Anti-CDH17 antibodies and uses thereof

Abstract

Anti-CDH17 antibodies and uses thereof are described herein. The anti-CDH17 antibodies provided herein exhibit significantly improved binding affinity after optimization.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 442,389, filed January 31, 2023, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] Antibody-driven targeted cancer immunotherapy plays a major role in cancer immunotherapy. Antibodies have demonstrated efficacy in targeting and killing tumor cells by targeting surface antigens expressed on tumor cells. Summary of the Invention

[0003] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41; (b) an HCDR2 having an amino acid sequence set forth in any one of SEQ ID NOs: 43-60; and (c) an HCDR3 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 61-75.

[0004] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41; (b) an HCDR2 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 42-60; and (c) an HCDR3 having the amino acid sequence set forth in any one of SEQ ID NOs: 62-75.

[0005] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 43, and / or an HCDR3 set forth in SEQ ID NO: 62.

[0006] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 44, and / or an HCDR3 set forth in SEQ ID NO: 63.

[0007] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 43, and / or an HCDR3 set forth in SEQ ID NO: 64.

[0008] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 45, and / or an HCDR3 set forth in SEQ ID NO: 65.

[0009] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 46, and / or an HCDR3 set forth in SEQ ID NO: 65. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6.

[0010] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 47, and / or an HCDR3 set forth in SEQ ID NO: 72.

[0011] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 46, and / or an HCDR3 set forth in SEQ ID NO: 65.

[0012] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising at least one amino acid substitution at positions 25 to 106 in the amino acid sequence set forth in SEQ ID NO:1.

[0013] Provided herein is an anti-CDH17 antibody, or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWRGX2NAEYX3DX4VX5G (SEQ ID NO: 79), where X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L.

[0014] Provided herein is an anti-CDH17 antibody, or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GNNAEYX3DX4VX5G (SEQ ID NO: 81), where X1 is N or R, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L.

[0015] Provided herein is an anti-CDH17 antibody, or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYRDX4VX5G (SEQ ID NO: 82), where X1 is N or R, X2 is E or N, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L.

[0016] Provided herein is an anti-CDH17 antibody, or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is D or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L.

[0017] Provided herein is an anti-CDH17 antibody, or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VHG (SEQ ID NO: 84), where X1 is N or R, X2 is E or N, X3 is S or R, and X4 is S, D, or F; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L.

[0018] Provided herein is an anti-CDH17 antibody, or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TYGX7AX8SVRX9 (SEQ ID NO: 85), where X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L.

[0019] Provided herein is an anti-CDH17 antibody, or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is T, V, K, or N, X8 is R or K, and X9 is S or L.

[0020] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AKSVRX9 (SEQ ID NO: 86), where 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 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1.

[0021] Provided herein is an anti-CDH17 antibody, or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRL (SEQ ID NO: 87), where X6 is H or Y, X7 is G, T, V, K, or N, and X8 is R or K.

[0022] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) the amino acid sequence LLDWX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A).

[0023] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WRGX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A).

[0024] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A).

[0025] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 YX 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A).

[0026] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 SEYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A).

[0027] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is R or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A).

[0028] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 EX 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A).

[0029] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A).

[0030] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X17 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A).

[0031] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TYGX 20 AX 21 SVRX22 HCDR3 (wherein X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A).

[0032] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A).

[0033] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AKSVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 22 is S, L, K, or A).

[0034] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is L, K, or A).

[0035] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, wherein the anti-CDH17 antibody or antigen-binding fragment thereof has increased binding affinity to CDH17 compared to the binding affinity to CDH17 of the amino acid sequence set forth in SEQ ID NO:1.

[0036] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, wherein the anti-CDH17 antibody or antigen-binding fragment thereof has increased stability compared to the stability of the amino acid sequence set forth in SEQ ID NO:1.

[0037] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, wherein the anti-CDH17 antibody or antigen-binding fragment thereof has a higher purity compared to the purity of the amino acid sequence set forth in SEQ ID NO:1.

[0038] Provided herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.

[0039] Provided herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof conjugated to a cytotoxic agent and / or an Fc domain.

[0040] Provided herein is a conjugate comprising the formula (I): Ab-(LD)n, wherein Ab comprises an anti-CDH17 antibody or antigen-binding fragment thereof, wherein the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41, (b) an HCDR2 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) an HCDR3 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 61-75; L is a linker; D is a cytotoxic agent; and n is a drug-antibody ratio, wherein the drug-antibody ratio is from about 1 to about 8.

[0041] Provided herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein described herein, a protein disclosed herein, or a conjugate described herein.

[0042] Provided herein are expression vectors comprising a nucleic acid encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein, a multispecific binding molecule disclosed herein, or a protein disclosed herein.

[0043] Provided herein are host cells comprising a nucleic acid or expression vector encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein, a multispecific binding molecule disclosed herein, or a protein disclosed herein.

[0044] Provided herein are methods for producing an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein, a multispecific binding molecule disclosed herein, or a protein disclosed herein, the method comprising maintaining a host cell in culture to produce the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, or protein, and isolating or purifying the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, or protein produced by the host cell.

[0045] Provided herein is a pharmaceutical composition for treating cancer comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein, a specific binding molecule disclosed herein, a protein disclosed herein, a nucleic acid disclosed herein, an expression vector or host cell disclosed herein, and a pharmaceutically acceptable carrier or excipient.

[0046] Provided herein are methods for treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein, a multispecific binding molecule disclosed herein, a protein disclosed herein, a nucleic acid disclosed herein, an expression vector disclosed herein, a host cell disclosed herein, or a pharmaceutical composition disclosed herein.

[0047] Provided herein is the use of an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein, a multispecific binding molecule disclosed herein, a protein disclosed herein, a nucleic acid disclosed herein, an expression vector disclosed herein, a host cell disclosed herein, or a pharmaceutical composition disclosed herein in the manufacture of a medicament for the treatment of cancer.

[0048] Provided herein is a kit comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein, a multispecific binding molecule disclosed herein, a protein disclosed herein, a nucleic acid disclosed herein, an expression vector disclosed herein, a host cell disclosed herein, or a pharmaceutical composition disclosed herein, and instructions for use.

[0049] Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are 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 herein.

[0050] 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 disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings. [Brief explanation of the drawings]

[0051] [Figure 1] Figure 1 shows an exemplary multispecific T cell engager design illustrating possible arrangements of VHH and scFv or Fab. [Figure 2] An exemplary bispecific T cell engager construct lacking the Fc domain (1+1 geometry) can be produced in CHO cells with high purity, as shown by SEC-HPLC. [Figure 3] We demonstrate by SEC-HPLC that an exemplary asymmetric bispecific T cell engager construct with an Fc domain (2+1 geometry) can be produced with high purity in CHO cells. [Figure 4] We demonstrate by SEC-HPLC that an exemplary symmetric bispecific T cell engager construct with an Fc domain (2+2 geometry) can be produced with high purity in CHO cells. [Figure 5] We show that exemplary bispecific T cell engager constructs readily induce T cell-dependent cellular cytotoxicity (TDCC) in co-cultures of primary human T cells and AsPC-1 pancreatic adenocarcinoma cells (10:1 T cell:target cell ratio). [Figure 6] It is shown by SEC-HPLC that VHH-Fc fusion proteins can be produced with high purity in CHO cells. [Figure 7] The VHH-Fc fusion protein can be readily conjugated to a cytotoxic linker payload (e.g., vc-PAB-MMAE) via interchain disulfide bond reduction and maleimide chemistry, demonstrating an average DAR of 2.0 and high post-conjugation purity by SEC-HPLC. [Figure 8] We show that CDH17 VHH-Fc fusion proteins conjugated to mc-vc-PAB-MMAE induce potent cytotoxicity against representative CDH17+ cancer cell lines in vitro with a low pM IC50. Unconjugated CDH17-directed VHH-Fc fusions are not cytotoxic. [Figure 9] Figure 1 shows a comparison of the cytotoxicity of CDH17-VHH-0156-Fc (SEQ ID NO: 108) and the parental VHH-0001-Fc fusion protein (SEQ ID NO: 107) mc-vc-PAB-MMAE conjugate (DAR2) in SNU16 cells. [Figure 10] CDH17 expression in primary tumor biopsy core samples assessed by immunohistochemistry (IHC) is shown. [Figure 11] Representative in vitro cancer cell drug sensitivity plots for BHB156-vedotin (DAR4) against a representative CDH17+ cancer cell line (A) and primary patient-derived xenograft (PDX) cancer cell tissue (B) are shown. [Figure 12]A summary table of receptor density measurements by antibody binding capacity (ABC) of CDH17 molecules per cell surface is shown, along with cell line sensitivity by IC50 estimates derived from serial dilutions of in vitro BHB156-Vedotin (DAR4) or isotype control Vedotin ADC. [Figure 13] A summary table of receptor density measurements by antibody binding capacity (ABC) of CDH17 molecules per cell surface and IHC scores is shown, along with cell line sensitivity by IC50 estimates derived from serial dilutions of in vitro BHB156-vedotin (DAR4) or isotype control vedotin ADC. [Figure 14] Representative plots and summary tables of plasma elimination of a single dose of varying concentrations of I-125 radiolabeled BHB156 or anti-SARS-CoV-2 isotype control VHH-Fc fusion protein in Sprague-Dawley rats are shown. [Figure 15] Representative biodistribution from a single dose of 20 mg / kg I-125 radiolabeled BHB156 or anti-SARS-CoV-2 isotype control VHH-Fc fusion protein in Sprague-Dawley rats assessed 3 or 10 days after administration of BHB156 or isotype control VHH-Fc. [Figure 16A] Shows the efficacy of BHB156 vedotin (DAR4) vs isotype vedotin in eliminating tumor burden in cell line-derived xenograft (CDX) tumor-bearing mice. [Figure 16B] Shows the efficacy of BHB156 vedotin (DAR4) vs isotype vedotin in eliminating tumor burden in cell line-derived xenograft (CDX) tumor-bearing mice. [Figure 16C] Shows the efficacy of BHB156 vedotin (DAR4) vs isotype vedotin in eliminating tumor burden in cell line-derived xenograft (CDX) tumor-bearing mice. [Figure 16D] Shows the efficacy of BHB156 vedotin (DAR4) vs isotype vedotin in eliminating tumor burden in cell line-derived xenograft (CDX) tumor-bearing mice. DETAILED DESCRIPTION OF THE INVENTION

[0052] overview In some embodiments, described herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising at least one genetic modification, wherein the at least one genetic modification results in a substantial improvement in binding affinity and increased inhibition of CDH17 activity. In some embodiments, the anti-CDH17 antibody can comprise at least one genetic modification that results in the substitution, deletion, or insertion of at least one amino acid in the polypeptide encoding the anti-CDH17 or antigen-binding fragment thereof.

[0053] In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof provided herein can be Fab fragments, Fab' fragments, Fab'-SH fragments, F(ab')2 fragments, Fv fragments, TaFv fragments, scFv fragments, diabody fragments, bsDb fragments, scDb fragments, DART fragments, BiTE fragments, and VHH fragments. For example, the anti-CDH17 antibodies or antigen-binding fragments thereof described herein can be multispecific antigen-binding proteins (e.g., bispecific T cell-engaging antibodies) that bind to an antigen of interest (e.g., a protein) with sufficient affinity and do not significantly cross-react with other proteins so that they can be used as diagnostic and / or therapeutic agents in targeting the protein or cells, tissues, or tumors that express the protein. The present disclosure can be a bispecific antibody (BsAb) capable of binding to both CD3 and CDH17.

[0054] In some embodiments, the anti-CDH17 antibodies provided herein can comprise an anti-CDH17 antibody or fragments and portions thereof (e.g., a cytotoxic agent, an Fc domain). For example, the anti-CDH17 antibody or fragment thereof composition can be an anti-CDH17 antibody or antigen-binding fragment thereof conjugated to a cytotoxic agent and / or an Fc domain via a linker (L). Also described herein are methods for treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-CDH17 antibody or antigen-binding fragment thereof composition.

[0055] Anti-CDH17 immunotherapy may hold significant promise as a treatment for a number of hematological and solid tissue malignancies. Recognized herein is an unmet need for engineering anti-CDH17 antibody compositions with enhanced binding affinity to CDH17. Disclosed herein are methods for engineering anti-CDH17 antibody compositions with enhanced binding affinity to CDH17.

[0056] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising: (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) an HCDR2 having the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) an HCDR3 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 61-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises at least one of: (a) an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, (b) an HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) an HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (scFv), a single-chain antibody, a Fab fragment, a F(ab')2 fragment, a Fd fragment, an Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising the anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (flu orouracyl) (5-FU), mitoxantrone, indolinobenzodiazepines, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracyclines, camptothecin analogues, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicehostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), Auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N -acetyl-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, and the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is used in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0057] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising: (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) an HCDR2 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 42-60, and (c) an HCDR3 having the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises at least one of: (a) an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, (b) an HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) an HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (scFv), a single-chain antibody, a Fab fragment, a F(ab')2 fragment, a Fd fragment, an Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising the anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0058] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 43, and / or an HCDR3 set forth in SEQ ID NO: 62. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0059] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 44, and / or an HCDR3 set forth in SEQ ID NO: 63. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 3. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0060] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 43, and / or an HCDR3 set forth in SEQ ID NO: 64. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 4. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0061] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 45, and / or an HCDR3 set forth in SEQ ID NO: 65. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 5. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0062] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 46, and / or an HCDR3 set forth in SEQ ID NO: 65. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0063] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 47, and / or an HCDR3 set forth in SEQ ID NO: 72. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having an amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0064] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 46, and / or an HCDR3 set forth in SEQ ID NO: 65. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0065] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof, comprising at least one amino acid substitution at positions 25-106 in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the at least one amino acid substitution comprises at least 2, 3, 4, 5, 6, or 7 amino acid substitutions. In some embodiments, the at least one amino acid substitution comprises a substitution of an amino acid with I, Y, D, R, N, S, A, E, T, F, H, V, L, or K. In some embodiments, the at least one amino acid substitution comprises 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 fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having an amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0066] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWRGX2NAEYX3DX4VX5G (SEQ ID NO: 79), where X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody.In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0067] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GNNAEYX3DX4VX5G (SEQ ID NO: 81), where X1 is N or R, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody.In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0068] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYRDX4VX5G (SEQ ID NO: 82), where X1 is N or R, X2 is E or N, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (scFv), a single-chain antibody, a Fab fragment, a F(ab')2 fragment, a Fd fragment, an Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody.In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0069] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is D or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (scFv), a single-chain antibody, a Fab fragment, a F(ab')2 fragment, a Fd fragment, an Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0070] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VHG (SEQ ID NO: 84), where X1 is N or R, X2 is E or N, X3 is S or R, and X4 is S, D, or F; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody.In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0071] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TYGX7AX8SVRX9 (SEQ ID NO: 85), where X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (scFv), a single-chain antibody, a Fab fragment, a F(ab')2 fragment, a Fd fragment, an Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody.In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0072] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (scFv), a single-chain antibody, a Fab fragment, a F(ab')2 fragment, a Fd fragment, an Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0073] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AKSVRX9 (SEQ ID NO: 86), where 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 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (scFv), a single-chain antibody, a Fab fragment, a F(ab')2 fragment, a Fd fragment, an Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody.In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0074] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRL (SEQ ID NO: 87), where X6 is H or Y, X7 is G, T, V, K, or N, and X8 is R or K. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (scFv), a single-chain antibody, a Fab fragment, a F(ab')2 fragment, a Fd fragment, an Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody.In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0075] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) the amino acid sequence LLDWX 11GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0076] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10WRGX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0077] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0078] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10WX 11 GX 12 YX 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0079] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10WX 11 GX 12 X 13 SEYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0080] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is R or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0081] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 EX 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0082] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0083] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0084] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TYGX 20 AX 21 SVRX 22 HCDR3 (wherein X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0085] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0086] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AKSVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof.Disclosed herein are proteins comprising the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein conjugated to a cytotoxic agent and / or Fc domain. In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, or 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl and α-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).In some embodiments, nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0087] (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 and 109. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0088] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof having increased binding affinity to CDH17 compared to the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding fragment thereof to CDH17 is at least three-fold higher than the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding fragment thereof to CDH17 is at least five-fold higher than the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding fragment thereof to CDH17 is at least ten-fold higher than the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the binding affinity of the anti-CDH17 antibody or antigen-binding fragment thereof to CDH17 is at least 15-fold higher than the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has a saturation of 1.0 x 10 for binding to CDH17. -8 In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has a KD of less than 5.0 x 10 for binding to CDH17. -9 In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has a KD of less than 3.0 x 10 for binding to CDH17. -9 In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has a KD of less than 1.0 x 10 -9 IC less than M 50 In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof inhibits CDH17 activity at 100.0 x 10 -12 IC less than M 50 In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof inhibits CDH17 activity at 50.0 x 10 -12 IC less than M 50In some embodiments, the IC of an anti-CDH17 antibody or antigen-binding fragment thereof to CDH17 is 50 is the IC of the amino acid sequence shown in SEQ ID NO: 1 to CDH17 50 In some embodiments, the IC of an anti-CDH17 antibody or antigen-binding fragment thereof to CDH17 is at least 10-fold lower than 50 is the IC of the amino acid sequence shown in SEQ ID NO: 1 to CDH17 50In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) an HCDR2 having an amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) an HCDR3 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 61-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) an HCDR2 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 42-60, and (c) an HCDR3 having the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises at least one of (a) an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, (b) an HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) an HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 43, and / or an HCDR3 set forth in SEQ ID NO: 62. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO:41, an HCDR2 set forth in SEQ ID NO:44, and / or an HCDR3 set forth in SEQ ID NO:63. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:3. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO:41, an HCDR2 set forth in SEQ ID NO:43, and / or an HCDR3 set forth in SEQ ID NO:64. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:4. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO:41, an HCDR2 set forth in SEQ ID NO:45, and / or an HCDR3 set forth in SEQ ID NO:65. The anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:5. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 46, and / or an HCDR3 set forth in SEQ ID NO: 65. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises at least one amino acid substitution at positions 25-106 in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the at least one amino acid substitution comprises at least 2, 3, 4, 5, 6, or 7 amino acid substitutions. In some embodiments, the at least one amino acid substitution comprises substitution of an amino acid with I, Y, D, R, N, S, A, E, T, F, H, V, L, or K.In some embodiments, the at least one amino acid substitution comprises 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 fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWRGX2NAEYX3DX4VX5G (SEQ ID NO: 79), wherein X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GNNAEYX3DX4VX5G (SEQ ID NO: 81), wherein X1 is N or R, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYRDX4VX5G (SEQ ID NO: 82), wherein X1 is N or R, X2 is E or N, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is D or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VHG (SEQ ID NO: 84), where X1 is N or R, X2 is E or N, X3 is S or R, and X4 is S, D, or F; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83). X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L; and (c) an HCDR3 having the amino acid sequence TYGX7AX8SVRX9 (SEQ ID NO: 85), wherein X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), wherein X6 is H or Y, X7 is T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence 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 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRL (SEQ ID NO: 87), where X6 is H or Y, X7 is G, T, V, K, or N, and X8 is R or K. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) the amino acid sequence LLDWX. 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WRGX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is N, I, or Y, and X 13 is N or Y, and X 14is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 YX 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 SEYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14is A or S, and X 15 is R or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 EX 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 94) HCDR2 (in the sequence, X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TYGX 20 AX 21 SVRX 22 HCDR3 (wherein X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AKSVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising the anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. The anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T-cell engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0089] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof having increased stability compared to the stability of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the stability of the anti-CDH17 antibody or antigen-binding fragment thereof to CDH17 is measured by melting temperature (Tm). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has a Tm of less than 70°C. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has a Tm of less than 60°C. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has a Tm of less than 50°C. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) an HCDR2 having the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) an HCDR3 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 61-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) an HCDR2 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 42-60, and (c) an HCDR3 having the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises at least one of (a) an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, (b) an HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) an HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 43, and / or an HCDR3 set forth in SEQ ID NO: 62. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 44, and / or an HCDR3 set forth in SEQ ID NO: 63. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 3. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 43, and / or an HCDR3 set forth in SEQ ID NO: 64. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 4. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 45, and / or an HCDR3 set forth in SEQ ID NO: 65. The anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 5. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 46, and / or an HCDR3 set forth in SEQ ID NO: 65. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises at least one amino acid substitution at positions 25-106 in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the at least one amino acid substitution comprises at least 2, 3, 4, 5, 6, or 7 amino acid substitutions. In some embodiments, the at least one amino acid substitution comprises a substitution of an amino acid with I, Y, D, R, N, S, A, E, T, F, H, V, L, or K. In some embodiments, the at least one amino acid substitution comprises 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 fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWRGX2NAEYX3DX4VX5G (SEQ ID NO: 79), wherein X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GNNAEYX3DX4VX5G (SEQ ID NO: 81), wherein X1 is N or R, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYRDX4VX5G (SEQ ID NO: 82), wherein X1 is N or R, X2 is E or N, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is D or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VHG (SEQ ID NO: 84), wherein X1 is N or R, X2 is E or N, X3 is S or R, and X4 is S, D, or F; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TYGX7AX8SVRX9 (SEQ ID NO: 85), wherein X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), wherein X6 is H or Y, X7 is T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is S, D, or F. is M or H); and (c) an HCDR3 having the amino acid sequence TX6GX7AKSVRX9 (SEQ ID NO: 86), where 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 antibody or antigen-binding fragment thereof comprises (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRL (SEQ ID NO: 87), where X6 is H or Y, X7 is G, T, V, K, or N, and X8 is R or K. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WRGX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12is N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 YX 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 SEYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14is A or S, and X 15 is R or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 EX 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 S, L, K, and or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR1 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TYGX 20 AX 21 SVRX 22 HCDR3 (wherein X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AKSVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising the anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell comprises an expression vector or nucleic acid disclosed herein. In some embodiments, a pharmaceutical composition comprises an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, or a host cell, and a pharmaceutically acceptable carrier or excipient. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, an expression vector, a host cell, a method, or a pharmaceutical composition is for use in therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, expression vector, host cell, method, or pharmaceutical composition is for use in therapy, where the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell-engaging immunotherapy, or CAR T therapy. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for use in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, conjugate, nucleic acid, expression vector, host cell, or pharmaceutical composition is for the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

[0090] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof having a higher purity compared to the purity of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have a purity greater than 96%. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have a purity greater than 97%. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have a purity greater than 98%. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have a purity greater than 99%. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have a purity of 100%. 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 fragment thereof comprises (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) an HCDR2 having an amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) an HCDR3 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 61-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) an HCDR2 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 42-60, and (c) an HCDR3 having the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises at least one of: (a) an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41; (b) an HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60; and (c) an HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-75.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 43, and / or an HCDR3 set forth in SEQ ID NO: 62. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO: 41, an HCDR2 set forth in SEQ ID NO: 44, and / or an HCDR3 set forth in SEQ ID NO: 63. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 3. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO:41, an HCDR2 set forth in SEQ ID NO:43, and / or an HCDR3 set forth in SEQ ID NO:64. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:4. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO:41, an HCDR2 set forth in SEQ ID NO:45, and / or an HCDR3 set forth in SEQ ID NO:65. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises an HCDR1 set forth in SEQ ID NO:41, an HCDR2 set forth in SEQ ID NO:46, and / or an HCDR3 set forth in SEQ ID NO:65.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises at least one amino acid substitution at positions 25-106 in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the at least one amino acid substitution comprises at least 2, 3, 4, 5, 6, or 7 amino acid substitutions. In some embodiments, the at least one amino acid substitution comprises substitution of an amino acid with I, Y, D, R, N, S, A, E, T, F, H, V, L, or K. In some embodiments, the at least one amino acid substitution comprises 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 fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWRGX2NAEYX3DX4VX5G (SEQ ID NO: 79), wherein X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GNNAEYX3DX4VX5G (SEQ ID NO: 81), wherein X1 is N or R, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYRDX4VX5G (SEQ ID NO: 82), wherein X1 is N or R, X2 is E or N, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is D or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VHG (SEQ ID NO: 84), wherein X1 is N or R, X2 is E or N, X3 is S or R, and X4 is S, D, or F; and (c) an HCDR3 having the amino acid sequence 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 X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TYGX7AX8SVRX9 (SEQ ID NO: 85), wherein X7 is G, T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRX9 (SEQ ID NO: 80), where X6 is H or Y, X7 is T, V, K, or N, X8 is R or K, and X9 is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H. X6GX7AKSVRX9 (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 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), where X1 is N or R, X2 is E or N, X3 is S or R, X4 is S, D, or F, and X5 is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRL (SEQ ID NO: 87), where X6 is H or Y, X7 is G, T, V, K, or N, and X8 is R or K. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLDWX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WRGX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 YX 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 SEYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is R or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 EX 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (Distribution HCDR3 (in the sequence, X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TYGX 20 AX 21 SVRX 22 HCDR3 (wherein X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is T, V, K, or N, and X 21 is R or K, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AKSVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 22 is S, L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR2 (wherein X 10 is S or D, and X 11 is N or R, and X 12 is E, N, I, or Y, and X 13 is N or Y, and X 14 is A or S, and X 15 is S, R, or A, and X 16 is D or E, and X 17 is S, D, F, or T, and X 18 is M or H); and (c) the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 (wherein X 19 is H or Y, and X 20 is G, T, V, K, or N, and X 21 is R or K, and X 22is L, K, or A). In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises Q37Y, A38Y, R52I, and / or T67V in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is 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 Fv (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 consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is an scFv antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is humanized. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a non-human antibody. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, disclosed herein are multispecific binding molecules comprising a first binding domain and a second binding domain, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, disclosed herein are proteins comprising the anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain.In some embodiments, the cytotoxic agent is a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil. (5-FU), mitoxantrone, indolinobenzodiazepine, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracycline, camptothecin analogue, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, Amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastin 10, monomethyl auristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoleiin-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl Antibodies include α-γ-calicheamicin, maytansinoids, pyrrolobenzodiazepines (PBDs), doxorubicin, anthracyclines, camptothecin derivatives, taxanes, hedgehog inhibitors, nitrogen mustards, and histone deacetylase inhibitors, PE38, SN-38, ENPP3, tublysin, exatecan, STING agonists, TLR agonists, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). Disclosed herein are nucleic acids encoding the anti-CDH17 antibodies or antigen-binding fragments thereof disclosed herein.In some embodiments, nucleic acids encoding the multispecific binding molecules disclosed herein are disclosed herein. In some embodiments, nucleic acids encoding the proteins disclosed herein are disclosed herein. In some embodiments, the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA. In some embodiments, an expression vector comprises a nucleic acid disclosed herein. In some embodiments, a host cell...

Claims

1. An anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41; (b) an HCDR2 having an amino acid sequence set forth in any one of SEQ ID NOs: 43-60; and (c) an HCDR3 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 61-75.

2. An anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41; (b) an HCDR2 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 42-60; and (c) an HCDR3 having the amino acid sequence set forth in any one of SEQ ID NOs: 62-75.

3. The anti-CDH17 antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the anti-CDH17 antibody or antigen-binding fragment thereof comprises at least one of: (a) an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41; (b) an HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43 to 60; and (c) an HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62 to 75.

4. (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) the amino acid sequence LLSWRGX ２ NAEYX ３ DX ４ VX ５ HCDR2 (wherein X ２ is E or N, and X ３ is S or R, and X ４ is S, D, or F, and X ５ is M or H); and (c) the amino acid sequence TX ６ GX ７ AX ８ SVRX ９ HCDR3 having (SEQ ID NO: 80) ６ is H or Y, and X ７ is G, T, V, K, or N, and X ８ is R or K, and X ９ is S or L).

5. X ２ is N and X ３ is S and X ４ is S and X ５ is M and X ６ is Y and X ７ is G and X ８ is R and X ９ The anti-CDH17 antibody or antigen-binding fragment thereof according to claim 4, wherein

6. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, wherein the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2 to 40 or 109.

7. An anti-CDH17 antibody or antigen-binding fragment thereof, comprising HCDR1 shown in SEQ ID NO: 41, HCDR2 shown in SEQ ID NO: 47, and / or HCDR3 shown in SEQ ID NO:

72.

8. The anti-CDH17 antibody or antigen-binding fragment thereof of claim 7, wherein the anti-CDH17 antibody or antigen-binding fragment thereof comprises the amino acid sequence set forth in SEQ ID NO:

109.

9. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 8, wherein the anti-CDH17 antibody or antigen-binding fragment thereof has increased binding affinity to CDH17 compared to the binding affinity to CDH17 of the amino acid sequence shown in SEQ ID NO:

1.

10. 10. The anti-CDH17 antibody or antigen-binding fragment thereof of claim 9, wherein the binding affinity of the anti-CDH17 antibody or antigen-binding fragment thereof to CDH17 is at least 3-fold, at least 5-fold, at least 10-fold, or at least 15-fold higher than the binding affinity of the amino acid sequence shown in SEQ ID NO: 1 to CDH17.

11. The anti-CDH17 antibody or antigen-binding fragment thereof has a binding affinity of 1.0 x 10 －８ Less than M, 5.0 x 10 －９ Less than M or 3.0 x 10 －９ The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 10, having a KD of less than M.

12. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 11, wherein the anti-CDH17 antibody or antigen-binding fragment thereof has increased stability compared to the stability of the amino acid sequence shown in SEQ ID NO: 1, and the stability of the anti-CDH17 antibody or antigen-binding fragment thereof to CDH17 is measured by melting temperature (Tm).

13. 13. The anti-CDH17 antibody or antigen-binding fragment thereof of claim 12, wherein the anti-CDH17 antibody or antigen-binding fragment thereof has a Tm of less than 70°C, less than 60°C, or less than 50°C.

14. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 13, wherein the anti-CDH17 antibody or antigen-binding fragment thereof has a higher purity compared to the purity of the amino acid sequence shown in SEQ ID NO:

1.

15. 15. The anti-CDH17 antibody or antigen-binding fragment thereof of claim 14, wherein the anti-CDH17 antibody or antigen-binding fragment thereof has a purity of 96%, 97%, 98%, 99%, or 100%.

16. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 15, wherein the anti-CDH17 antibody or antigen-binding fragment thereof is a monoclonal antibody, a polyclonal antibody, a bispecific antibody, a multispecific antibody, a graft antibody, a human antibody, a humanized antibody, a synthetic antibody, a chimeric antibody, a camelized antibody, a single-chain Fv (scFv), a single-chain antibody, a Fab fragment, an F(ab')2 fragment, an Fd fragment, an Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only the variable domain of a single monomer, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotype (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof.

17. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, wherein the anti-CDH17 antibody or antigen-binding fragment thereof is a VHH antibody.

18. The anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1 to 17, wherein the anti-CDH17 antibody or antigen-binding fragment thereof is humanized.

19. The anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 18, wherein the anti-CDH17 antibody or antigen-binding fragment thereof is a human antibody.

20. Formula (I): Ab-(L-D)n Formula (I) wherein Ab comprises an anti-CDH17 antibody or antigen-binding fragment thereof, wherein the anti-CDH17 antibody or antigen-binding fragment thereof comprises (a) an HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:41, (b) an HCDR2 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs:43-60, and (c) an HCDR3 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs:61-75; L is a linker; D is a cytotoxic agent; n is a drug-antibody ratio, and said drug-antibody ratio is from about 1 to about 8; The conjugate.

21. 21. The conjugate of claim 20, wherein the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HCDR1 having the amino acid sequence set forth in SEQ ID NO: 41; (b) an HCDR2 having the amino acid sequence set forth in SEQ ID NO: 47; and (c) an HCDR3 having the amino acid sequence set forth in SEQ ID NO:

72.

22. 22. The conjugate of claim 20 or 21, wherein the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2-40 or 109.

23. The conjugate of any one of claims 20 to 22, wherein the anti-CDH17 antibody or antigen-binding fragment thereof comprises an amino acid sequence having the amino acid sequence set forth in SEQ ID NO:

109.

24. The conjugate of any one of claims 20 to 23, wherein the anti-CDH17 antibody or antigen-binding fragment thereof further comprises an Fc domain.

25. 25. The conjugate of claim 24, wherein the Fc domain is derived from IgA, IgD, IgE, IgG, or IgM.

26. The cytotoxic agent may be a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, pasudotox, maytansinoid derivative DM1, maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine, a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, Indolinobenzodiazepines, AZ13599185, cryptophycin, rhizoxin, methotrexate, anthracyclines, camptothecin analogues, DX-8951f, exatecan mesylate, duocarmycin derivatives, amanitin, splicostatin, tylanstatin, ozogamicin, amberstatin 269, soravtansine, dolastin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin Monomethyldolastin D (MMAD), monomethyldolastin 10, monomethylauristatin F (MMAF, mafodotin), N-methylvaline-valine-dolaisoloiin-dolaproine-phenylalanine, monomethylauristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoloiin-dolaproine-norephedrine, deruxtecan, tesirin, mertansine, ravtansine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoids, pyrophosphate 26. The conjugate of any one of claims 20 to 25, comprising a benzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a hedgehog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tublysin, exatecan, a STING agonist, a TLR agonist, α-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).

27. 27. The conjugate of claim 26, wherein the cytotoxic agent is MMAE.

28. The conjugate of any one of claims 20 to 27, wherein the linker comprises a bond, a cleavable linker, and / or a non-cleavable linker.

29. The conjugate of any one of claims 20 to 28, wherein the linker comprises a linking group, a protease-cleavable linker, and / or a spacer.

30. 30. The conjugate of claim 29, wherein the linking group comprises maleimide and / or caproic acid.

31. 31. The conjugate of claim 29 or 30, wherein the protease-cleavable linker is a cathepsin-cleavable linker.

32. 32. The conjugate of claim 31, wherein the cathepsin-cleavable linker is a valine-citrulline linker.

33. The conjugate of any one of claims 20 to 32, further comprising a spacer.

34. 34. The conjugate of claim 33, wherein the spacer is PABC.

35. The conjugate of any one of claims 20 to 34, wherein n is about 4.

36. A nucleic acid encoding the anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1 to 20, or the conjugate of any one of claims 20 to 35.

37. 37. The nucleic acid of claim 36, wherein the nucleic acid comprises DNA, RNA, ssRNA, siRNA, microRNA, or mRNA.

38. 38. An expression vector comprising the nucleic acid of claim 36 or 37.

39. 39. A host cell comprising a nucleic acid according to claim 36 or 37 or an expression vector according to claim 38.

40. 39. A method for producing the anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1 to 19, or the conjugate of any one of claims 20 to 35, comprising maintaining the host cell of claim 39 in a culture medium to produce the anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1 to 19, or the conjugate of any one of claims 20 to 35, and isolating or purifying the anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1 to 19, or the conjugate of any one of claims 20 to 35 produced by the host cell.

41. 40. A pharmaceutical composition for treating cancer, comprising the anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1 to 19, the conjugate of any one of claims 20 to 35, the nucleic acid of claim 36 or 37, the expression vector of claim 38, or the host cell of claim 39, and a pharmaceutically acceptable carrier or excipient.

42. 42. The pharmaceutical composition of claim 41, wherein the pharmaceutical composition further comprises at least one additional therapeutic agent.

43. 41. The anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1 to 19, the conjugate of any one of claims 20 to 35, the nucleic acid of claim 36 or 37, the expression vector of claim 38, the host cell of claim 39, the method of claim 40, or the pharmaceutical composition of claim 41 or 42, for use in therapy.

44. 43. The anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1 to 19, the conjugate of any one of claims 20 to 35, the nucleic acid of claim 36 or 37, the expression vector of claim 38, the host cell of claim 39, the method of claim 40, or the pharmaceutical composition of claim 41 or 42, wherein the therapy is antibody monotherapy, antibody drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR T therapy.

45. 39. A method for treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1 to 19, the conjugate of any one of claims 20 to 35, the nucleic acid of claim 36 or 37, the expression vector of claim 38, the host cell of claim 39, or the pharmaceutical composition of claim 41 or 42.

46. Use of the anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1 to 19, the conjugate of any one of claims 20 to 35, the nucleic acid of claim 36 or 37, the expression vector of claim 38, the host cell of claim 39, or the pharmaceutical composition of claim 41 or 42 in the manufacture of a medicament for the treatment of cancer.

47. 47. The use of claim 46, wherein the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

48. Use of the anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 19, the conjugate according to any one of claims 20 to 35, the nucleic acid according to claim 36 or 37, the expression vector according to claim 38, the host cell according to claim 39, or the pharmaceutical composition according to claim 41 or 42 for the diagnosis of cancer.

49. 49. The use of claim 48, wherein the cancer is gastric cancer, pancreatic cancer, neuroendocrine cancer, or colorectal cancer.

50. 42. A kit comprising an anti-CDH17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 19, a conjugate according to any one of claims 20 to 35, a nucleic acid according to claim 36 or 37, an expression vector according to claim 38, a host cell according to claim 39, or a pharmaceutical composition according to claim 41 or 42, and instructions for use.

Images