces fucosylation, improved effector functions, enhances serum half-life, reduces FcgammaR (e.g., FcγRI, FcγRII, and / or FcγRIII) binding, mediates neonatal Fc receptor (FcRn) binding, altered C1q binding, increased stability, and any combination thereof. In some embodiments, the knob mutation comprises T366W and the hole mutation comprises one or more T366S, L368A, and Y407V, wherein amino acid numbering is 83 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO according to the EU index. In some embodiments, heterodimeric Fc domains of an ADC, Fc fusion protein and anti-CDH17 polypeptide includes one Fc domain comprises D399K and E356K substitutions and another Fc domain comprises K409D and K392D substitutions. In some embodiments, one Fc domain comprises D399K, E356K, and E357K substitutions and another Fc domain comprises K409D, K392D, and K370D substitutions. In some embodiments, one or more amino acid substitutions include any at amino acid position 238, 265, 269, 270, 297, 327, and 329 of human IgG1 Fc region, where the residue numbering is of the EU index. In other embodiments, one or more amino acid substitutions include any at amino acid position 233, 234, 235, 236, 238, 239, 243, 247, 248, 249, 252, 254, 255, 256, 258, 265, 267, 268, 269, 270, 272, 276, 278, 280, 283, 285, 286, 289, 290, 292, 293, 294, 295, 296, 298, 301, 303, 305, 307, 309, 311, 312, 315, 320, 322, 324, 326, 327, 329, 330, 331, 332, 333, 334, 335, 337, 338, 339, 340, 360, 373, 376, 378, 382, 388, 389, 396, 398, 414, 416, 419, 430, 434, 435, 437, 438, and 439 of human gG1, IgG2, IgG3 or IgG4 Fc region, where the residue numbering is of the EU index. Exemplary amino acid substitution(s) based on EU numbering include, but are not limited to, E233L, L2341, L234Y, L235S, G236A, S239D, F243L, F243V, P2471, D280H, K290S, K290E, K290N, K290Y, R292P, E294L, Y296W, S298A, S298D, S298V, S298G, S298T, T299A, Y300L, V3051, Q311M, K326A, K326E, K326W, A330S, A330L, A330M, A330F, I332E, D333A, E333S, E333A, K334A, K334V, A339D, A339Q, P396L, or combinations thereof. In some embodiments, amino acid substitution(s) based on EU numbering of the variant Fc region include, but are not limited to, C220S, C226S, C229S, E233P, L234A, L234V, V234A, L234F, L235A, L235E, G237A, P238S, S267E, H268Q, N297A, N297G, V309L, E318A, L328F, A330S, A331S, P331S or combinations thereof. In some embodiments, the variant Fc region includes a substitution selected from the group consisting of S228P, E233P, L234A, L235A, L235E, N297A, N297D, N297G, or P331S of human IgG1 or IgG4. In some instances, the variant Fc region includes L234A / L235A / P329G of an human IgG1 Fc region. Other exemplary variant Fc regions are described in US20030157108A1, US5648260A, US6737056B1, US7335742B2, US8969526B2, and US11104745B2. iv. Antibody Properties In some embodiments, immunogenicity of the humanized or de-immunized anti- CDH17 antibody or antigen-binding domain described herein is about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 84 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, or about 5.0 fold lower or reduced than the immunogenicity of an anti- CDH17 antibody or antigen-binding domain of SEQ ID NO: 1 or SEQ ID NO: 109. In some embodiments, immunogenicity of the humanized or de-immunized anti- CDH17 antibody or antigen-binding domain described herein is about 2 fold, about 3 fold, about 4 fold, about 5 fold, about 6 fold, about 7 fold, about 8 fold, about 9 fold, about 10 fold, about 11 fold, about 12 fold, about 13 fold, about 14 fold, about 15 fold, about 16 fold, about 17 fold, about 18 fold, about 19 fold, or about 20 fold lower or reduced than the immunogenicity of an anti-CDH17 antibody or antigen-binding domain of SEQ ID NO: 1 or SEQ ID NO: 109. In some embodiments, immunogenicity of the humanized or de-immunized anti- CDH17 antibody or antigen-binding domain described herein is at least about 2 fold, at least about 3 fold, at least about 4 fold, at least about 5 fold, at least about 6 fold, at least about 7 fold, at least about 8 fold, at least about 9 fold, at least about 10 fold, at least about 11 fold, at least about 12 fold, at least about 13 fold, at least about 14 fold, at least about 15 fold, at least about 16 fold, at least about 17 fold, at least about 18 fold, at least about 19 fold, or at least about 20 fold lower or reduced than the immunogenicity of an anti-CDH17 antibody or antigen-binding domain of SEQ ID NO: 1 or SEQ ID NO: 109. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has substantially equivalent binding affinity to CDH17 compared to a binding affinity of an amino acid sequence as set out in SEQ ID NO: 109 to CDH17. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has an increased binding affinity to CDH17 compared to a binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is about 5-fold to about 15-fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is about 2 fold to about 5 fold, about 3 fold to 85 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO about 5 fold, about 4 fold to about 5 fold, about 5 fold to about 6 fold, about 5 fold to about 7 fold, about 5 fold to about 8 fold, about 5 fold to about 9 fold, about 5 fold to about 10 fold, about 5 fold to about 11 fold, about 5 fold to about 12 fold, about 5 fold to about 13 fold, about 5 fold to about 14 fold, about 5 fold to about 15 fold, about 7 fold to about 8 fold, about 7 fold to about 9 fold, about 7 fold to about 10 fold, about 7 fold to about 11 fold, about 7 fold to about 12 fold, about 7 fold to about 13 fold, about 7 fold to about 14 fold, about 7 fold to about 15 fold, about 10 fold to about 11 fold, about 10 fold to about 12 fold, about 10 fold to about 13 fold, about 10 fold to about 14 fold, or about 10 fold to about 15 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is about 2 fold, about 3 fold, about 4 fold, about 5 fold, about 6 fold, about 7 fold, about 8 fold, about 9 fold, about 10 fold, about 11 fold, about 12 fold, about 13 fold, about 14 fold, about 15 fold, about 16 fold, about 17 fold, about 18 fold, about 19 fold, or about 20 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at least about 2 fold, about 3 fold, about 4 fold, about 5 fold, about 6 fold, about 7 fold, about 8 fold, about 9 fold, about 10 fold, about 11 fold, about 12 fold, about 13 fold, about 14 fold, about 15 fold, about 16 fold, about 17 fold, about 18 fold, about 19 fold, or about 20 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at most about 3 fold, about 4 fold, about 5 fold, about 6 fold, about 7 fold, about 8 fold, about 9 fold, about 10 fold, about 11 fold, about 12 fold, about 13 fold, about 14 fold, about 15 fold, about 16 fold, about 17 fold, about 18 fold, about 19 fold, or about 20 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen- binding domain thereof to CDH17 is about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 86 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, or about 5.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at least about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, or about 5.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at most about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, or about 5.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen- binding domain thereof to CDH17 is about 5.1 fold, about 5.2 fold, about 5.3 fold, about 5.4 fold, about 5.5 fold, about 5.6 fold, about 5.7 fold, about 5.8 fold, about 5.9 fold, about 6.0 fold, about 6.1 fold, about 6.2 fold, about 6.3 fold, about 6.4 fold, about 6.5 fold, about 6.6 fold, about 6.7 fold, about 6.8 fold, about 6.9 fold, about 7.0 fold, about 7.1 fold, about 7.2 fold, about 7.3 fold, about 7.4 fold, about 7.5 fold, about 7.6 fold, about 7.7 fold, about 7.8 fold, about 7.9 fold, about 8.0 fold, about 8.1 fold, about 8.2 fold, about 8.3 fold, about 8.4 fold, about 8.5 fold, about 8.6 fold, about 8.7 fold, about 8.8 fold, about 8.9 fold, about 9.0 fold, about 9.1 fold, about 9.2 fold, about 9.3 fold, about 9.4 fold, about 9.5 fold, about 9.6 fold, about 9.7 fold, about 9.8 fold, about 9.9 fold or about 10.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some 87 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at least about 5.1 fold, about 5.2 fold, about 5.3 fold, about 5.4 fold, about 5.5 fold, about 5.6 fold, about 5.7 fold, about 5.8 fold, about 5.9 fold, about 6.0 fold, about 6.1 fold, about 6.2 fold, about 6.3 fold, about 6.4 fold, about 6.5 fold, about 6.6 fold, about 6.7 fold, about 6.8 fold, about 6.9 fold, about 7.0 fold, about 7.1 fold, about 7.2 fold, about 7.3 fold, about 7.4 fold, about 7.5 fold, about 7.6 fold, about 7.7 fold, about 7.8 fold, about 7.9 fold, about 8.0 fold, about 8.1 fold, about 8.2 fold, about 8.3 fold, about 8.4 fold, about 8.5 fold, about 8.6 fold, about 8.7 fold, about 8.8 fold, about 8.9 fold, about 9.0 fold, about 9.1 fold, about 9.2 fold, about 9.3 fold, about 9.4 fold, about 9.5 fold, about 9.6 fold, about 9.7 fold, about 9.8 fold, about 9.9 fold or about 10.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at most about 5.1 fold, about 5.2 fold, about 5.3 fold, about 5.4 fold, about 5.5 fold, about 5.6 fold, about 5.7 fold, about 5.8 fold, about 5.9 fold, about 6.0 fold, about 6.1 fold, about 6.2 fold, about 6.3 fold, about 6.4 fold, about 6.5 fold, about 6.6 fold, about 6.7 fold, about 6.8 fold, about 6.9 fold, about 7.0 fold, about 7.1 fold, about 7.2 fold, about 7.3 fold, about 7.4 fold, about 7.5 fold, about 7.6 fold, about 7.7 fold, about 7.8 fold, about 7.9 fold, about 8.0 fold, about 8.1 fold, about 8.2 fold, about 8.3 fold, about 8.4 fold, about 8.5 fold, about 8.6 fold, about 8.7 fold, about 8.8 fold, about 8.9 fold, about 9.0 fold, about 9.1 fold, about 9.2 fold, about 9.3 fold, about 9.4 fold, about 9.5 fold, about 9.6 fold, about 9.7 fold, about 9.8 fold, about 9.9 fold or about 10.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen- binding domain thereof to CDH17 is about 10.1 fold, about 10.2 fold, about 10.3 fold, about 10.4 fold, about 10.5 fold, about 10.6 fold, about 10.7 fold, about 10.8 fold, about 10.9 fold, about 11.0 fold, about 11.1 fold, about 11.2 fold, about 11.3 fold, about 11.4 fold, about 11.5 fold, about 11.6 fold, about 11.7 fold, about 11.8 fold, about 11.9 fold, about 12.0 fold, about 12.1 fold, about 12.2 fold, about 12.3 fold, about 12.4 fold, about 12.5 fold, about 12.6 fold, about 12.7 fold, about 12.8 fold, about 12.9 fold, about 13.0 fold, about 13.1 fold, about 13.2 fold, about 13.3 fold, about 13.4 fold, about 13.5 fold, about 13.6 fold, about 13.7 fold, about 13.8 fold, about 13.9 fold, about 14.0 fold, about 14.1 fold, about 14.2 fold, about 14.3 fold, about 14.4 fold, about 14.5 fold, about 14.6 fold, about 14.7 fold, about 14.8 fold, about 14.9 88 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO fold, or about 15.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at least about 10.1 fold, about 10.2 fold, about 10.3 fold, about 10.4 fold, about 10.5 fold, about 10.6 fold, about 10.7 fold, about 10.8 fold, about 10.9 fold, about 11.0 fold, about 11.1 fold, about 11.2 fold, about 11.3 fold, about 11.4 fold, about 11.5 fold, about 11.6 fold, about 11.7 fold, about 11.8 fold, about 11.9 fold, about 12.0 fold, about 12.1 fold, about 12.2 fold, about 12.3 fold, about 12.4 fold, about 12.5 fold, about 12.6 fold, about 12.7 fold, about 12.8 fold, about 12.9 fold, about 13.0 fold, about 13.1 fold, about 13.2 fold, about 13.3 fold, about 13.4 fold, about 13.5 fold, about 13.6 fold, about 13.7 fold, about 13.8 fold, about 13.9 fold, about 14.0 fold, about 14.1 fold, about 14.2 fold, about 14.3 fold, about 14.4 fold, about 14.5 fold, about 14.6 fold, about 14.7 fold, about 14.8 fold, about 14.9 fold, or about 15.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at most about 10.1 fold, about 10.2 fold, about 10.3 fold, about 10.4 fold, about 10.5 fold, about 10.6 fold, about 10.7 fold, about 10.8 fold, about 10.9 fold, about 11.0 fold, about 11.1 fold, about 11.2 fold, about 11.3 fold, about 11.4 fold, about 11.5 fold, about 11.6 fold, about 11.7 fold, about 11.8 fold, about 11.9 fold, about 12.0 fold, about 12.1 fold, about 12.2 fold, about 12.3 fold, about 12.4 fold, about 12.5 fold, about 12.6 fold, about 12.7 fold, about 12.8 fold, about 12.9 fold, about 13.0 fold, about 13.1 fold, about 13.2 fold, about 13.3 fold, about 13.4 fold, about 13.5 fold, about 13.6 fold, about 13.7 fold, about 13.8 fold, about 13.9 fold, about 14.0 fold, about 14.1 fold, about 14.2 fold, about 14.3 fold, about 14.4 fold, about 14.5 fold, about 14.6 fold, about 14.7 fold, about 14.8 fold, about 14.9 fold, or about 15.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen- binding domain thereof to CDH17 is about 15.1 fold, about 15.2 fold, about 15.3 fold, about 15.4 fold, about 15.5 fold, about 15.6 fold, about 15.7 fold, about 15.8 fold, about 15.9 fold, about 16.0 fold, about 16.1 fold, about 16.2 fold, about 16.3 fold, about 16.4 fold, about 16.5 fold, about 16.6 fold, about 16.7 fold, about 16.8 fold, about 16.9 fold, about 17.0 fold, about 17.1 fold, about 17.2 fold, about 17.3 fold, about 17.4 fold, about 17.5 fold, about 17.6 fold, about 17.7 fold, about 17.8 fold, about 17.9 fold, about 18.0 fold, about 18.1 fold, about 18.2 89 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO fold, about 18.3 fold, about 18.4 fold, about 18.5 fold, about 18.6 fold, about 18.7 fold, about 18.8 fold, about 18.9 fold, about 19.0 fold, about 19.1 fold, about 19.2 fold, about 19.3 fold, about 19.4 fold, about 19.5 fold, about 19.6 fold, about 19.7 fold, about 19.8 fold, about 19.9 fold or about 20.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at least about 15.1 fold, about 15.2 fold, about 15.3 fold, about 15.4 fold, about 15.5 fold, about 15.6 fold, about 15.7 fold, about 15.8 fold, about 15.9 fold, about 16.0 fold, about 16.1 fold, about 16.2 fold, about 16.3 fold, about 16.4 fold, about 16.5 fold, about 16.6 fold, about 16.7 fold, about 16.8 fold, about 16.9 fold, about 17.0 fold, about 17.1 fold, about 17.2 fold, about 17.3 fold, about 17.4 fold, about 17.5 fold, about 17.6 fold, about 17.7 fold, about 17.8 fold, about 17.9 fold, about 18.0 fold, about 18.1 fold, about 18.2 fold, about 18.3 fold, about 18.4 fold, about 18.5 fold, about 18.6 fold, about 18.7 fold, about 18.8 fold, about 18.9 fold, about 19.0 fold, about 19.1 fold, about 19.2 fold, about 19.3 fold, about 19.4 fold, about 19.5 fold, about 19.6 fold, about 19.7 fold, about 19.8 fold, about 19.9 fold or about 20.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at most about 15.1 fold, about 15.2 fold, about 15.3 fold, about 15.4 fold, about 15.5 fold, about 15.6 fold, about 15.7 fold, about 15.8 fold, about 15.9 fold, about 16.0 fold, about 16.1 fold, about 16.2 fold, about 16.3 fold, about 16.4 fold, about 16.5 fold, about 16.6 fold, about 16.7 fold, about 16.8 fold, about 16.9 fold, about 17.0 fold, about 17.1 fold, about 17.2 fold, about 17.3 fold, about 17.4 fold, about 17.5 fold, about 17.6 fold, about 17.7 fold, about 17.8 fold, about 17.9 fold, about 18.0 fold, about 18.1 fold, about 18.2 fold, about 18.3 fold, about 18.4 fold, about 18.5 fold, about 18.6 fold, about 18.7 fold, about 18.8 fold, about 18.9 fold, about 19.0 fold, about 19.1 fold, about 19.2 fold, about 19.3 fold, about 19.4 fold, about 19.5 fold, about 19.6 fold, about 19.7 fold, about 19.8 fold, about 19.9 fold or about 20.0 fold greater than the binding affinity of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a KD for binding to CDH17 of about 1.0 X 10-9to 5.0 X 10-8M. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a KD for binding to CDH17 of about 1.0 X 10-9M, about 2.0 X 10-9M, about 3.0 X 10-9M, about 4.0 X 10-9M, about 5.0 90 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO X 10-9M, about 6.0 X 10-9M, about 7.0 X 10-9M, about 8.0 X 10-9M, about 9.0 X 10-9M, about 10.0 X 10-9M, about 11.0 X 10-9M, about 12.0 X 10-9M, about 13.0 X 10-9M, about 14.0 X 10-9M, about 15.0 X 10-9M, about 16.0 X 10-9M, about 17.0 X 10-9M, about 18.0 X 10-9M, about 19.0 X 10-9M, about 20.0 X 10-9M, about 21.0 X 10-9M, about 22.0 X 10-9M, about 23.0 X 10-9M, about 24.0 X 10-9M, about 25.0 X 10-9M, about 26.0 X 10-9M, about 27.0 X 10-9M, about 28.0 X 10-9M, about 29.0 X 10-9M, about 30.0 X 10-9M, about 31.0 X 10-9M, about 32.0 X 10-9M, about 33.0 X 10-9M, about 34.0 X 10-9M, about 35.0 X 10-9M, about 36.0 X 10-9M, about 37.0 X 10-9M, about 38.0 X 10-9M, about 39.0 X 10-9M, about 40.0 X 10-9M, about 41.0 X 10-9M, about 42.0 X 10-9M, about 43.0 X 10-9M, about 44.0 X 10-9M, about 45.0 X 10-9M, about 46.0 X 10-9M, about 47.0 X 10-9M, about 48.0 X 10-9M, about 49.0 X 10-9M, or about 50.0 X 10-9M. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a KD for binding to CDH17 of less than 1.0 X 10-9M, about 2.0 X 10-9M, about 3.0 X 10-9M, about 4.0 X 10-9M, about 5.0 X 10-9M, about 6.0 X 10-9M, about 7.0 X 10-9M, about 8.0 X 10-9M, about 9.0 X 10-9M, about 10.0 X 10-9M, about 11.0 X 10-9M, about 12.0 X 10-9M, about 13.0 X 10-9M, about 14.0 X 10-9M, about 15.0 X 10-9M, about 16.0 X 10-9M, about 17.0 X 10-9M, about 18.0 X 10-9M, about 19.0 X 10-9M, about 20.0 X 10-9M, about 21.0 X 10-9M, about 22.0 X 10-9M, about 23.0 X 10-9M, about 24.0 X 10-9M, about 25.0 X 10-9M, about 26.0 X 10-9M, about 27.0 X 10-9M, about 28.0 X 10-9M, about 29.0 X 10-9M, about 30.0 X 10-9M, about 31.0 X 10-9M, about 32.0 X 10-9M, about 33.0 X 10-9M, about 34.0 X 10-9M, about 35.0 X 10-9M, about 36.0 X 10-9M, about 37.0 X 10-9M, about 38.0 X 10-9M, about 39.0 X 10-9M, about 40.0 X 10-9M, about 41.0 X 10-9M, about 42.0 X 10-9M, about 43.0 X 10-9M, about 44.0 X 10-9M, about 45.0 X 10-9M, about 46.0 X 10-9M, about 47.0 X 10-9M, about 48.0 X 10-9M, about 49.0 X 10-9M, or about 50.0 X 10-9M. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a KD for binding to CDH17 of at most 1.0 X 10-9M, about 2.0 X 10-9M, about 3.0 X 10-9M, about 4.0 X 10-9M, about 5.0 X 10-9M, about 6.0 X 10-9M, about 7.0 X 10-9M, about 8.0 X 10-9M, about 9.0 X 10-9M, about 10.0 X 10-9M, about 11.0 X 10-9M, about 12.0 X 10-9M, about 13.0 X 10-9M, about 14.0 X 10-9M, about 15.0 X 10-9M, about 16.0 X 10-9M, about 17.0 X 10-9M, about 18.0 X 10-9M, about 19.0 X 10-9M, about 20.0 X 10-9M, about 21.0 X 10-9M, about 22.0 X 10-9M, about 23.0 X 10-9M, about 24.0 X 10-9M, about 25.0 X 10-9M, about 26.0 X 10-9M, about 27.0 X 10-9M, about 28.0 X 10-9M, about 29.0 X 10-9M, about 30.0 X 10-9M, about 31.0 X 10-9M, about 32.0 X 10-9M, about 33.0 X 10-9M, about 34.0 X 10-9M, about 35.0 X 10-9M, about 36.0 X 10-9M, 91 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO about 37.0 X 10-9M, about 38.0 X 10-9M, about 39.0 X 10-9M, about 40.0 X 10-9M, about 41.0 X 10-9M, about 42.0 X 10-9M, about 43.0 X 10-9M, about 44.0 X 10-9M, about 45.0 X 10-9M, about 46.0 X 10-9M, about 47.0 X 10-9M, about 48.0 X 10-9M, about 49.0 X 10-9M, or about 50.0 X 10-9M. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof inhibits CDH17 activity with an IC50 of 50.0 X 10-12to 1000.0 X 10-12M. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof inhibits CDH17 activity with an IC50 of about 50.0 X 10-12M, about 60.0 X 10-12M, about 70.0 X 10-12M, about 80.0 X 10-12M, about 90.0 X 10-12M, about 100.0 X 10-12M, about 150.0 X 10-12M, about 200.0 X 10-12M, about 250.0 X 10-12M, about 300.0 X 10-12M, about 350.0 X 10-12M, about 400.0 X 10-12M, about 450.0 X 10-12M, about 500.0 X 10-12M, about 550.0 X 10-12M, about 600.0 X 10-12M, about 650.0 X 10-12M, about 700.0 X 10-12M, about 750.0 X 10-12M, about 800.0 X 10-12M, about 850.0 X 10-12M, about 900.0 X 10-12M, about 950.0 X 10-12M, or about 1000.0 X 10-12M. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof inhibits CDH17 activity with an IC50of less than about 50.0 X 10-12M, about 60.0 X 10-12M, about 70.0 X 10-12M, about 80.0 X 10-12M, about 90.0 X 10-12M, about 100.0 X 10-12M, about 150.0 X 10-12M, about 200.0 X 10-12M, about 250.0 X 10-12M, about 300.0 X 10-12M, about 350.0 X 10-12M, about 400.0 X 10-12M, about 450.0 X 10-12M, about 500.0 X 10-12M, about 550.0 X 10-12M, about 600.0 X 10-12M, about 650.0 X 10-12M, about 700.0 X 10-12M, about 750.0 X 10-12M, about 800.0 X 10-12M, about 850.0 X 10-12M, about 900.0 X 10-12M, about 950.0 X 10-12M, or about 1000.0 X 10-12M. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof inhibits CDH17 activity with an IC50 of at most about 50.0 X 10-12M, about 60.0 X 10-12M, about 70.0 X 10-12M, about 80.0 X 10-12M, about 90.0 X 10-12M, about 100.0 X 10-12M, about 150.0 X 10-12M, about 200.0 X 10-12M, about 250.0 X 10-12M, about 300.0 X 10-12M, about 350.0 X 10-12M, about 400.0 X 10-12M, about 450.0 X 10-12M, about 500.0 X 10-12M, about 550.0 X 10-12M, about 600.0 X 10-12M, about 650.0 X 10-12M, about 700.0 X 10-12M, about 750.0 X 10-12M, about 800.0 X 10-12M, about 850.0 X 10-12M, about 900.0 X 10-12M, about 950.0 X 10-12M, or about 1000.0 X 10-12M. In some embodiments, the IC50 of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is about 5-fold to about 30-fold lesser than the IC50of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the IC50 of the 92 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is about 5 fold to about 10 fold, about 5 fold to about 15 fold, about 5 fold to about 20 fold, about 5 fold to about 25 fold, about 5 fold to about 30 fold, about 10 fold to about 15 fold, about 10 fold to about 20 fold, about 10 fold to about 25 fold, about 10 fold to about 30 fold, about 15 fold to about 20 fold, about 15 fold to about 25 fold, or about 15 fold to about 30 fold lesser than the IC50 of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the IC50 of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is about 2 fold, about 3 fold, about 4 fold, about 5 fold, about 6 fold, about 7 fold, about 8 fold, about 9 fold, about 10 fold, about 11 fold, about 12 fold, about 13 fold, about 14 fold, about 15 fold, about 16 fold, about 17 fold, about 18 fold, about 19 fold, about 20 fold, about 21 fold, about 22 fold, about 23 fold, about 24 fold, about 25 fold, about 26 fold, about 27 fold, about 28 fold, about 29 fold, or about 30 fold lesser than the IC50of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the IC50 of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is at least about 2 fold, about 3 fold, about 4 fold, about 5 fold, about 6 fold, about 7 fold, about 8 fold, about 9 fold, about 10 fold, about 11 fold, about 12 fold, about 13 fold, about 14 fold, about 15 fold, about 16 fold, about 17 fold, about 18 fold, about 19 fold, about 20 fold, about 21 fold, about 22 fold, about 23 fold, about 24 fold, about 25 fold, about 26 fold, about 27 fold, about 28 fold, about 29 fold, or about 30 fold lesser than the IC50of an amino acid sequence as set out in SEQ ID NO: 1 to CDH17. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has increased stability compared to stability of an amino acid sequence as set out in SEQ ID NO: 1. In some embodiments, the stability of the anti-CDH17 antibody or antigen-binding domain thereof to CDH17 is measured by melting temperature (Tm). In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm between about 40 - 80 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of about 40 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of about 45 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of about 50 °C. In some embodiments, the anti- CDH17 antibody or antigen-binding domain thereof has a Tm of about 60 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of about 65 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of about 70 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding 93 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO domain thereof has a Tm of about 75 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of about 80 °C. In some embodiments, the anti- CDH17 antibody or antigen-binding domain thereof has a Tm of less than about 40 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of less than about 45 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of less than about 50 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of less than about 60 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of less than about 65 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of less than about 70 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of less than about 75 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a Tm of less than about 80 °C. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof has a higher purity compared to a purity of an amino acid sequence as set out in SEQ ID NO: 1. In some embodiments, purity is measured via capillary gel electrophoresis using sodium dodecyl sulfate (CE-SDS). In some embodiments, the anti-CDH17 antibody or antigen- binding domain thereof has a purity of 70%-100%, e.g., 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%. v. Exemplary Embodiments of Anti-CDH17 ADCs for Cancer In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 133 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 133 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker-monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 134 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second 94 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO monomer comprising SEQ ID NO: 134 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker-monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 135 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 135 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 136 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 136 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 137 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 137 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 138 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 138 and a second conjugation linker-payload is attached via the core 95 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 139 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 139 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 140 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 140 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 141 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 141 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO:142 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 142 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the 96 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker-monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 143 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 143 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 144 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 144 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 145 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 145 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, an CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 146 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 146 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly 97 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, an CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 147 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 147 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, an CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 148 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 148 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, an CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 149 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 149 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, an CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 150 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 150 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- 98 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. In some embodiments, an CDH17 targeting ADC includes a first monomer comprising SEQ ID NO: 151 and a first conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the first monomer, and a second monomer comprising SEQ ID NO: 151 and a second conjugation linker-payload is attached via the core GlcNAc for the antibody glycan at the N297 residue of the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a highly polar sulfamide-PEG moiety linked to a branched valine-citrulline dipeptide-PABC linker- monomethyl auristatin E (MMAE) and wherein the ADC is a DAR4 ADC. The ADC includes SYNstatin E linker-payloads. In some embodiments, provided herein are method of treating a CDH17-expressing cancer cell or tumor by administering any of the ADCs described herein to a patient. Provided herein are anti-CDH17 ADC containing a stable enzyme-catalyzed conjugation of a linker-payload to the antibody such that the linker-payload does not undergo spontaneous reversal of the specific conjugation in the presence of serum, thereby transferring the linker-payload to other serum proteins and non-specifically releasing the payload. Administration of the ADCs described herein to a subject does not results in non- specific accumulation of payload (cytotoxin) in the body and does not exhibit reduced delivery of the cytotoxin to the desired target cell (or the target cell microenvironment or a neighboring cell) by the anti-CDH17 antibody. In some embodiments, the anti-CDH17 ADC described herein containing SYNstatin linker-payloads exhibits enhanced potency compared to a comparable anti-CDH17 ADC, such as but not limited to an anti-CDH17 ADC containing a vedotin based linker-payload. In some embodiments, the anti-CDH17 ADC exhibits enhanced potency compared to a control isotype conjugate. In some embodiments, the enhanced potency is about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, about 5.0 fold, or higher increase in potency. 99 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, the anti-CDH17 ADC described herein containing SYNstatin linker-payloads exhibits enhanced in vitro potency compared to a comparable anti-CDH17 ADC, such as but not limited to an anti-CDH17 ADC containing a vedotin based linker- payload. In some embodiments, the anti-CDH17 ADC exhibits increased in vitro potency compared to a control isotype conjugate. In some embodiments, the enhanced in vitro potency is about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, about 5.0 fold, or higher increase in in vitro potency. In some embodiments, the anti-CDH17 ADC described herein containing SYNstatin linker-payloads exhibits increased tissue penetration compared to a comparable anti-CDH17 ADC, such as but not limited to an anti-CDH17 ADC containing a vedotin based linker- payload. In some embodiments, the anti-CDH17 ADC exhibits increased tissue penetration compared to a control isotype conjugate. In some embodiments, the increase in tissue penetration is about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, about 5.0 fold, or higher increase in tissue penetration. In some embodiments, the anti-CDH17 ADC described herein containing SYNstatin linker-payloads exhibits improved drug delivery to a target cell compared to a comparable anti-CDH17 ADC, such as but not limited to an anti-CDH17 ADC containing a vedotin based linker-payload. In some embodiments, the improved drug delivery is about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 100 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, about 5.0 fold, or higher increase in drug delivery to a target cell. In some embodiments, the anti-CDH17 ADC described herein containing SYNstatin linker-payloads exhibits reduced toxicity or nonspecific drug payload release to a subject upon administration compared to a comparable anti-CDH17 ADC, such as but not limited to an anti-CDH17 ADC containing a vedotin based linker-payload. In some embodiments, the anti-CDH17 ADC exhibits reduced toxicity or nonspecific drug payload release compared to a control isotype conjugate. In some embodiments, the improved drug delivery is about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, about 5.0 fold, or higher reduction in toxicity or nonspecific drug payload release. In some embodiments, the anti-CDH17 ADC described herein containing SYNstatin linker-payloads exhibits enhanced efficacy compared to a comparable anti-CDH17 ADC, such as but not limited to an anti-CDH17 ADC containing a vedotin based linker-payload. In some embodiments, the anti-CDH17 ADC exhibits enhanced efficacy compared to a control isotype conjugate. In some embodiments, the enhanced efficacy is about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, about 5.0 fold, or higher increase in efficacy. 101 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, the anti-CDH17 ADC described herein containing SYNstatin linker-payloads exhibits reduced toxicity compared to a comparable anti-CDH17 ADC, such as but not limited to an anti-CDH17 ADC containing a vedotin based linker-payload. In some embodiments, the anti-CDH17 ADC exhibits reduced toxicity compared to a control isotype conjugate. In some embodiments, the reduced toxicity is an about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, about 5.0 fold, or more higher reduction. In some embodiments, the anti-CDH17 ADC described herein containing SYNstatin linker-payloads exhibits increased stability in serum compared to a comparable anti-CDH17 ADC, such as but not limited to an anti-CDH17 ADC containing a vedotin based linker- payload. In some embodiments, the anti-CDH17 ADC exhibits increased serum half-life compared to a control isotype conjugate. In some embodiments, the increased stability in serum (increased serum half-life) is about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, about 5.0 fold, or higher increase. In some embodiments, the increased stability in serum is an increase in serum half-life by 1 h, 2h, 4h, 6 hr, 7h, 8h, 12h, 16h, 18h, 20h, 22 h, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, or more. In some embodiments, the anti-CDH17 ADC described herein containing SYNstatin linker-payloads exhibits improved safety compared to a comparable anti-CDH17 ADC, such as but not limited to an anti-CDH17 ADC containing a vedotin based linker-payload. In some embodiments, the anti-CDH17 ADC exhibits improved safety compared to a control isotype 102 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO conjugate. In some embodiments, the improved safety is about 1.1 fold, about 1.2 fold, about 1.3 fold, about 1.4 fold, about 1.5 fold, about 1.6 fold, about 1.7 fold, about 1.8 fold, about 1.9 fold, about 2.0 fold, about 2.1 fold, about 2.2 fold, about 2.3 fold, about 2.4 fold, about 2.5 fold, about 2.6 fold, about 2.7 fold, about 2.8 fold, about 2.9 fold, about 3.0 fold, about 3.1 fold, about 3.2 fold, about 3.3 fold, about 3.4 fold, about 3.5 fold, about 3.6 fold, about 3.7 fold, about 3.8 fold, about 3.9 fold, about 4.0 fold, about 4.1 fold, about 4.2 fold, about 4.3 fold, about 4.4 fold, about 4.5 fold, about 4.6 fold, about 4.7 fold, about 4.8 fold, about 4.9 fold, about 5.0 fold, or higher increase in safety. vi. Exemplary Embodiments of Anti-CDH17 ADCs for Inflammatory Bowel Diseases In some embodiments, a CDH17 targeting ADC includes (a) a first monomer comprising from N-terminus to C-terminus: SEQ ID NO: 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer comprising from N-terminus to C-terminus: SEQ ID NO: 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and a synthetic glucocorticoid. In some embodiments, the ADC is a DAR4 ADC. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 1-40 and 109, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 1- 40 and 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and a synthetic glucocorticoid. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C- 103 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and a synthetic glucocorticoid. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and a synthetic glucocorticoid. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of any one of SEQ ID NOS: 133-151 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of any one of SEQ ID NOS: 133-151 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and a synthetic glucocorticoid. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C- terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 104 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 133-151 and a first conjugation linker- payload attached the Fc domain of the first monomer, and (b) a second monomer from N- terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 133-151 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and a synthetic glucocorticoid. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 123 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 123 and a second conjugation linker- payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and a synthetic glucocorticoid. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 125 and a first conjugation linker- payload attached the Fc domain of the first monomer, and (b) a second monomer from N- terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 125 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and a synthetic glucocorticoid. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C- terminus comprising: an amino acid sequence of SEQ ID NO: 126 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 126 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and a synthetic glucocorticoid. 105 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, a CDH17 targeting ADC includes (a) a first monomer comprising from N-terminus to C-terminus: SEQ ID NO: 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer comprising from N-terminus to C-terminus: SEQ ID NO: 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 1-40 and 109, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 1- 40 and 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a 106 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N- terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of any one of SEQ ID NOS: 133-151 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of any one of SEQ ID NOS: 133-151 and a second conjugation linker- payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 133-151 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 133-151 and a second conjugation linker- payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an 107 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO amino acid sequence of SEQ ID NO: 123 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 123 and a second conjugation linker- payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 125 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 125 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 126 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 126 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC includes (a) a first monomer comprising from N-terminus to C-terminus: SEQ ID NO: 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer comprising from N-terminus to C-terminus: SEQ ID NO: 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 1-40 and 109, a flexible linker, and an Fc domain of human IgG, 108 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 1- 40 and 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C- terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases 109 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of any one of SEQ ID NOS: 133-151 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of any one of SEQ ID NOS: 133-151 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 133-151 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 133-151 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 123 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 123 and a second conjugation linker- payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 125 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 125 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid 110 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO sequence of SEQ ID NO: 126 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 126 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone propionate. In some embodiments, a CDH17 targeting ADC includes (a) a first monomer comprising from N-terminus to C-terminus: SEQ ID NO: 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer comprising from N-terminus to C-terminus: SEQ ID NO: 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and halobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 1-40 and 109, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 1- 40 and 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and halobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C- terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an 111 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and halobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and halobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of any one of SEQ ID NOS: 133-151 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of any one of SEQ ID NOS: 133-151 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 133-151 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or 112 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO more sequence identity to any one of SEQ ID NOS: 133-151 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and halobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 123 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 123 and a second conjugation linker- payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 125 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 125 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and halobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 126 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 126 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and halobetasol propionate. In some embodiments, a CDH17 targeting ADC includes (a) a first monomer comprising from N-terminus to C-terminus: SEQ ID NO: 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer comprising from N-terminus to C-terminus: SEQ ID NO: 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and clobetasol propionate. 113 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 1-40 and 109, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 1- 40 and 109, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and clobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and clobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG, and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or 114 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO more sequence identity to any one of SEQ ID NOS: 110-128, a flexible linker, and an Fc domain of human IgG (such as human IgG1), and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and clobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of any one of SEQ ID NOS: 133-151 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of any one of SEQ ID NOS: 133-151 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 133-151 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence having at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more sequence identity to any one of SEQ ID NOS: 133-151 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and clobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 123 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 123 and a second conjugation linker- payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker fluticasone furoate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 125 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: 115 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO an amino acid sequence of SEQ ID NO: 125 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and clobetasol propionate. In some embodiments, a CDH17 targeting ADC for use in treating inflammatory bowel diseases includes: (a) a first monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 126 and a first conjugation linker-payload attached the Fc domain of the first monomer, and (b) a second monomer from N-terminus to C-terminus comprising: an amino acid sequence of SEQ ID NO: 126 and a second conjugation linker-payload attached the Fc domain of the second monomer, wherein the first and second conjugation linker-payload each comprises a legumain cleavable linker and clobetasol propionate. VI. Method of Making Polypeptides Also provided herein are methods of producing an polypeptide that include: (a) culturing a cell (e.g., any of the cells described herein) including any of the nucleic acids encoding any of the polypeptides described herein, or any of the expression vectors described herein that include nucleic acid encoding any of the polypeptides described herein, in a culture medium under conditions sufficient to allow for the production of the polypeptide, and (b) harvesting the polypeptide from the host cell or the culture medium. In some embodiments of any of the methods described herein, the method further includes isolating the polypeptide (e.g., through performance of one or more column chromatography steps, ultrafiltration / diafiltration, and / or viral inactivation). In some embodiments of any of the methods described herein, the method further includes formulating the isolated polypeptide into a composition (e.g., a pharmaceutical composition). Any of the polypeptides described herein can be produced by any cell, e.g., a mammalian cell. Non-limiting examples of a mammalian cell include: a human cell, a rodent cell (e.g., a rat cell or a mouse cell), a rabbit cell, a dog cell, a cat cell, a porcine cell, or a non-human primate cell. For example, a host cell can be a CHO cell or a HEK cell. Methods of culturing cells are well known in the art. Cells can be maintained in vitro under conditions that favor cell proliferation, cell growth, and / or cell differentiation. For example, cells can be cultured by contacting a cell (e.g., any of the cells described herein) with a cell culture medium that includes supplemental growth factors to support cell viability and cell growth. 116 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Methods of introducing nucleic acids (e.g., any of the exemplary nucleic acids described herein) and / or expression vectors (e.g., any of the exemplary expression vectors described herein (e.g., an AAV vector)) into cells (e.g., mammalian cells) are known in the art. Non-limiting examples of methods that can be used to introduce a nucleic acid (e.g., DNA, RNA, ssRNA, siRNA, microRNA, or mRNA) and / or an expression vector (e.g., any of the exemplary expression vectors described herein (e.g., an AAV vector) include: electroporation, lipofection, transfection, microinjection, calcium phosphate transfection, dendrimer-based transfection, anionic polymer transfection, cationic polymer transfection, transfection using highly branched organic compounds, cell-squeezing, sonoporation, optical transfection, magnetofection, particle-based transfection (e.g., nanoparticle transfection), transfection using liposomes (e.g., cationic liposomes), and viral transduction (e.g., lentiviral transduction, adenoviral transduction). Some methods described herein further include isolating or purifying the polypeptide from cell culture medium or from a cell (e.g., a mammalian cell) using techniques well- known in the art (e.g., ion exchange chromatography (anionic or cation), metal-affinity chromatography, ligand-affinity chromatography, size exclusion chromatography, hydrophobic interaction chromatography, and precipitation (e.g., ammonium sulfate precipitation, polyethylene glycol precipitation). In some embodiments, anti-CDH17 ADCs described herein are produced according to any methods known to one skilled in the art. In some embodiments, a glycosylated anti- CDH17 antibody or anti-CDH17 Fc fusion protein is treated with an endoglycosidase e.g., an endo S or endo S2 enzyme or an equivalent thereof to cleave the glycan moiety to core N- acetylglycosamine (GlcNAc) residue, and the resulting core residue is coupled with a UDP- activated azidosugar via a β(1,4) linkage mediated by an N-acetylgalactosaminyltransferase from Trichoplusia ni (GalNAc-T). Next, a drug payload functionalized with a strained alkyne such as, but not limited to bicyclononyne (BCN) is conjugated to the azide group of the azidosugar in a metal-free strain-promoted azide-alkyne click chemistry (SPAAC) reaction to produce the anti-CDH17 ADCs. In some instances, the linker-drug payload conjugation to an anti-CDH17 antibody (or Fc fusion protein) is based on the N-linked glycosylation site of the IgG molecule, such as the Asn-297 (N297) side chain of the Fc domain. Additional descriptions of methods for producing an ADC can be found in, e.g., Dommerholt et al., Angew Chem Int Ed, 2010, 49,9422-9425; van Geel et al., Bioconjugate 117 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Chemistry, 2015; Verkade et al., Antibodies, 2018, 7(12); van Berkel and van Delft, Drug Discov Today: Technol, 2018; Wijdeven et al., 2022, Mabs, 2022, 14(1):2078466; and Moore et al., Xenobiotica, 2024, 54(8), 469-491. VII. Method of Treatment In some embodiments, the anti-CDH17 ADCs, Fc fusion proteins, antibodies, and antigen-domain thereof described herein may be administered to a subject for treatment of a condition. In some embodiments, the anti-CDH17 ADCs, Fc fusion proteins, antibodies, and antigen-domain thereof described herein may be administered to a subject to treat neuroendocrine tumors (NET), cholangiocarcinomas, and liver cancers (HCC) that express CDH17. Exemplary conditions may include, but not limited to, cancer, hyperplasia, neurodegenerative disease, Alzheimer's disease, cardiovascular disease, metabolic disease, vasculitis, viral infection, fungal infection, bacterial infection, diabetic retinopathy, macular degeneration, autoimmune disease, edema, pulmonary hypertension, sepsis, myocardial angiogenesis, plaque neovascularization, restenosis, neointima formation after vascular trauma, telangiectasia, hemophiliac joints, angiofibroma, fibrosis associated with chronic inflammation, lung fibrosis, deep venous thrombosis or wound granulation. In some embodiments, the anti-CDH17 antibody or antigen-binding domain thereof described herein may be of use for diagnostic or therapy of cancer. Exemplary types of cancers that may be targeted include pancreatic cancer, liver cancer, gastric cancer, lung cancer, colorectal cancer, rectal cancer, thyroid cancer, esophageal cancer, kidney cancer, bladder cancer, prostate cancer, anal cancer, cervical cancer, breast cancer, skin cancer, epithelial cancer, brain cancer, or ovarian cancer, acute lymphoblastic leukemia, acute myelogenous leukemia, biliary cancer, breast cancer, cervical cancer, chronic lymphocytic leukemia, chronic myelogenous leukemia, colorectal cancer, endometrial cancer, esophageal, gastric, head and neck cancer, Hodgkin's lymphoma, lung cancer, medullary thyroid cancer, non-Hodgkin's lymphoma, multiple myeloma, renal cancer, ovarian cancer, pancreatic cancer, glioma, melanoma, liver cancer, prostate cancer, urinary bladder cancer, and other CDH17-expressing cancers. In some embodiments, the cancer comprises a solid tumor, such as adenocarcinoma, colon adenocarcinoma, rectal adenocarcinoma, pancreatic adenocarcinoma, glioblastoma, neuroendocrine tumors, colorectal carcinoma, gastric carcinoma, esophageal carcinoma, neuroblastoma, osteosarcoma, and other CDH17- expressing tumors. In some embodiments, the subject has a metastatic cancer or a 118 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO cancer / tumor not located in the tissue or organ where the cancer was initially identified. In some embodiments, administration of the anti-CDH17 ADCs, Fc fusion proteins, antibodies, and antigen-binding domains thereof described herein to a subject (e.g., a human subject) results in tumor shrinkage or elimination. In some embodiments, administration to the subject results in an increase in overall survival compared to no such administration. In some embodiments, administration to the subject results in rapid internalization of the anti-CDH17 ADCs, Fc fusion proteins, antibodies, antigen-binding domains thereof, or any component thereof compared to the standard of care. In some embodiments, the anti-CDH17 ADCs, Fc fusion proteins, antibodies, and antigen-domain thereof described herein may be administered to a subject to treat inflammatory bowel diseases (IBDs) such as, but not limited to, Ulcerative Colitis, Crohn’s Disease, microscopic colitis, eosinophilic GI disorders (EGID), collagenous colitis, ischemic colitis, diversion colitis, indeterminate colitis, microscopic colitis, mucous colitis, pseudomembranous colitis, lymphocytic colitis, chronic inflammation of the gut lining, irritable bowel syndrome, a condition associated with impaired intestinal barrier function, an autoimmune associated condition or the gastrointestinal system. In further embodiments, the IBDs include acute IBD, severe IBD, and refractory IBD. Described herein is the pharmaceutical composition for use in a therapy includes an antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR-T therapy. In some embodiments, the pharmaceutical compositions may further comprise at least one additional therapeutic agent. In some embodiments, the subjects (e.g., human subjects) progress with cancer after receiving first line therapies including first line chemotherapies, small molecule therapies, biologic therapies, or immunotherapies. In further embodiments, the subjects are resistant or are developing resistance to second line therapies to treat cancer. VIII. Pharmaceutical Compositions Also provided herein are compositions (e.g., pharmaceutical compositions) that include any of the polypeptides, vectors, or nucleic acids described herein. Any of the pharmaceutical compositions can include any of the polypeptides, vectors, or nucleic acids described herein and one or more (e.g., 1, 2, 3, 4, or 5) pharmaceutically or physiologically acceptable carriers, diluents, or excipients. In some embodiments, any of the pharmaceutical 119 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO compositions described herein can include one or more buffers (e.g., a neutral-buffered saline, a phosphate-buffered saline (PBS)), one or more carbohydrates (e.g., glucose, mannose, sucrose, dextran, or mannitol), one or more proteins, polypeptides, or amino acids (e.g., glycine), one or more antioxidants, one or more chelating agents (e.g., glutathione or EDTA), one or more preservatives, and / or a pharmaceutically acceptable carrier (e.g., PBS, saline, or bacteriostatic water). In some embodiments, any of the pharmaceutical compositions described herein can further include one or more (e.g., 1, 2, 3, 4, or 5) agents that promote the entry of any of the vectors or nucleic acids described herein into a cell (e.g., a mammalian cell) (e.g., a liposome or cationic lipid). In some embodiments, any of the vectors or nucleic acids described herein can be formulated using natural and / or synthetic polymers. Non-limiting examples of polymers that can be included in any of the pharmaceutical compositions described herein can include, but are not limited to: poloxamer, chitosan, dendrimers and poly(lactic-co-glycolic acid) (PLGA) polymers. The pharmaceutical compositions provided herein can be, e.g., formulated to be compatible with their intended route of administration. In some embodiments, the compositions are formulated for subcutaneous, intramuscular, or intravenous administration. In some examples, the compositions include a therapeutically effective amount of any of the polypeptides, vectors, or nucleic acids described herein. Single or multiple administrations of any of the pharmaceutical compositions described herein can be given (e.g., administered) to a subject depending on, for example, the frequency and the dosage required and tolerated by the subject. A dosage of the pharmaceutical composition including any of the polypeptides described herein, any of the vectors described herein, or any of the nucleic acids described herein should provide a sufficient quantity to effectively ameliorate or treat symptoms, conditions or diseases. In some embodiments, compositions comprising antibodies can be provided in formulations with a wide variety of pharmaceutically acceptable carriers (see, e.g., Gennaro, Remington: The Science and Practice of Pharmacy with Facts and Comparisons: Drugfacts Plus, 20th ed. (2003); Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery Systems, 7th ed., Lippencott Williams and Wilkins (2004); Kibbe et al., Handbook of Pharmaceutical Excipients, 3rd ed., Pharmaceutical Press (2000)). Various pharmaceutically 120 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO acceptable carriers, which include vehicles, adjuvants, and diluents, are available. Moreover, various pharmaceutically acceptable auxiliary substances, such as pH adjusting and buffering agents, tonicity adjusting agents, stabilizers, wetting agents and the like, are also available. Non-limiting exemplary carriers include saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof. In some embodiments, compositions comprising antibodies may be formulated for injection, including subcutaneous administration, by dissolving, suspending, or emulsifying them in an aqueous or nonaqueous solvent, such as vegetable or other oils, synthetic aliphatic acid glycerides, esters of higher aliphatic acids, or propylene glycol, and if desired, with conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifying agents, stabilizers and preservatives. In various embodiments, the compositions may be formulated for inhalation, for example, using pressurized acceptable propellants such as dichlorodifluoromethane, propane, nitrogen, and the like. The compositions may also be formulated, in various embodiments, into sustained release microcapsules, such as with biodegradable or non-biodegradable polymers. A non-limiting exemplary biodegradable formulation includes poly lactic acid-glycolic acid polymer. A non-limiting exemplary non- biodegradable formulation includes a polyglycerin fatty acid ester. Certain methods of making such formulations are described, for example, in EP 1125584 A1. In some embodiments, the composition described herein may be manufactured as a medicament for treatment of cancer. In some embodiments, the composition described herein may be manufactured as a medicament for treatment of an irritable bowel disease. IX. Kits A kit comprising a pharmaceutical composition together with instructions for use is further provided. For convenience, the kit comprises reagents in predetermined amounts with instructions for use. In some embodiments, disclosed herein are kits comprising an anti-CDH17 antibody or antigen-binding domain thereof disclosed herein. In some embodiments, a kit can be a diagnostic kit. In some embodiments, a kit comprises an anti-CDH17 antibody or antigen- binding domain thereof disclosed herein and instructions for use. In some embodiments, a kit comprises means for measuring an anti-CDH17 antibody or antigen-binding domain thereof 121 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO level in a sample and instructions for use. A kit may provide a unit or device for obtaining a sample from a subject (e.g., a device with a needle coupled to an aspirator). A kit may include a plurality of syringes, ampules, foil packets, or blister packs, each containing a single unit dose of a kit component described herein. Containers of a kit may be airtight, waterproof (e.g., impermeable to changes in moistures or evaporation), and / or light- tight. A kit may include a device suitable for administration of the components, e.g., a syringe, inhalant, pipette, forceps, measured spoon, dropper (e.g., eye dropper), swab (e.g., a cotton swab or wooden swab), or any such delivery device. In some embodiments, the device may be a medical implant device, e.g., packaged for surgical insertion. A kit disclosed herein comprises one or more reagents or instruments which enable the method to be carried out. In some embodiments, reagents or instruments include one or more of the following: suitable buffer(s) (aqueous solutions), a support comprising wells on which quantitative reactions can be done. A kit may be a specific kit for a specific tissue sample. Further, a kit disclosed herein comprises a control. In some embodiments, the kit comprises any of the compositions (e.g., pharmaceutical compositions) described herein which include any of the nucleic acids, any of the polypeptides, or any of the vectors described herein. In some embodiments, a kit can include a solid composition (e.g., a lyophilized composition including any of the vectors, polypeptides, or nucleic acids described herein) and a liquid for solubilizing the lyophilized composition. In some embodiments, the kit includes a vial including any of the pharmaceutical compositions described herein (e.g., formulated as an aqueous pharmaceutical composition). EXAMPLES The application may be better understood by reference to the following non-limiting examples, which are provided as exemplary embodiments of the application. The following examples are presented in order to more fully illustrate embodiments and should in no way be construed, however, as limiting the broad scope of the application. 122 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Example 1. Potency of BHB156-SYNstatin and BHB156-vedotin in clearing tumor biomass in cell line derived xenograft (CDX) tumor-bearing mice This example describes the potency of anti-CDH17 VHH-Fc fusion protein ADCs in tumor models in NCG nice. Data shows BHB156-SYNstatin is more effective than BHB156- vedotin in the tumor models. FIG.2 shows data from the single dose study performed in a MMAE-sensitive model with descending doses to evaluate durability of responses to SYNstatin and vedotin. SYNstatin is more potent and more durable with similar responses at half the dose of the vedotin ADC. Potency of BHB156-SYNstatin (DAR4), BHB156-vedotin (DAR4) versus isotype control ADCs in clearing tumor biomass in CDX tumor-bearing mice was assessed (FIGS.1- 4). Animals were maintained under standard housing and IACUC-approved protocols. Tumor cell lines (SNU16 gastric adenocarcinoma cells, SW403 colorectal adenocarcinoma cells, AsPC1 pancreatic adenocarcinoma cells) were obtained from ATCC (Manassas, VA) and cultured according to standard protocols.5 million cells per animal were implanted in the right flank of nude mice (JAX Strain 002019) in Matrigel. Once tumor volumes reached at least 125 mm3, animals were randomized for treatment into groups of at least one animal and intravenously treated with a series of doses of BHB156-SYNstatin conjugates, BHB156- vedotin conjugates and control ADCs including isotype control-vedotin conjugates and isotype control-SYNstatin conjugates. The treatments were delivered every several days for about a total of 3 to 6 doses (see arrows in FIGS.1-4). All tumors were measured out to 42 days after randomization and treatment with electronic calipers. Data were analyzed and plotted in Prism (GraphPad). In multiple model studies with differing cell-surface CDH17 levels, BHB156-SYNstatin and BHB156-vedotin dosing led to sustained antitumor responses in gastric cancer (FIG.1), colorectal cancer (CRC) (FIG.3), and pancreatic cancer (FIG.4) models compared to comparable isotype ADC controls. BHB156-SYNstatin generated an improved antitumor response compared to BHB156-vedotin. FIG.1 shows data from the repeat dose study performed in MMAE-sensitive models with sub-therapeutic vedotin dosing (1 mg / kg q1w x3) to evaluate potency of BHB156- SYNstatin ADC. Data shows that the BHB156-SYNstatin ADC is about 2-times more potent, with similar responses at half the dose of the BHB156-vedotin ADC. 123 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO FIG.3 shows data from the repeat dose study performed in a challenging CDX models to evaluate potency of BHB156-SYNstatin ADC and BHB156-vedotin ADC. Mice were treated with a dose of 2 mg / kg. Data shows that the BHB156-SYNstatin ADC was more potent at inducing complete response than BHB156-vedotin. BHB156-SYNstatin ADC induced complete responses, while tumor outgrowth was observed in the BHB156-vedotin ADC treated tumor model animals. FIG.4 shows data from the repeat dose study performed in an extremely challenging CDX models to evaluate potency of BHB156-SYNstatin ADC and BHB156-vedotin ADC. Mice were treated with a dose of 2 mg / kg. Data shows that the BHB156-SYNstatin ADC was more potent at inducing tumor statis with significantly delayed outgrowth compared to BHB156-vedotin which had no effect. Example 2. Study design comparing safety of BHB156-SYNstatin and BHB156- vedotin This example describes a direct evaluation of BHB156-vedotin and BHB156- SYNstatin. The results showed that BHB156-SYNstatin is safer than BHB156-vedotin. BHB156-vedotin and BHB156-SYNstain were evaluated in a non-GLP rat (Sprague- Dawley, female, N=3 per group (both main tox and TK arms)) DRF study to evaluate the toxicology and toxicokinetics post multi-dose (Q1Wx3) administration of 20, 10 and 5 mg / mg IV dosing of the test articles. The study was taken down 3 days after the last dose (Day 18). Animals that survived to scheduled (Day 18) or unscheduled necropsy were evaluated for macroscopic organ findings and standard tissues collection for histopathology was performed. For animals in the main tox group that reached necropsy, blood samples were collected for clinical pathology assessments. Also, rich blood sampling after the first and third dose were collected and processed for bioanalytical analysis and TK parameter assessment. Animals in the high dose group were administered either BHB156-vedotin or BHB156-SYNstatin according to a dosing schedule of 20 mg / kg Q1Wx3. Animals in the mid dose group were administered either BHB156-vedotin or BHB156-SYNstatin according to a dosing schedule of 10 mg / kg Q1Wx3. Animals in the low dose group were administered either BHB156-vedotin or BHB156-SYNstatin according to a dosing schedule of 5 mg / kg 124 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Q1Wx3. The estimated MTDs in rat models with Q1Wx3 dosing was 5 mg / kg of BHB156- vedotin and 10 mg / kg of BHB156-SYNstatin. Example 3. Characterization of de-immunized CDH17-directed VHH-Fc variant fusion protein drug conjugates in ADC-based cytotoxicity assays The example provides comparisons of cytotoxicity of de-immunized CDH17 VHH-Fc variant fusion proteins conjugated to oYo-linked VcMMAE linker-payloads (mc-vc-PAB- MMAE; DAR2). Nineteen (19) de-immunized CDH17 VHH-Fc variants were prepared using standard oYo-Link® VcMMAE methods (AlphaThera, Philadelphia PA) to generate DAR2 ADCs. Cytotoxicity of anti-CDH17 VHH-Fc fusion protein drug bioconjugates to CDH17+ cells (SNU16 cells) was determined by an ADC cytotoxicity assay. SNU16 cells were first cultured using standard protocols.1,000 cells were seeded into each well of a standard assay well plate along with serial dilutions of each of the test ADCs or unconjugated VHH-Fc fusion protein. Cell viability was measured after 96 hours of drug exposure by the addition of equal volumes of CellTiter-Glo reagent and plate reading (SpectraMax, Molecular Devices). Cell viability measurements were normalized to a mock-treated condition and plotted in Prism (GraphPad). IC50 estimates are shown with a four-parameter sigmoid fit model. Negative control / target-independent cell killing was measured by inclusion of BHB156-Fc fusion protein drug conjugates and BHB001-Fc fusion protein drug conjugates. FIG.5 shows cytotoxicity data for BHB795-BHB800 based ADCs. FIG.6 shows cytotoxicity data for BHB801-806 based ADCs. FIG.7 shows cytotoxicity data for BHB807- BHB812 based ADCs. FIG.7 shows cytotoxicity data for a BHB813-based ADC and the control ADCs.17 of the 19 ADCs of the de-immunized CDH17 variants were either more potent or within 3-fold less potent than a parental BHB156-Fc fusion protein drug conjugate. Data suggests that the ADCs described herein are likely to be active in vivo. Example 4. Characterization of de-immunized CDH17 variant BHB810-Fc fusion proteins and corresponding drug conjugates The example describes the monovalent binding affinity, purity, and cell binding activity of a de-immunized CDH17 variant BHB810-Fc fusion protein. The example also describes the pharmacokinetics and anti-tumor activity of a BHB810-based ADC. 125 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Monovalent binding affinity of a BHB810-Fc fusion protein to His-tagged human and rat CDH17 antigens was determined using biolayer interferometry (BLI). Anti-CDH17 BHB810 antibodies were immobilized on AHC sensors and equilibrated in standard kinetics running buffer. Sensors were then exposed to various concentrations of antigen as analyte and a 1:1 Langmuir fit was subsequently applied to estimate kinetic parameters. FIG.9 shows binding to human CDH17-His as measured on BLI via AHC Ab-capture. FIG.10 shows binding to rat CDH17-His as measured on BLI via AHC Ab-capture. BHB810-Fc antibody purity was assessed by SDS-PAGE electrophoresis (FIG.11) and size exclusion chromatography (FIG.12). >99% of the sample mass migrates as a single species at the expected molecular weight for a BHB810 VHH-Fc fusion. Briefly, nucleic acid sequence encoding the BHB810-VHH-Fc fusion protein were cloned into a suitable DNA vector for secretory protein expression in mammalian systems. The constructs were transiently transfected into CHO cells, and transfected cells were cultured for 5 days under standard conditions. Expressed antibodies were isolated from crude culture supernatants by Protein A column chromatography and elution and buffer exchanged into PBS. Post- purification purity was assessed by analytical SEC-HPLC. Cell binding kinetics of BHB810-Fc antibody to CDH17+ cells (SNU16) was assessed using flow cytometry. The control antibody was a parental BHB156-Fc antibody. 100,000 SNU16 cells were seeded in each well and stained with Live / Dead Efluor450 for 30 mins at 4C. The cells were washed and incubated with the BHB810-Fc antibody for 30 mins at room temp. For the antibody exposure curve, 50nM was the top dose with a 4-fold change for a 10-point titration. The cells were washed and stained with anti-human-Alexa Fluor 647 secondary antibody according to standard protocols. Fluorescence was detected with a standard flow cytometer. Median fluorescence intensity was plotted after background subtraction and fit with a 3-parameter hill function in PRISM 10. FIG.13 shows that the de- immunized CDH17 VHH variant BHB810-Fc antibody exhibited similar binding EC50 as the parental CDH17 VHH BHB156-Fc antibody. Peripheral antibody clearance of the de-immunized CDH17 VHH variant BHB810-Fc antibody-drug bioconjugate (BHB810-SYNstatin) was assessed in non-tumor-bearing nude mice by ELISA. Animals were treated with 1 mg / kg BHB810-based ADC and peripheral whole blood was collected for plasma at various time points. ELISA plates were coated with human CDH17 overnight and subsequently blocked with 1% (w / v) BSA. Animal plasma 126 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO samples were diluted to 10% plasma + 3% (w / v) BSA and incubated in CDH17-coated wells. A standard curve was used for interpolation of experimental concentrations at each time point. Data were presented as the mean and standard deviation of three independent replicates (n = 3 mice per time point). FIG.14 shows pharmacokinetic data of the BHB810-SYNstatin ADC in non-tumor bearing nude mice. Anti-tumor activity of BHB810-SYNstatin in SNU16 tumor-bearing nude mice was assessed.6 animals per group were randomized once tumor volumes exceeded 200 mm3 and treated with 1 mg / kg isotype-SYNstatin or BHB810-SYNstatin. Body weight and tumor volumes were measured twice weekly for 4 weeks. FIG.15 shows on-target ADC induces significant anti-tumor activity. Example 5. Report for BHB810-SYNstatin The present example report summarizes the computational, in vitro, and in vivo data package supporting the candidacy of BHB810-SYNstatin for non-clinical development and first-in-human dose exploration. The example references two antibodies: BHB156 and BHB810, both can bind a human CDH17 antigen. BHB810 is a highly related sequence variant of BHB156, and BHB810 includes antibody framework mutations that reduce potential immunogenicity via mitigating predicted MHC-II epitopes. BHB156 was extensively characterized, and given that BHB810 was derived with no changes in the complementarity-determining regions (CDR) sequences, the study results are presented to support the biochemical and functional parity of BHB156 and BHB810. Where relevant, references to BHB156-specific datasets are provided, for example, for biodistribution studies. In summary, BHB810-SYNstatin is a highly developable, potent, and differentiated anti-CDH17 antibody-drug conjugate candidate. The candidate and its highly related precursor BHB156 demonstrate target engagement across human, primate, and rodent orthologues with in vitro and in vivo potency in culture-adapted and primary patient-derived models consistent with published and clinically successful ADCs in the same payload class. Moreover, the candidate is developable with excellent manufacturing properties from transient mammalian expression systems and robust stability through forced degradation systems. BHB156 has been characterized in rodent and primate models of drug metabolism and tolerability with properties consistent with previous ADC candidate therapeutics. The 127 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO studies are presented to demonstrate similar clearance and efficacy of BHB810-SYNstatin and BHB156-SYNstatin in tumor-bearing mice. Discovery The anti-CDH17 VHH was identified in “Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17 CAR T cells without toxicity to normal tissues” by Feng et al (2022, Nature Cancer, 3, 581-594). The antibody was extensively diversified from the original sequence and optimized for specific therapeutic applications. Antibody optimization Initially, sequential exploratory variants of the discovered VHH were generated and tested via large language models. After sufficient training data consisting of variant VHHs with measured true properties were accumulated, predictive models were trained on thermostability (Tm) and affinity (KD) data. These models were used to predict mutations that would further increase affinity while preserving or enhancing thermostability (Tm). In each design cycle, the top ranked variants based on predicted improved properties and model prediction uncertainty were then selected for synthesis and characterized. This process was repeated to iteratively optimize the discovered VHH into an early lead candidate. Structure-based analysis of sequence liabilities Ensembles of 100 homology structure models (all combinations of 10 CDR models and 10 framework models) were predicted for the VHHs in MOE software (chemcomp.com). A per-residue surface exposure percentage was calculated for all positions on each structure model, and values at each position were averaged across the ensemble of structures. Sequence motifs for the following liabilities were searched and evaluated based on surface exposure criteria: oxidation (Met and Trp), Asp isomerization (canonical and non-canonical), and Asn deamidation (canonical and non-canonical). The 9% threshold criteria for surface exposure was based on prior literature (Yang et al., 2017, MAbs, 9(4), 646-653). CDRs were annotated using the Kabat numbering scheme. Immunogenicity predictions Comparison to germlines and clinical stage antibodies The sequence was split into all possible 9-mers, 9-mer was chosen as the core binding peptide to MHC-II is 9 amino acids long. Each 9-mer was screened for 100% identity within the sequence of human germlines (IMGT.org) as well as marketed, under review and clinical 128 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO stage antibodies passed phase 1 clinical trials (Jain et al., 2017) with publicly available sequences. The dataset was curated to remove antibodies with known presence of anti-drug antibodies (ADA) in patients (Mosch and Guchelaar, 2022, Front Immunol, 2022 Jun 17, 13:885672) resulting in a total number of 184 antibodies. Sequence regions which were identical to either germline or this set of clinical-stage antibodies were considered “de- risked”, irrespective of their humanness or MHC-II binding predictions. MHC-II binding predictions The sequence was split into 15-mer peptides, for each peptide a binding score to each of the 27 most common MHC-II alleles in the general population (covering an estimated 98% o...

Claims

1. Attorney Docket No.55171.4008 / WO CLAIMS WHAT IS CLAIMED IS:

1. An antibody-drug conjugate comprising Formula (I):Ab-(L-D)n Formula (I), wherein: Ab binds human CDH17 and comprises an antibody or antigen-binding domain thereof comprising: (i) a humanized variant of SEQ ID NO: 109 comprising: (a) an HCDR1 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 41, (b) an HCDR2 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 47, (c) an HCDR3 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 72, and (d) a set of amino acid substitutions in framework region(s) of SEQ ID NO: 109 are selected from the group consisting of: V68I / Q74K / N83S / K85R / G90A, Q4V / T17L / S23A / F45L / Q112L, Q4V / T17L / F45L / Q112L, S59A / V68I / Q74K / N83S / K85R / G90A, Q4V / T17L / F45W / V68I / N83S / K85R / G90A / I91V, V68I / T73S / Q74K / N83S / K85R / G90A, Q4V / T17L / E42G / V68I / Q74K, V68I / N83S / K85R / G90A, Q4V / F45L, Q4V / T17L / F45W / V68I / N83S / G90A / I91V / Q112L, Q4V / T17L / E42G / K85R, Q4V / T17L / S23A / F45L, T17L / E42G / V68I / N83S / G90A, Q4V / T17L / V68I / N83S / G90A / Q112L, F45L / V68I, T17L / V68I / N83S / G90A, Q4V / F45L / Q112L, F45W / V68I / T73S / Q74K / N83S / K85R / G90A, F45W / V68I / Q74K / N83S / K85R / G90A, V68I / N83S / G90A, V68I / G90A, V68I / N83S, Q4V / T17L, Q4V, T17L, V68I, N83S, and G90A, wherein the N-terminus amino acid position of SEQ ID NO: 109 is position 0, (ii) an Fc domain; L is a sulfamide linker or a legumain-cleavable linker, wherein L is attached to an amino acid of a CH2 domain of the Fc domain; D is a cytotoxic agent or an anti-inflammatory agent; and n is a drug-to-antibody ratio (DAR), wherein the drug-to-antibody ratio is from about 1 to about 8. 142 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 2. The conjugate of claim 1, wherein the HCDR1 comprises the amino acid sequenceof SEQ ID NO: 41, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 47, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:

72.

3. The conjugate of claim 1 or 2, wherein the set of amino acid substitutions inframework region(s) are selected from the group consisting of: (a) the set of amino acid substitutions in framework 3 (FR3), (b) the set of amino acid substitutions in FR1, FR2, and FR3, (c) the set of amino acid substitutions in FR1, FR2, and FR4, (d) the set of amino acid substitutions in FR1 and FR2, (e) the set of amino acid substitutions in FR1-FR4, (f) the set of amino acid substitutions in FR1, FR3, and FR4, (g) the set of amino acid substitutions in FR2 and FR3, and (h) the set of amino acid substitutions in FR1 and FR3.

4. The conjugate of any one of claims 1-3, wherein the antibody or antigen-bindingdomain thereof comprising the set of amino acid substitutions of V68I / Q74K / N83S / K85R / G90A does not further comprise amino acid substitutions selected from the group consisting of: G71D, N78Y, T73S, F45W, S59A, G71D / N78Y, T73S / N78Y, G71D / T73S, F45W / G71D, F45W / N78Y, F45W / T73S, G71D / T73S / N78Y, F45W / G71D / N78Y, F45W / T73S / N78Y, F45W / T73D / N78Y, F45W / G71D / V77L, G71D / T73S / V77L / N78Y, G71D / T73S / V77L / P86A, G71D / V77L / N78Y / I91V, G71D / T73S / N78Y / I91V, G71D / T73S / V77L / I91V, F45W / G71D / N78Y / N78Y, F45W / G71D / V77L / N78Y, G71D / V77L / N78Y / I91V, G71D / T73S / V77L / N78Y / P86A, G71D / T73S / V77L / P86A / I91V, G71D / T73S / N78Y / P86A / I91V, G71D / V77L / N78Y / P86A / I91V, Q4V / T17L / S23A / E42G / I91V, S23A / F35V / G71D / N78Y / I91V, F45W / G71D / T73S / V77L / N78Y, T17L / R43L / F45W / G71D / V77L / I91V, Q0E / Q4V / T17L / G71D / T73A / V77L / I91V, T17L / S23A / E42G / R43L / F45W / G71D / V77L, Q0E / T17L / G71D / V77L / N78Y / S106Y / Q112L, S23A / F35V / R43L / F45W / G71D / N78Y / Q112L, Q4V / F35V / R43L / F45W / G71D / A101S / Q112L, Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / P86A, Q0E / Q4V / F35V / R43L / F45W / G71D / V77L / Q112L, Q0E / Q4V / T17S / S23A / T73A / V77L / P86A / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / P86A / Q112L, 143 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO Q0E / Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / I91V, and Q0E / Q4V / T17LS23A / G71D / T73A / V77L / N78Y / Q112L.

5. The conjugate of any one of claims 1-3, wherein the antibody or antigen-bindingdomain thereof comprising the set of amino acid substitutions of Q4V / T17L / S23A / F45L / Q112L does not further comprise amino acid substitutions selected from the group consisting of: R70L, V68I / Q74K, and V68I / Q74K / V77L / N83S / G90A.

6. The conjugate of any one of claims 1-3, wherein the antibody or antigen-bindingdomain thereof comprising the set of amino acid substitutions of Q4V / T17L / F45L / Q112L does not further comprise amino acid substitutions selected from the group consisting of: S23A, S23A / R70L, S23A / V68I / Q74K, and S23A / V68I / Q74K / V77L / N83S / G90A.

7. The conjugate of any one of claims 1-6, wherein the antibody or antigen-bindingdomain thereof comprises: an FR1 having an amino acid sequence QVQLZ1ESGGGLVQPGGSZ2RLSCVZ3SRTFSY (SEQ ID NO: 128), wherein Z1is Q or V, Z2 is T or L, and Z3 is S or A, an FR2 having an amino acid sequence WFRQAPGKZ4REZ5VA (SEQ ID NO: 129), wherein Z4is E or G, and Z5is F or L or W, an FR3 having an amino acid sequence RFTZ6SRGNZ7Z8NSVNLQMNZ9LZ10PEDTZ11Z12YYCAV (SEQ ID NO: 130), wherein Z6is V or I, Z7 is T or S, Z8 is Q or K, Z9 is N or S, Z10 is K or R, Z11 is G or A, and Z12 is I or V, and an FR4 having an amino acid sequence WGQGTZ13(SEQ ID NO: 131), wherein Z13is Q or L.

8. The conjugate of any one of claims 1-7, wherein the antibody or antigen-bindingdomain thereof comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 110-128.

9. The conjugate of any one of claims 1-8, wherein the antibody or antigen-bindingdomain thereof comprises an amino acid sequence of SEQ ID NO:

125.

10. The conjugate of any one of claims 1-8, wherein the antibody or antigen-bindingdomain thereof comprises an amino acid sequence of SEQ ID NO:

123.

11. The conjugate of any one of claims 1-8, wherein the antibody or antigen-bindingdomain thereof comprises an amino acid sequence of SEQ ID NO:

126. 144 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 12. The conjugate of any one of claims 1-11, wherein the Fc domain is derived fromIgA, IgD, IgE, IgG, or IgM.

13. The conjugate of any one of claims 1-12, wherein the Fc domain is derived fromIgG1, IgG2, or IgG4.

14. The conjugate of any one of claims 1-13, wherein the Fc domain is derived fromIgG1 or IgG4.

15. The conjugate of any one of claims 1-14, wherein the Ab is a single-domainantibody or any polypeptide comprising the humanized variant of SEQ ID NO:

109.

16. The conjugate of any one of claims 1-15, wherein the Ab comprises a VHHdomain and an Fc domain based on IgG1 or IgG4.

17. The conjugate of any one of claims 1-15, wherein the Ab comprises from N-terminus to C-terminus: a VHH domain that binds CDH17, a peptide linker, and an Fc domain based on IgG1 or IgG4.

18. The conjugate of any one of claims 1-17, wherein the Ab comprises: a firstmonomer comprising a first humanized variant of SEQ ID NO: 109 and a first Fc domain, and a second monomer comprising a second humanized variant of SEQ ID NO:109 and a second Fc domain, thereby forming a homodimeric polypeptide.

19. The conjugate of any one of claims 1-17, wherein the Ab comprises: a firstmonomer comprising a first humanized variant of SEQ ID NO: 109 and a first Fc domain, and a second monomer comprising a second humanized variant of SEQ ID NO:109 and a second Fc domain, thereby forming a heterodimeric polypeptide.

20. The conjugate of any one of claims 1-19, wherein the sulfamide linker or thelegumain-cleavable linker is attached to an asparagine at position 297 of the CH2 domain of the Fc domain.

21. The conjugate of any one of claims 1-20, wherein the sulfamide linker or thelegumain-cleavable linker comprises one or more spacer moieties and a linker moiety. 145 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 22. The conjugate of any one of claims 1-21, wherein the one or more spacer moietieseach comprises a polar sulfamide and polyethyleneglycol (PEG).

23. The conjugate of any one of claims 1-22, wherein the linker moiety comprises acleavable linker.

24. The conjugate of any one of claims 1-22, wherein the linker moiety comprises anon-cleavable linker.

25. The conjugate of claim 23, wherein the cleavable linker is a protease-cleavablelinker.

26. The conjugate of claim 25, wherein the protease-cleavable linker is a cathepsin-cleavable linker.

27. The conjugate of claim 26, wherein the cathepsin-cleavable linker is a valine-citrulline linker.

28. The conjugate of any one of claims 21-27, wherein the linker moiety furthercomprises a self-immolative spacer moiety.

29. The conjugate of claim 28, wherein the self-immolative spacer moiety is a p-aminocarbamate (PABC) spacer moiety.

30. The conjugate of any one of claims 1-29, wherein the cytotoxic agent is selectedfrom the group consisting of: toxin targeting ribosome, toxin targeting elongation factor, toxin targeting tubulin, toxin targeting DNA, toxin targeting RNA, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine (PBD) dimer, benzodiazepine, CC-1065 analogue, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracyl (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analog, DX-8951f, exatecan mesylate, duocarmycin derivative, amanitin, a-amanitin, spliceostatin, a thailanstatin, ozogamicin, Amberstatin269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), Monomethyl Auristatin D (MMAD), monomethyl dolastatin 10, Monomethyl Auristatin F (MMAF, mafodotin), N-methylvaline-valine- dolaisoleuine-dolaproine-phenylalanine, Monomethyl Auristatin E (MMAE), N- 146 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO methylvaline-valine-dolaisoleuine-dolaproine-norephedrine, deruxtecan, tesirine, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, histone deacetylase inhibitors, PE38, SN-38, ENPP3, tubulysin, exatecan, STING agonist, TLR agonist, alpha-amanitin, SGD-1882, CC- 1065, and 5-benzoylvaleric acid-AE ester (AEVB).

31. The conjugate of any one of claims 1-30, wherein the cytotoxic agent is MMAE.

32. The conjugate of any one of claims 1-29, wherein the anti-inflammatory agent isselected from the group consisting of: synthetic glucocorticoid, glucocorticoid analog, fluticasone furoate (FF), fluticasone propionate (FP), halobetasol propionate, clobetasol propionate, glucocorticoid receptor modulator (GRM), and any derivatives thereof.

33. The conjugate of any one of claims 1-32, wherein the sulfamide linker furthercomprises one or more attachment groups.

34. The conjugate of claim 33, wherein the one or more attachment groups is selectedfrom the group consisting of maleimide, caproic acid, and both.

35. The conjugate of any one of claims 1-34, wherein n is about 4.

36. The conjugate of any one of claims 1-35, wherein the conjugate exhibits increasedserum half-life compared to a control isotype conjugate.

37. The conjugate of any one of claims 1-36, wherein the conjugate exhibits increasedtissue penetration compared to a control isotype conjugate.

38. The conjugate of any one of claims 1-37, wherein the conjugate exhibits increasedin vitro potency compared to a control isotype conjugate.

39. The conjugate of any one of claims 1-38, wherein the conjugate exhibits improveddrug delivery to a target cell compared to a control isotype conjugate.

40. The conjugate of any one of claims 1-39, wherein the conjugate exhibits reducedtoxicity or nonspecific payload release to a subject upon administration as compared to a control isotype conjugate. 147 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 41. The conjugate of any one of claims 1-40, wherein the conjugate exhibits increasedin vivo potency or efficacy to a subject upon administration as compared to a control isotype conjugate.

42. The conjugate of any one of claims 36-41, wherein the control isotype conjugateis a vedotin antibody-drug conjugate.

43. An anti-CDH17 Fc fusion protein comprising:(i) a humanized variant of SEQ ID NO: 109 comprising: (a) an HCDR1 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 41, (b) an HCDR2 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 47, (c) an HCDR3 having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 72, and (d) a set of amino acid substitutions in framework region(s) of SEQ ID NO: 109 are selected from the group consisting of: V68I / Q74K / N83S / K85R / G90A, Q4V / T17L / S23A / F45L / Q112L, Q4V / T17L / F45L / Q112L, S59A / V68I / Q74K / N83S / K85R / G90A, Q4V / T17L / F45W / V68I / N83S / K85R / G90A / I91V, V68I / T73S / Q74K / N83S / K85R / G90A, Q4V / T17L / E42G / V68I / Q74K, V68I / N83S / K85R / G90A, Q4V / F45L, Q4V / T17L / F45W / V68I / N83S / G90A / I91V / Q112L, Q4V / T17L / E42G / K85R, Q4V / T17L / S23A / F45L, T17L / E42G / V68I / N83S / G90A, Q4V / T17L / V68I / N83S / G90A / Q112L, F45L / V68I, T17L / V68I / N83S / G90A, Q4V / F45L / Q112L, F45W / V68I / T73S / Q74K / N83S / K85R / G90A, F45W / V68I / Q74K / N83S / K85R / G90A, V68I / N83S / G90A, V68I / G90A, V68I / N83S, Q4V / T17L, Q4V, T17L, V68I. N83S, and G90A, wherein the N-terminus amino acid position of SEQ ID NO: 109 is position 0, and (ii) an Fc domain.

44. The anti-CDH17 Fc fusion protein of claim 43, wherein the HCDR1 comprisesthe amino acid sequence of SEQ ID NO: 41, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 47, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:

72.

45. The anti-CDH17 Fc fusion protein of claim 43 or 44, wherein the set of aminoacid substitutions in framework region(s) are selected from the group consisting of: (a) the set of amino acid substitutions in framework 3 (FR3), (b) the set of amino acid substitutions in FR1, FR2, and FR3, (c) the set of amino acid substitutions in FR1, FR2, and FR4, (d) the set 148 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO of amino acid substitutions in FR1 and FR2, (e) the set of amino acid substitutions in FR1- FR4, (f) the set of amino acid substitutions in FR1, FR3, and FR4, (g) the set of amino acid substitutions in FR2 and FR3, and (h) the set of amino acid substitutions in FR1 and FR3.

46. The anti-CDH17 Fc fusion protein of any one of claims 43-45, wherein the set ofamino acid substitutions in framework region(s) comprising V68I / Q74K / N83S / K85R / G90A does not further comprise amino acid substitutions selected from the group consisting of: G71D, N78Y, T73S, F45W, S59A, G71D / N78Y, T73S / N78Y, G71D / T73S, F45W / G71D, F45W / N78Y, F45W / T73S, G71D / T73S / N78Y, F45W / G71D / N78Y, F45W / T73S / N78Y, F45W / T73D / N78Y, F45W / G71D / V77L, G71D / T73S / V77L / N78Y, G71D / T73S / V77L / P86A, G71D / V77L / N78Y / I91V, G71D / T73S / N78Y / I91V, G71D / T73S / V77L / I91V, F45W / G71D / N78Y / N78Y, F45W / G71D / V77L / N78Y, G71D / V77L / N78Y / I91V, G71D / T73S / V77L / N78Y / P86A, G71D / T73S / V77L / P86A / I91V, G71D / T73S / N78Y / P86A / I91V, G71D / V77L / N78Y / P86A / I91V, Q4V / T17L / S23A / E42G / I91V, S23A / F35V / G71D / N78Y / I91V, F45W / G71D / T73S / V77L / N78Y, T17L / R43L / F45W / G71D / V77L / I91V, Q0E / Q4V / T17L / G71D / T73A / V77L / I91V, T17L / S23A / E42G / R43L / F45W / G71D / V77L, Q0E / T17L / G71D / V77L / N78Y / S106Y / Q112L, S23A / F35V / R43L / F45W / G71D / N78Y / Q112L, Q4V / F35V / R43L / F45W / G71D / A101S / Q112L, Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / P86A, Q0E / Q4V / F35V / R43L / F45W / G71D / V77L / Q112L, Q0E / Q4V / T17S / S23A / T73A / V77L / P86A / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / I91V / Q112L, Q4V / T17L / S23A / G71D / T73S / V77L / N78Y / P86A / Q112L, Q0E / Q4V / T17L / S23A / G71D / T73A / V77L / N78Y / I91V, and Q0E / Q4V / T17LS23A / G71D / T73A / V77L / N78Y / Q112L.

47. The anti-CDH17 Fc fusion protein of any one of claims 43-45, wherein the set ofamino acid substitutions in framework region(s) comprising Q4V / T17L / S23A / F45L / Q112L does not further comprise amino acid substitutions selected from the group consisting of: R70L, V68I / Q74K, and V68I / Q74K / V77L / N83S / G90A. 149 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 48. The anti-CDH17 Fc fusion protein of any one of claims 43-45, wherein the set ofamino acid substitutions in framework region(s) comprising Q4V / T17L / F45L / Q112L does not further comprise amino acid substitutions selected from the group consisting of: S23A, S23A / R70L, S23A / V68I / Q74K, and S23A / V68I / Q74K / V77L / N83S / G90A.

49. The anti-CDH17 Fc fusion protein of any one of claims 43-48, wherein the set ofamino acid substitutions in framework region(s) comprises: an FR1 having an amino acid sequence QVQLZ1ESGGGLVQPGGSZ2RLSCVZ3SRTFSY (SEQ ID NO: 128), wherein Z1is Q or V, Z2 is T or L, and Z3 is S or A, an FR2 having an amino acid sequence WFRQAPGKZ4REZ5VA (SEQ ID NO: 129), wherein Z4 is E or G, and Z5 is F or L or W, an FR3 having an amino acid sequence RFTZ6SRGNZ7Z8NSVNLQMNZ9LZ10PEDTZ11Z12YYCAV (SEQ ID NO: 130), wherein Z6 is V or I, Z7is T or S, Z8is Q or K, Z9is N or S, Z10is K or R, Z11is G or A, and Z12is I or V, and an FR4 having an amino acid sequence WGQGTZ13 (SEQ ID NO: 131), wherein Z13 is Q or L.

50. The anti-CDH17 Fc fusion protein of any one of claims 43-49, comprising anamino acid sequence selected from the group consisting of SEQ ID NOS: 110-128.

51. The anti-CDH17 Fc fusion protein of any one of claims 43-50, comprising anamino acid sequence of SEQ ID NO:

125.

52. The anti-CDH17 Fc fusion protein of any one of claims 43-50, comprising anamino acid sequence of SEQ ID NO:

123.

53. The anti-CDH17 Fc fusion protein of any one of claims 43-50, comprising anamino acid sequence of SEQ ID NO:

126.

54. The anti-CDH17 Fc fusion protein of any one of claims 43-53, wherein the Fcdomain is derived from IgA, IgD, IgE, IgG, or IgM.

55. The anti-CDH17 Fc fusion protein of any one of claims 43-54, wherein the Fcdomain is derived from IgG1, IgG2, or IgG4.

56. The anti-CDH17 Fc fusion protein of any one of claims 43-55, wherein the Fcdomain is derived from IgG1 or IgG4. 150 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 57. The anti-CDH17 Fc fusion protein of any one of claims 43-56, comprising a VHHdomain comprising the humanized variant of SEQ ID NO: 109, and the Fc domain comprises an Fc domain based on IgG1 or IgG4.

58. The anti-CDH17 Fc fusion protein of any one of claims 43-57, comprising fromN-terminus to C-terminus: a VHH domain comprising the humanized variant of SEQ ID NO: 109, a peptide linker, and the Fc domain comprises an Fc domain based on IgG1 or IgG4.

59. The anti-CDH17 Fc fusion protein of any one of claims 43-58, comprising anyone of SEQ ID NOS: 145, 147, and 148.

60. The anti-CDH17 Fc fusion protein of any one of claims 43-59, comprising SEQID NO:

147.

61. The anti-CDH17 Fc fusion protein of any one of claims 43-59, comprising SEQID NO:

145.

62. The anti-CDH17 Fc fusion protein of any one of claims 43-59, comprising SEQID NO:

148.

63. The anti-CDH17 Fc fusion protein of any one of claims 43-62, comprising: a firstmonomer from N-terminus to C-terminus comprising a first humanized variant of SEQ ID NO: 109 and a first Fc domain of human IgG, and a second monomer from N-terminus to C- terminus comprising a second humanized variant of SEQ ID NO:109 and a second Fc domain of human IgG, thereby forming a homodimeric polypeptide.

64. The anti-CDH17 Fc fusion protein of any one of claims 43-62, comprising: a firstmonomer from N-terminus to C-terminus comprising a first humanized variant of SEQ ID NO: 109 and a first Fc domain of human IgG, and a second monomer from N-terminus to C- terminus comprising a second humanized variant of SEQ ID NO:109 and a second Fc domain of human IgG, thereby forming a heterodimeric polypeptide.

65. The anti-CDH17 Fc fusion protein of claim 63 or 64, wherein the first monomercomprises any one of SEQ ID NOS: 132-150, and the second monomer comprises any one of SEQ ID NOS: 132-150. 151 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 66. The anti-CDH17 Fc fusion protein of any one of claims 63-65, wherein the firstmonomer comprises SEQ ID NOS: 145, 147, and 148, and the second monomer comprises SEQ ID NOS: 145, 147, and 148.

67. The anti-CDH17 Fc fusion protein of any one of claims 63-65, wherein the firstmonomer comprises SEQ ID NO: 147, and the second monomer comprises SEQ ID NO:

147.

68. The anti-CDH17 Fc fusion protein of any one of claims 63-65, wherein the firstmonomer comprises SEQ ID NO: 145, and the second monomer comprises SEQ ID NO:

145.

69. The anti-CDH17 Fc fusion protein of any one of claims 63-65, wherein the firstmonomer comprises SEQ ID NO: 148, and the second monomer comprises SEQ ID NO:

148.

70. An anti-CDH17 antibody-drug conjugate comprising Formula (I):Ab-(L-D)n Formula (I), wherein: Ab binds human CDH17 and comprises from the N-terminus to C-terminus: a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72 and a set of amino acid substitutions of V68I / Q74K / N83S / K85R / G90A in framework region 3, wherein the N- terminus amino acid position of SEQ ID NO: 109 is position 0; a linker of SEQ ID NO: 101; and an Fc domain of human IgG1; L comprises a polar sulfamide polyethyleneglycol chain connected to Val-Cit-p- aminobenzyloxycarbonyl (vc-PABC), wherein L is attached to the N297 of the CH2 domain of the Fc domain; D is MMAE; and n is 4.

71. An anti-CDH17 antibody-drug conjugate comprising Formula (I):Ab-(L-D)n Formula (I), wherein: Ab binds human CDH17 and comprises from the N-terminus to C-terminus: a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72 and a set of amino acid substitutions of Q4V / T17L / S23A / F45L / Q112L in framework regions 1, 2, and 4, wherein the N-terminus amino acid position of SEQ ID NO: 109 is position 0; a linker of SEQ ID NO: 101; and an Fc domain of human IgG1; 152 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO L comprises a polar sulfamide polyethyleneglycol chain connected to Val-Cit-p- aminobenzyloxycarbonyl (vc-PABC), wherein L is attached to the N297 of the CH2 domain of the Fc domain; D is MMAE; and n is 4.

72. An anti-CDH17 antibody-drug conjugate comprising Formula (I):Ab-(L-D)n Formula (I), wherein: Ab binds human CDH17 and comprises from the N-terminus to C-terminus: a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72 and a set of amino acid substitutions of Q4V / T17L / F45L / Q112L in framework regions 1, 2, and 4, wherein the N- terminus amino acid position of SEQ ID NO: 109 is position 0; a linker of SEQ ID NO: 101; and an Fc domain of human IgG1; L comprises a polar sulfamide polyethyleneglycol chain connected to Val-Cit-p- aminobenzyloxycarbonyl (vc-PABC), wherein L is attached to the N297 of the CH2 domain of the Fc domain; D is MMAE; and n is 4.

73. An anti-CDH17 Fc fusion protein comprising from the N-terminus to C-terminus:(a) a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72, and a set of amino acid substitutions of V68I / Q74K / N83S / K85R / G90A in framework region 3, wherein the N- terminus amino acid position of SEQ ID NO: 109 is position 0; (b) a linker of SEQ ID NO: 101; and (c) an Fc domain of human IgG1; wherein the anti-CDH17 Fc fusion protein binds human CDH17.

74. An anti-CDH17 Fc fusion protein comprising from the N-terminus to C-terminus:(a) a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72, and a set of amino acid substitutions of Q4V / T17L / S23A / F45L / Q112L in framework regions 1, 2, and 4, wherein the N-terminus amino acid position of SEQ ID NO: 109 is position 0; 153 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO (b) a linker of SEQ ID NO: 101; and (c) an Fc domain of human IgG1; wherein the anti-CDH17 Fc fusion protein binds human CDH17.

75. An anti-CDH17 Fc fusion protein comprising from the N-terminus to C-terminus:(a) a humanized variant of SEQ ID NO: 109 comprising an HCDR1 of SEQ ID NO: 41 an HCDR2 of SEQ ID NO: 47 an HCDR3 of SEQ ID NO: 72, and a set of amino acid substitutions of Q4V / T17L / F45L / Q112L in framework regions 1, 2, and 4, wherein the N- terminus amino acid position of SEQ ID NO: 109 is position 0; (b) a linker of SEQ ID NO: 101; and (c) an Fc domain of human IgG1; wherein the anti-CDH17 Fc fusion protein binds human CDH17.

76. An anti-CDH17 Fc fusion protein comprising an amino acid sequence of SEQ IDNO:

147.

77. An anti-CDH17 Fc fusion protein comprising two monomers each comprising anamino acid sequence of SEQ ID NO:

147.

78. An anti-CDH17 Fc fusion protein comprising an amino acid sequence of SEQ IDNO:

148.

79. An anti-CDH17 Fc fusion protein comprising two monomers each comprising anamino acid sequence of SEQ ID NO:

148.

80. An anti-CDH17 Fc fusion protein comprising an amino acid sequence of SEQ IDNO:

145.

81. An anti-CDH17 Fc fusion protein comprising two monomers each comprising anamino acid sequence of SEQ ID NO:

145.

82. An anti-CDH17 VHH antigen binding domain comprising an amino acid sequenceof SEQ ID NO:

125.

83. An anti-CDH17 VHH antigen binding domain comprising an amino acid sequenceof SEQ ID NO:

126. 154 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 84. An anti-CDH17 VHH antigen binding domain comprising an amino acidsequence of SEQ ID NO:

123.

85. One or more nucleic acids encoding the anti-CDH17 antibody-drug conjugate ofany one of claims 1-42 and 70-72, the anti-CDH17 Fc fusion protein of any one of claims 43- 69 and 73-81, or the anti-CDH17 VHH antigen binding domain of any one of claims 82-84.

86. An expression vector comprising the one or more nucleic acids of claim 85.

87. A host cell comprising the one or more nucleic acids of claim 85 or the expressionvector of claim 86.

88. A method of producing an anti-CDH17 antibody-drug conjugate, an anti-CDH17Fc fusion protein, or an anti-CDH17 VHH antigen binding domain, comprising: (a) maintaining the host cell of claim 87 in a medium to produce cancer, (b) isolating the anti- CDH17 antibody-drug conjugate, the anti-CDH17 Fc fusion protein, or the anti-CDH17 VHH antigen binding domain produced by the host cell, and optionally (c) purifying the anti- CDH17 antibody-drug conjugate, the anti-CDH17 Fc fusion protein, or the anti-CDH17 VHH antigen binding domain.

89. A pharmaceutical composition for treating cancer comprising the anti-CDH17antibody-drug conjugate of any one of claims 1-42 and 70-72, the anti-CDH17 Fc fusion protein of any one of claims 43-69 and 73-81, or the anti-CDH17 VHH antigen binding domain of any one of claims 82-84, and a pharmaceutically acceptable carrier or excipient.

90. The pharmaceutical composition of claim 89, further comprising at least oneadditional therapeutic agent.

91. The pharmaceutical composition of claim 90, wherein the at least one additionaltherapeutic agent comprises T cell-engaging immunotherapy, CAR-T therapy, or a small molecule therapy.

92. A kit comprising (a) the anti-CDH17 antibody-drug conjugate of any one ofclaims 1-42 and 70-72, the anti-CDH17 Fc fusion protein of any one of claims 43-69 and 73- 81, or the anti-CDH17 VHH antigen binding domain of any one of claims 82-84, and (b) instructions for use. 155 4166-0318-6015.4 Attorney Docket No.55171.4008 / WO 93. A method for treating cancer comprising administering to a human subject withcancer the anti-CDH17 antibody-drug conjugate of any one of claims 1-42 and 70-72, the anti-CDH17 Fc fusion protein of any one of claims 43-69 and 73-81, the anti-CDH17 VHH antigen binding domain of any one of claims 82-84, or the pharmaceutical composition of any one of claims 89-91.

94. The method of claim 93, wherein the cancer is selected from the group consistingof CDH17-positive cancer, gastrointestinal cancer, pancreatic cancer, neuroendocrine cancer, liver cancer, and colorectal cancer.

95. A method for treating an inflammatory bowel disease comprising administering toa human subject the anti-CDH17 antibody-drug conjugate of any one of claims 1-42 and 70- 72, the anti-CDH17 Fc fusion protein of any one of claims 43-69 and 73-81, or the anti- CDH17 VHH antigen binding domain of any one of claims 82-84, or the pharmaceutical composition of any one of claims 89-91.

96. The method of claim 95, wherein the inflammatory bowel disease is selected fromthe group consisting of Ulcerative Colitis, Crohn’s Disease, microscopic colitis, and eosinophilic GI disorder. 156 4166-0318-6015.4

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