Anti-CDH17 antibodies and uses thereof

Abstract

Anti-CDH17 antibodies and uses thereof are described herein. The anti-CDH17 antibody provided by the invention shows a remarkably improved binding affinity after being optimized.

Description

[0001] Cross Reference To Related Applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 442,389, filed January 31, 2023, which is incorporated by reference herein in its entirety. BACKGROUND

[0003] Antibody-driven targeted cancer immunotherapy has played an important role in cancer immunotherapy. By targeting surface antigens expressed on tumor cells, antibodies have shown efficacy in targeting and killing tumor cells. SUMMARY

[0004] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) a HCDR2 having the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a HCDR3 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 61-75.

[0005] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) a 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) a HCDR3 having the amino acid sequence set forth in any one of SEQ ID NOs: 62-75.

[0006] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 43, and / or a HCDR3 set forth in SEQ ID NO: 62.

[0007] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 44, and / or a HCDR3 set forth in SEQ ID NO: 63.

[0008] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 43, and / or a HCDR3 set forth in SEQ ID NO: 64.

[0009] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 45, and / or a HCDR3 set forth in SEQ ID NO: 65.

[0010] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 46, and / or a HCDR3 set forth in SEQ ID NO: 65. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6.

[0011] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 47, and / or a HCDR3 set forth in SEQ ID NO: 72.

[0012] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 46, and / or a HCDR3 set forth in SEQ ID NO: 65.

[0013] 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.

[0014] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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.

[0015] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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.

[0016] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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.

[0017] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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 D or F, and X5 is M or H; and (c) a 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.

[0018] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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.

[0019] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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.

[0020] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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.

[0021] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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 T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1.

[0022] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a HCDR3 having the amino acid sequence TX6GX7AX8SVRL (SEQ ID NO: 87), wherein X6 is H or Y, X7 is G, T, V, K, or N, and X8 is R or K.

[0023] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLDWX 11 GX 12X13X 14 EYX 15 X 16 X 17 VX 18 G(SEQ ID NO:88) HCDR2, where X 11 For N or R, X 12 For E, N, I, or Y, X 13 For N or Y, X 14 For A or S, X 15 For S, R, or A, X 16 For D or E, X 17 It is S, D, F or T, and X 18 (M) or (H); and (c) having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 of (SEQ ID NO:89), where X 19 For H or Y, X 20 For G, T, V, K, or N, X 21 It is R or K, and X 22 It can be S, L, K or A.

[0024] This document provides an anti-CDH17 antibody or its antigen-binding fragment thereof, wherein the anti-CDH17 antibody or its antigen-binding fragment comprises: (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO:41); and (b) having the amino acid sequence LLX. 10 WRGX 12 X13X 14 EYX 15 X 16 X 17 VX 18 G(SEQ ID NO:90) of HCDR2, where X 10 For S or D, X 12 For E, N, I, or Y, X 13 For N or Y, X 14 For A or S, X 15 For S, R, or A, X 16 For D or E, X 17 It is S, D, F or T, and X 18 (M) or (H); and (c) having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 of (SEQ ID NO:89), where X 19 For H or Y, X 20 For G, T, V, K, or N, X21 is S, L, K, or A. 22 is S, L, K, or A.

[0025] Provided herein are anti-CDH17 antibodies, or antigen-binding fragments thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 91), wherein X 10 is S or D, X 11 is N or R, X 12 is E, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HC DR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A.

[0026] Provided herein are anti-CDH17 antibodies, or antigen-binding fragments thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 YX 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 92), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 14is S, R or A, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) has the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 of SEQ ID NO: 89, wherein X 19 is H or Y, X 20 is G, T, V, K or N, X 21 is R or K, and X 22 is S, L, K or A.

[0027] Provided herein are anti-CDH17 antibodies, or antigen-binding fragments thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX12X 13 SEYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 93) wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I or Y, X 13 is N or Y, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) has the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 of SEQ ID NO: 89, wherein X 19 is H or Y, X 20 is G, T, V, K or N, X 21 is R or K, and X 22 is S, L, K or A.

[0028] Provided herein are anti-CDH17 antibodies, or antigen-binding fragments thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX11 GX12X 13 X 14 EYX 15 X 16 X 17 VX 18 G(SEQ ID NO:94) HCDR2, where X 10 For S or D, X 11 For N or R, X 12 For E, N, I, or Y, X 13 For N or Y, X 14 For A or S, X 15 For R or A, X 16 For D or E, X 17 It is S, D, F or T, and X 18 (M) or (H); and (c) having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HC DR3 of (SEQ ID NO:89), wherein X 19 For H or Y, X 20 For G, T, V, K, or N, X 21 It is R or K, and X 22 It can be S, L, K or A.

[0029] This document provides an anti-CDH17 antibody or its antigen-binding fragment thereof, wherein the anti-CDH17 antibody or its antigen-binding fragment comprises: (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO:41); and (b) having the amino acid sequence LLX. 10 WX 11 GX12X 13 X 14 EYX 15 EX 17 VX 18 G(SEQ ID NO:95) of HCDR2, where X 10 For S or D, X 11 For N or R, X 12 For E, N, I, or Y, X 13 For N or Y, X 14 For A or S, X 15 For S, R, or A, X 17 It is S, D, F or T, and X 18 (M) or (H); and (c) having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 of (SEQ ID NO:89), where X19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A.

[0030] Provided herein are anti-CDH17 antibodies, or antigen-binding fragments thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 94), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 96), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A.

[0031] Provided herein are anti-CDH17 antibodies, or antigen-binding fragments thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X 17 VHG (SEQ ID NO: 97), wherein X 10 is S or D, X 11 is N or R, X12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T; and (c) has the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 of (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A.

[0032] Provided herein are anti-CDH17 antibodies, or antigen-binding fragments thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 94), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has the amino acid sequence TYGX 20 AX 21 SVRX 22 HCDR3 of (SEQ ID NO: 98), wherein X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A.

[0033] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X 17 VX 18 G(SEQ ID NO: 94), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A.

[0034] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X 17 VX 18 G(SEQ ID NO: 94), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X17 is S, D, F, or T, and X 18 is M or H; and (c) has the amino acid sequence TX 19 GX 20 AKSVRX 22 (SEQ ID NO: 99) HC DR3, wherein X 19 is H or Y, X 20 is G, T, V, K, or N, and X 22 is S, L, K, or A.

[0035] Provided herein are anti-CDH17 antibodies, or antigen-binding fragments thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 94) HC DR3, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) HC DR3, wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is L, K, or A.

[0036] Provided herein are anti-CDH17 antibodies, or antigen-binding fragments thereof, having an increased binding affinity for CDH17 compared to the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1 for CDH17.

[0037] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof, wherein the anti-CDH17 antibodies or antigen-binding fragments thereof have increased stability compared to the stability of the amino acid sequence set forth in SEQ ID NO: 1.

[0038] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof, wherein the anti-CDH17 antibodies or antigen-binding fragments thereof have higher purity compared to the purity of the amino acid sequence set forth in SEQ ID NO: 1.

[0039] 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.

[0040] Provided herein are proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof conjugated to a cytotoxic agent and / or an Fc domain.

[0041] Provided herein are conjugates comprising Formula (I): Ab-(L-D)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) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41, (b) a 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) a 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 to antibody ratio, wherein the drug to antibody ratio is about 1 to about 8.

[0042] Provided herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule described herein, a protein disclosed herein, or a conjugate described herein.

[0043] 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.

[0044] 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.

[0045] Provided herein are methods of producing an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein, a multispecific binding molecule disclosed herein, or a protein disclosed herein, the methods comprising maintaining a host cell in culture to produce the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein, and isolating or purifying the anti-CDH17 antibody or antigen-binding fragment thereof, multispecific binding molecule, protein produced by the host cell.

[0046] Provided herein are pharmaceutical compositions 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 disclosed herein, or a host cell disclosed herein, and a pharmaceutically acceptable carrier or excipient.

[0047] 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.

[0048] Provided herein are uses 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 treating cancer.

[0049] Provided herein are kits 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.

[0050] incorporated by reference

[0051] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF DRAWINGS

[0052] The novel features of the application are set forth with particularity in the claims that follow. 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 present disclosure are utilized, and the accompanying drawings of which:

[0053] Figures 1A-1CExemplary multispecific T cell engager designs showing possible arrangements of VHH and scFv or Fab are shown.

[0054] Figure 2 Exemplary bispecific T cell engaging constructs lacking Fc domain (1+1 geometry) that can be produced in CHO cells are shown with high purity as determined by SEC-HPLC.

[0055] Figure 3 Exemplary bispecific T cell engaging constructs with Fc domain (2+1 geometry) that can be produced in CHO cells are shown with high purity as determined by SEC-HPLC.

[0056] Figure 4 Exemplary bispecific T cell engaging constructs with Fc domain (2+2 geometry) that can be produced in CHO cells are shown with high purity as determined by SEC-HPLC.

[0057] Figure 5 Exemplary bispecific T cell engaging constructs readily induce T cell dependent cellular cytotoxicity (TDCC) in co-culture of primary human T cells and AsPC-1 pancreatic adenocarcinoma cells (10: 1 T cell: target cell ratio) are shown.

[0058] Figure 6 VHH-Fc fusion proteins that can be produced in CHO cells are shown with high purity as determined by SEC-HPLC.

[0059] Figure 7 VHH-Fc fusion proteins can be readily conjugated to a cytotoxic linker payload (e.g., vc-PAB-MMAE) with an average DAR of 2.0 and with high post-conjugation purity as determined by SEC-HPLC through reduction of interchain disulfide bonds and maleimide chemistry are shown.

[0060] Figure 8 CDH17 VHH-Fc fusion proteins conjugated to mc-vc-PAB-MMAE induce potent cytotoxicity against representative CDH17+ cancer cell lines in vitro with IC 50 as low as pM. Unconjugated CDH17 directed VHH-Fc fusions are not cytotoxic.

[0061] Figure 9 Cytotoxicity comparison of CDH17-VHH-0156-Fc (SEQ ID NO: 108) and parental VHH-0001-Fc fusion protein (SEQ ID NO: 107) mc-vc-PAB-MMAE conjugates (DAR 2) in SNU16 cells are shown.

[0062] Figure 10 CDH17 expression in primary tumor biopsy core samples assessed by immunohistochemistry (IHC) is shown.

[0063] Figures 11A-11B Representative in vitro cancer cell drug sensitivity plots of BHB156-vedotin (DAR4) against representative CDH17+ cancer cell lines Figure 11A ) and primary patient-derived xenograft (PDX) cancer cell tissues Figure 11B ) are shown.

[0064] Figure 12 Summary table of cell line sensitivity calculated from IC 50 estimates derived from in vitro serial dilution of BHB156-vedotin (DAR4) or isotype control vedotin ADC, and receptor density measured by antibody binding capacity (ABC) of CDH17 molecules per cell surface.

[0065] Figure 13 Summary table of cell line sensitivity calculated from IC 50 estimates derived from in vitro serial dilution of BHB156-vedotin (DAR4) or isotype control vedotin ADC, and receptor density and IHC score measured by antibody binding capacity (ABC) of CDH17 molecules per cell surface.

[0066] Figure 14 Representative plots and summary table of plasma clearance of single dose of I-125 radiolabeled BHB156 or anti-SARS-CoV-2 isotype control VHH-Fc fusion protein at different concentrations in Sprague-Dawley rats are shown.

[0067] Figure 15 Representative biodistribution of I-125 radiolabeled BHB156 or anti-SARS-CoV-2 isotype control VHH-Fc fusion protein at 20 mg / kg single dose in Sprague-Dawley rats evaluated at 3 or 10 days post administration are shown.

[0068] Figures 16A-16D Efficacy of BHB156-vedotin (DAR4) versus isotype vedotin in clearing tumor burden in mice bearing cell line-derived xenograft (CDX) tumors is shown. DETAILED DESCRIPTION

[0069] SUMMARY

[0070] In some aspects, 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 substantially increased binding affinity and increased inhibition of CDH17 activity. In some aspects, the anti-CDH17 antibodies can comprise at least one genetic modification that results in a substitution, deletion, or insertion of at least one amino acid of a polypeptide encoding an anti-CDH17 or antigen-binding fragment thereof.

[0071] In some aspects, the anti-CDH17 antibodies or antigen-binding fragments thereof provided herein can be Fab, Fab', Fab'-SH, F(ab')2, Fv, TaFv, scFv, diabody, bsDb, scDb, DART, BiTE, and VHH fragments. For example, the anti-CDH17 antibodies or antigen-binding fragments thereof described herein can be a multispecific antigen-binding protein (e.g., bispecific T-cell engaging antibody) that binds to an antigen of interest (e.g., a protein) with sufficient affinity such that the multispecific antigen-binding protein can be used as a diagnostic and / or therapeutic agent to target the protein or a cell, tissue, or tumor expressing the protein, and does not significantly cross-react with other proteins. The present disclosure can be a bispecific antibody (BsAb) capable of binding CD3 and CDH17.

[0072] In some aspects, the anti-CDH17 antibodies provided herein can comprise anti-CDH17 antibodies or fragments and portions thereof (e.g., cytotoxic agents, Fc domains). For example, the anti-CDH17 antibody or fragment composition can be an anti-CDH17 antibody or antigen-binding fragment thereof conjugated to a cytotoxic agent and / or 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.

[0073] Anti-CDH17 immunotherapy has important prospects in the treatment of a variety of hematological and solid tissue malignancies. It is recognized herein that there is an unmet need to design engineered anti-CDH17 antibody compositions with enhanced binding affinity to CDH17. Disclosed herein are methods of designing engineered anti-CDH17 antibody compositions with enhanced binding affinity to CDH17.

[0074] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) a HCDR2 having the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a 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 antibodies or antigen-binding fragments thereof comprise at least one of: (a) a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, (b) a HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or ab antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies.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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, an emtansine, a pasudotox, a maytansinoid derivative DM1, a maytansinoid derivative DM4, a pyrrolobenzodiazepine. a PBD dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amanitin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, Amberstatin 269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleuine-dolaproine-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleuine-dolaproine-norephedrine, deruxtecan, tesirine, mertansine, ravtansine, a duocarmycin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, use of an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition in the manufacture of a medicament for the treatment of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0075] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) a 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) a HCDR3 having the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise at least one of: (a) a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, (b) a HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or ab antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies.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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, a maytansinoid derivative DM1, a maytansinoid derivative DM4, a pyrrolobenzodiazepine. a PBD dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-proline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-proline-nor-ephedrine, deruxitencan, texilicin, maytansine, a ratanine, a duocarmycin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0076] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 43, and / or a HCDR3 set forth in SEQ ID NO: 62. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or ab antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, multispecific binding molecules comprising a first binding domain and a second binding domain are disclosed herein, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain are disclosed herein. In some embodiments, the cytotoxic agent comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomon toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine (PBD) dimer, benzodiazepine , CC-1065 analogs, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , AZ13599 185, calicheamicin, rhizoxin, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, alpha-amanitin, a-amanitin, spliceostatin, tubulysins, ozogamicin, ambellastatin 269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, tesirine, maytansinoid, latanoprost, duocarmycin, calicheamicin, N-acetyl-gamma-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0077] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 44, and / or a HCDR3 set forth in SEQ ID NO: 63. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 3. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or ab antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, multispecific binding molecules comprising a first binding domain and a second binding domain are disclosed herein, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain are disclosed herein. In some embodiments, the cytotoxic agent comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomon toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine (PBD) dimer, benzodiazepine , CC-1065 analogs, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , AZ13599 185, calicheamicin, rhizoxin, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, alpha-amanitin, a-amanitin, spliceostatin, tubulysins, ozogamicin, ambellastatin 269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, tesirine, maytansinoid, latanoprost, duocarmycin, calicheamicin, N-acetyl-gamma-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0078] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 43, and / or a HCDR3 set forth in SEQ ID NO: 64. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 4. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, multispecific binding molecules comprising a first binding domain and a second binding domain are disclosed herein, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain are disclosed herein. In some embodiments, the cytotoxic agent comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomon toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine (PBD) dimer, benzodiazepine , CC-1065 analogs, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , AZ13599 185, calicheamicin, rhizoxin, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, alpha-amanitin, a-amanitin, spliceostatin, tubulysins, ozogamicin, ambellastatin 269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, tesirine, maytansinoid, latanoprost, duocarmycin, calicheamicin, N-acetyl-gamma-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0079] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 45, and / or a HCDR3 set forth in SEQ ID NO: 65. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 5. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, multispecific binding molecules comprising a first binding domain and a second binding domain are disclosed herein, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain are disclosed herein. In some embodiments, the cytotoxic agent comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomon toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine (PBD) dimer, benzodiazepine , CC-1065 analogs, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , AZ13599 185, cyanophos, rhizoxin, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, alpha-amanitin, a-amanitin, spliceostatin, tubulysins, ozogamicin, ambellstat 269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinodif), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, tesirine, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0080] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 46, and / or a HCDR3 set forth in SEQ ID NO: 65. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, multispecific binding molecules comprising a first binding domain and a second binding domain are disclosed herein, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain are disclosed herein. In some embodiments, the cytotoxic agent comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomon toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine (PBD) dimer, benzodiazepine , CC-1065 analogs, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , AZ13599 185, cyanophos, rhizoxin, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, alpha-amanitin, a-amanitin, spliceostatin, tubulysins, ozogamicin, ambellstat 269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinodif), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, tesirine, maytansinoid, latanoprost, duocarmycin, calicheamicin, N-acetyl-gamma-calicheamicin, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0081] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 47, and / or a HCDR3 set forth in SEQ ID NO: 72. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise an amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 109. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, multispecific binding molecules comprising a first binding domain and a second binding domain are disclosed herein, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain are disclosed herein. In some embodiments, the cytotoxic agent comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomon toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine (PBD) dimer, benzodiazepine , CC-1065 analogs, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , AZ13599 185, cyanophos, rhizoxin, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, alpha-amanitin, a-amanitin, spliceostatin, tubulysins, ozogamicin, ambellstat 269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinodif), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, tesirine, maytansinoid, latanoprost, duocarmycin, calicheamicin, N-acetyl-gamma-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0082] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 46, and / or a HCDR3 set forth in SEQ ID NO: 65. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, multispecific binding molecules comprising a first binding domain and a second binding domain are disclosed herein, wherein the first binding domain comprises an anti-CDH17 antibody or antigen-binding fragment thereof. In some embodiments, proteins comprising an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein conjugated to a cytotoxic agent and / or an Fc domain are disclosed herein. In some embodiments, the cytotoxic agent comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomon toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine (PBD) dimer, benzodiazepine , CC-1065 analogs, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , AZ13599 185, cyanophos, rhizoxin, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, alpha-amanitin, a-amanitin, spliceostatin, tubulysins, ozogamicin, ambellstat 269, soravtansine, dolastatin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinodif), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, tesirine, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0083] Provided herein is an anti-CDH17 antibody or antigen-binding fragment 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 two, three, four, five, six, or seven 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 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, a Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine. (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, texilicin, maytansine, a latrunculin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0084] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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 antibodies or antigen-binding fragments thereof comprise a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, 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. In some embodiments, provided 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine. (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, texilicin, maytansine, a latrunculin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0085] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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 antibodies or antigen-binding fragments thereof comprise a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, 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. In some embodiments, provided 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine. (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, texilicin, maytansine, a latrunculin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0086] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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 antibodies or antigen-binding fragments thereof comprise a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, 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. In some embodiments, provided 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine. (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, texilicin, maytansine, a latrunculin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0087] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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 D or F, and X5 is M or H; and (c) a 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 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, a Fv fragment, a single domain antibody, a diabody, a fragment consisting of only a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine. (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, texilicin, maytansine, a latrunculin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedghog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENP P3, a tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0088] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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 antibodies or antigen-binding fragments thereof comprise a T67V mutation in the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof comprise 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 antibodies or antigen-binding fragments thereof are monoclonal antibodies, polyclonal antibodies, bispecific antibodies, multispecific antibodies, grafted antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies, single-chain Fvs (scFv), single-chain antibodies, Fab fragments, F(ab')2 fragments, Fd fragments, Fv fragments, single-domain antibodies, diabodies, fragments consisting of only a single monomeric variable domain, disulfide-linked Fvs (sdFv), intrabodies, anti-idiotypic (anti-Id) antibodies, VHH antibodies, or antigen-binding fragments thereof. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are scFv antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are VHH antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are humanized. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are non-human antibodies. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof are human antibodies. In some embodiments, 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. In some embodiments, provided 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine. (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, texilicin, maytansine, a latrunculin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0089] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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 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, a Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine. (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MM AE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-norephedrine, deruxitencan, texilicin, maytansine, a latrunculin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0090] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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 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, a Fv fragment, a single domain antibody, a diabody, a fragment consisting of only a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine. (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, texilicin, maytansine, a latrunculin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedghog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENP P3, a tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0091] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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 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, a Fv fragment, a single-domain antibody, a diabody, a fragment consisting of only a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine. (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MM AE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-norephedrine, deruxitencan, texilicin, maytansine, a latrunculin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0092] Provided herein is an anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a HCDR3 having the amino acid sequence TX6GX7AX8SVRL (SEQ ID NO: 87), wherein 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, a Fv fragment, a single domain antibody, a diabody, a fragment consisting of only a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine. (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a-amanitin, a spliceostatin, a thailanstatin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisoleucine-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisoleucine-dolaproline-nor-ephedrine, deruxitencan, texilicin, maytansine, a latrunculin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0093] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 11 GX 12 X13X 14 EYX 15 X 16 X 17 VX18 G (SEQ ID NO:88), wherein X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence of TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO:89), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0094] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WRGX 12 X13X 14 EYX 15 X 16 X 17 VX18 G (SEQ ID NO: 90) wherein X 10 is S or D, X 12 is E, N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) a HCDR3 of the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) wherein X 19 is H or Y, X 20 is G, T, V, K or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-gamma-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0095] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X17 VX 18 G (SEQ ID NO: 91) HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) has an amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) HC DR3, wherein X 19 is H or Y, X 20 is G, T, V, K or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine (PBD) dimer, benzodiazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-gamma-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0096] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX 12 YX 14 EYX 15 X 16 X 17VX 18 G (SEQ ID NO: 92) HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) HCDR3, wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-gamma-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0097] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX12X 13 SEYX 15 X 16 X 17 VX18 G (SEQ ID NO: 93) HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) HCDR3, wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0098] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X17 VX 18 G (SEQ ID NO: 94) wherein X 10 is S or D, X 11 is N or R, X 12 is N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) has an amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) wherein X 19 is H or Y, X 20 is G, T, V, K or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0099] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX12X 13 X 14 EYX 15 EX 17 VX18 G (SEQ ID NO: 95) HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) HCDR3, wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0100] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X17 VX 18 G (SEQ ID NO: 94) wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is D, F or T, and X 18 is M or H; and (c) has an amino acid sequence of TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 96) wherein X 19 is H or Y, X 20 is G, T, V, K or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , azathioprine, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0101] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X17 HCDR2 of VHG (SEQ ID NO:97), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T; and (c) has the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 HCDR3 of VHG (SEQ ID NO:97), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0102] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X17 VX 18 G (SEQ ID NO: 94) HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has the amino acid sequence TYGX 20 AX 21 SVRX 22 (SEQ ID NO: 98) HCDR3, wherein X 20 is G, T, V, K, or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0103] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X17 VX 18 G (SEQ ID NO: 94) HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) HCDR3, wherein X 19 is H or Y, X 20 is T, V, K, or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0104] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X17 VX 18 G (SEQ ID NO: 94) HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has an amino acid sequence of TX 19 GX 20 AKSVRX 22 (SEQ ID NO: 99) HC DR3, wherein X 19 is H or Y, X 20 is G, T, V, K, or N, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0105] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence 10 WX 11 GX12X 13 X 14 EYX 15 X 16 X17 VX 18 G (SEQ ID NO: 94) HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is D, F, or T, and X 18 is M or H; and (c) has the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) HC DR3, wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22S, 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 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanacin, pseudomonotubacin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzo-diazepine (PBD) dimer, benzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0106] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof, wherein the anti-CDH17 antibodies or antigen-binding fragments thereof have increased binding affinity for CDH17 compared to the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1 for CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibodies or antigen-binding fragments thereof for CDH17 is at least 3-fold greater than the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1 for CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibodies or antigen-binding fragments thereof for CDH17 is at least 5-fold greater than the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1 for CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibodies or antigen-binding fragments thereof for CDH17 is at least 10-fold greater than the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1 for CDH17. In some embodiments, the binding affinity of the anti-CDH17 antibodies or antigen-binding fragments thereof for CDH17 is at least 15-fold greater than the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1 for CDH17. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof bind to CDH17 with a KD of less than 1.0 X 10 -8 M. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof bind to CDH17 with a KD of less than 5.0 X 10 -9 M. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof bind to CDH17 with a KD of less than 3.0 X 10 -9 M. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof bind to CDH17 with a KD of less than 1.0 X 10 -9 M. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof inhibit CDH17 activity with an IC 50 of less than 100.0 X 10 -12 M. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof inhibit CDH17 activity with an IC 50 of less than 50.0 X 10 50 M. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have an IC -12 for CDH17 that is at least 1 / 10 of the IC 50 for CDH17 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 an IC 50 for CDH17 that is at least 1 / 5 of the IC 50 for CDH17 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 an IC 50at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) a HCDR2 having the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a 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) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) a 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) a 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) a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, (b) a HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 43, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 44, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 43, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 45, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 46, and / or a 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 two, three, four, five, six, or seven 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWRGX2NAEYX3DX4VX5G (SEQ ID NO: 79), wherein X2is E or N, X3is S or R, X4is S, D, or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K, or N, X8is R or K, and X9is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO:41); (b) a HCDR2 having the amino acid sequence LLSWX1GNNAEYX3DX4VX5G (SEQ ID NO:81), wherein X1is N or R, X3is S or R, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO:80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO:41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYRDX4VX5G (SEQ ID NO:82), wherein X1is N or R, X2is E or N, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO:80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO:41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO:83), wherein X1is N or R, X2is E or N, X3is S or R, X4is D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO:80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO:41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VHG (SEQ ID NO:84), wherein X1is N or R, X2is E or N, X3is S or R, and X4is S, D or F; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO:80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TYGX7AX8SVRX9(SEQ ID NO: 85), wherein X7is G, T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AKSVRX9(SEQ ID NO: 86), wherein X6is H or Y, X7is G, T, V, K or N, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRL (SEQ ID NO: 87), wherein X6is H or Y, X7is G, T, V, K or N, and X8is 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLDWX. 11 GX 12 X 13 X 14 EY X 15 X 16 X 17 VX 18 G(SEQ ID NO:88) of the HCDR2, wherein X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, 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) a HCDR 1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLDWX 10 WRGX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 G(SEQ ID NO: 90) of the HCDR2, wherein X 10 is S or D, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21SVRX 22 HCDR3 of (SEQ ID NO:89), where X 19 Is it H or Y, X 20 Is it G, T, V, K, or N, X 21 It is R or K, and X 22 It is S, L, K, or A. In some embodiments, the anti-CDH17 antibody or its antigen-binding fragment comprises: (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 HCDR 2 of G (SEQ ID NO:91), where X 10 Is it S or D, X 11 Is it N or R, X 12 Is it N, I, or Y, X 13 Is it N or Y, X 14 Is it A or S, X 15 Is it S, R, or A, X 16 Is it D or E, X 17 It is S, D, F, or T, and X 18 It is M or H; and (c) has the amino acid sequence TX. 19 GX 20 AX 21 SVRX 22 HCDR3 of (SEQ ID NO:89), where X 19 Is it H or Y, X 20 Is it G, T, V, K, or N, X 21 It is R or K, and X 22 It is S, L, K, or A. In some embodiments, the anti-CDH17 antibody or its antigen-binding fragment comprises: (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO:41); (b) having the amino acid sequence LLX 10 WX 11 GX 12 YX 14 EYX 15 X 16 X 17 VX 18 G(SEQ ID NO:92) of HCDR2, where X 10 Is it S or D, X 11 Is it N or R, X 12 Is it E, N, I, or Y, X14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) has an amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) wherein X 19 is H or Y, X 20 is G, T, V, K or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 SEYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 93) wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I or Y, X 13 is N or Y, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) has an amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) wherein X 19 is H or Y, X 20 is G, T, V, K or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX​​​​​​​​​​​​​​​​​​​​​​​​15 X16X 17 VX 18 G(SEQ ID NO:94) HCDR2, where X 10 Is it S or D, X 11 Is it N or R, X 12 Is it E, N, I, or Y, X 13 Is it N or Y, X 14 Is it A or S, X 15 Is it R or A, X 16 Is it D or E, X 17 It is S, D, F, or T, and X 18 It is M or H; and (c) has the amino acid sequence TX. 19 GX 20 AX 21 SVRX 22 HCDR3 of (SEQ ID NO:89), where X 19 Is it H or Y, X 20 Is it G, T, V, K, or N, X 21 It is R or K, and X 22 It is S, L, K, or A. In some embodiments, the anti-CDH17 antibody or its antigen-binding fragment comprises: (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO:41); (b) having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 EX 17 VX 18 G(SEQ ID NO:95) of HCDR2, where X 10 Is it S or D, X 11 Is it N or R, X 12 Is it E, N, I, or Y, X 13 Is it N or Y, X 14 Is it A or S, X 15 Is it S, R, or A, X 17 It is S, D, F, or T, and X 18 It is M or H; and (c) has the amino acid sequence TX. 19 GX 20 AX 21 SVRX 22 HCDR3 of (SEQ ID NO: 89), where X 19 Is it H or Y, X 20 Is it G, T, V, K, or N, X 21 It is R or K, and X 22is S, L, K, or A. In some embodiments, the anti-CDH 17 antibody or antigen-binding fragment thereof comprises: (a) an HC DR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HC DR2 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), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is D, F, or T, and X 18 is M or H; and (c) an HC DR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 96), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A. In some embodiments, the anti-CDH 17 antibody or antigen-binding fragment thereof comprises: (a) an HC DR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HC DR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VHG (SEQ ID NO: 97), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T; and (c) an HC DR3 having the amino acid sequence TX19 GX 20 AX 21 SVRX 22 (SEQ ID NO:89) of HCDR3, wherein X 19 is H or Y, X 20 is G, T, V, K, or N, 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 GX12X 13 X 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO:94) of HCDR 2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) an HCDR3 having the amino acid sequence TYGX 20 AX 21 SVRX 22 (SEQ ID NO:98) of HCDR3, wherein X 20 is G, T, V, K, or N, 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 G (SEQ ID NO:94) of HCDR 2, wherein X 10 is S or D, X 11 is N or R, X 12is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has an amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) wherein X 19 is H or Y, X 20 is T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A. In some embodiments, the anti-CDH 17 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) wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has an amino acid sequence TX 19 GX 20 AKSVRX 22 (SEQ ID NO: 99) wherein X 19 is H or Y, X 20 is G, T, V, K, or N, and X 22 is S, L, K, or A. In some embodiments, the anti-CDH 17 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 X13 X 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 94) wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) has an amino acid sequence of TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) wherein X 19 is H or Y, X 20 is G, T, V, K or N, X 21 is R or K, and X 22L, 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanine, a pseudomonas toxin, a maytansinoid derivative DM1, a maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-γ-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedghog inhibitor, a nitrogen mustard, and a histone deacetylase inhibitor, PE38, SN-38, ENP P3, a tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of a cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0107] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof, wherein the anti-CDH17 antibodies or antigen-binding fragments thereof have 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 antibodies or antigen-binding fragments thereof to CDH17 is measured by melting temperature (Tm). In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have a Tm of less than 70 °C. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have a Tm of less than 60 °C. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have a Tm of less than 50 °C. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) a HCDR2 having the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a 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 antibodies or antigen-binding fragments thereof comprise: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) a 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) a HCDR3 having the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise at least one of: (a) a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, (b) a HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 43, and / or a HCDR3 set forth in SEQ ID NO: 62. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 44, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 43, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 45, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 46, and / or a 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 of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the at least one amino acid substitution comprises at least two, three, four, five, six, or seven 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWRGX2NAEYX3DX4VX5G (SEQ ID NO: 79), wherein X2is E or N, X3is S or R, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GNNAEYX3DX4VX5G (SEQ ID NO: 81), wherein X1is N or R, X3is S or R, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYRDX4VX5G (SEQ ID NO: 82), wherein X1is N or R, X2is E or N, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VHG (SEQ ID NO: 84), wherein X1is N or R, X2is E or N, X3is S or R, and X4is S, D, or F; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K, or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D, or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TYGX7AX8SVRX9(SEQ ID NO: 85), wherein X7is G, T, V, K, or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D, or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is T, V, K, or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D, or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AKSVRX9(SEQ ID NO: 86), wherein X6is H or Y, X7is G, T, V, K, or N, and X9is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) an HC DR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) an HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D or F, and X5is M or H; and (c) an HCDR3 having the amino acid sequence TX6GX7AX8SVRL (SEQ ID NO: 87), wherein X6is H or Y, X7is G, T, V, K or N, and X8is 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 G(SEQ ID NO: 88), wherein X 11 is N or R, X 12 is E, N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) an HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K or N, 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 LLSX 10 WRGX 12 X 13 X 14 EYX 15X 16 X 17 VX 18 G (SEQ ID NO: 90) in which X 10 is S or D, X 12 is E, N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) has the HCDR3 of TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) in which X 19 is H or Y, X 20 is G, T, V, K or N, 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) the HCDR1 of YDMG (SEQ ID NO: 41); (b) the HCDR2 of LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 91) in which X 10 is S or D, X 11 is N or R, X 12 is N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) has the HCDR3 of TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) in which X 19 is H or Y, X 20 is G, T, V, K or N, X 21 is R or K, and X 22S, L, K, or A. In some embodiments, the anti-CDH 17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 YX 14 EYX 15 X 16 X 17 VX 18 G(SEQ ID NO: 92), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A. In some embodiments, the anti-CDH 17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 SEYX 15 X 16 X 17 VX 18 G(SEQ ID NO: 93), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A. In some embodiments, the anti-CDH 17 antibody, or antigen binding fragment thereof, comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X16X 17 VX 18 G (SEQ ID NO: 94), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is R or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A. In some embodiments, the anti-CDH 17 antibody, or antigen binding fragment thereof, comprises: (a) a HCDR 1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 EX 17 VX 18 G (SEQ ID NO: 95), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 17 is S, D, F or T, and X 18 is M or H; and (c) has an amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) wherein X 19 is H or Y, X 20 is G, T, V, K or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is D, F or T, and X 18 is M or H; and (c) has an amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 96) wherein X 19 is H or Y, X 20 is G, T, V, K or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X13 X 14 EYX 15 X 16 X 17 VHG (SEQ ID NO: 97) of HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T; and (c) HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) of HCDR3, wherein X 19 is H or Y, X 20 is G, T, V, K, or N, 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) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) 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) of HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) HCDR3 having the amino acid sequence TYGX 20 AX 21 SVRX 22 (SEQ ID NO: 98) of HCDR3, wherein X 20 is G, T, V, K, or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is T, V, K, or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EY X 15 X 16 X 17 VX 18 G(SEQ ID NO: 94), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X18 is M or H; and (c) has an amino acid sequence TX 19 GX 20 AKSVRX 22 (SEQ ID NO: 99) wherein X 19 is H or Y, X 20 is G, T, V, K, or N, and X 22 is S, L, K, or A. In some embodiments, the anti-CDH 17 antibody, or antigen binding fragment thereof, comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has an amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89) wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22L, 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (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 a 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 is a multispecific binding molecule 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 is a protein 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 comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin-targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emitanine, a pseudomonas toxin, a maytansinoid derivative DM1, a maytansinoid derivative DM4, a pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine (PBD) dimer, a benzodiazepine , a CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine , aziridines, methotrexate, anthracyclines, camptothecin analogs, DX-8951f, exatecan mesylate, duocarmycin derivatives, α-amanitin, a-amanitin, splicing inhibitors, thailanstatin, ozogamicin, ambellstatin 269, soravtansine, doramapimycin 10, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl doramapimycin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, tesirine, maytansine, ratanine, duocarmycin, calicheamicin, N-acetyl-gamma-calicheamicin, maytansinoid, pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a-amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB). In some embodiments, disclosed herein are nucleic acids encoding an anti-CDH17 antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a multispecific binding molecule disclosed herein. In some embodiments, disclosed herein are nucleic acids encoding a protein 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, an 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 used in therapy. In some embodiments, an 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 used in therapy, wherein the therapy is antibody monotherapy, antibody-drug conjugate (ADC) therapy, T cell engaging immunotherapy, or CAR-T therapy. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the manufacture of a medicament for treating cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer. In some embodiments, an anti-CDH17 antibody or antigen-binding fragment thereof, a multispecific binding molecule, a protein, a conjugate, a nucleic acid, an expression vector, a host cell, or a pharmaceutical composition is used in the diagnosis of cancer. In some embodiments, the cancer is gastric cancer, pancreatic cancer, a neuroendocrine cancer, or colorectal cancer.

[0108] Provided herein are anti-CDH17 antibodies or antigen-binding fragments thereof, wherein the anti-CDH17 antibodies or antigen-binding fragments thereof have 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, the purity is measured by capillary gel electrophoresis using sodium dodecyl sulfate (CE-SDS). In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) a HCDR2 having the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a 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 antibodies or antigen-binding fragments thereof comprise: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 41, (b) a 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) a HCDR3 having the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise at least one of: (a) a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, (b) a HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-75. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof have at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the anti-CDH17 antibodies or antigen-binding fragments thereof comprise a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 43, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 44, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 43, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 45, and / or a 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 a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 46, and / or a 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 of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the at least one amino acid substitution comprises at least two, three, four, five, six, or seven 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) a HCDR1 having the amino acid sequence YD MG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSW RGX2NAEYX3DX4VX5G (SEQ ID NO: 79), wherein X2is E or N, X3is S or R, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GNNAEYX3DX4VX5G (SEQ ID NO: 81), wherein X1is N or R, X3is S or R, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYRDX4VX5G (SEQ ID NO: 82), wherein X1is N or R, X2is E or N, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K or N, X8is R or K, and X9is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VHG (SEQ ID NO: 84), wherein X1is N or R, X2is E or N, X3is S or R, and X4is S, D, or F; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is G, T, V, K, or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D, or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TYGX7AX8SVRX9(SEQ ID NO: 85), wherein X7is G, T, V, K, or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D, or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRX9(SEQ ID NO: 80), wherein X6is H or Y, X7is T, V, K, or N, X8is R or K, and X9is S or L. In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D, or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AKSVRX9(SEQ ID NO: 86), wherein X6is H or Y, X7is G, T, V, K, or N, and X9is S or L.In some embodiments, the anti-CDH17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX1GX2NAEYX3DX4VX5G (SEQ ID NO: 83), wherein X1is N or R, X2is E or N, X3is S or R, X4is S, D or F, and X5is M or H; and (c) a HCDR3 having the amino acid sequence TX6GX7AX8SVRL (SEQ ID NO: 87), wherein X6is H or Y, X7is G, T, V, K or N, and X8is 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLDWX. 11 GX 12 X 13 X 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 88), wherein X 11 is N or R, X 12 is E, N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is S, D, F or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLSWX. 10 WRGX 12 X 13 X 14 EYX 15 X16 X 17 VX 18 G(SEQ ID NO:90) of HCDR2, where X 10 Is it S or D, X 12 Is it E, N, I, or Y, X 13 Is it N or Y, X 14 Is it A or S, X 15 Is it S, R, or A, X 16 Is it D or E, X 17 It is S, D, F, or T, and X 18 It is M or H; and (c) has the amino acid sequence TX. 19 GX 20 AX 21 SVRX 22 HCDR3 of (SEQ ID NO:89), where X 19 Is it H or Y, X 20 Is it G, T, V, K, or N, X 21 It is R or K, and X 22 It is S, L, K, or A. In some embodiments, the anti-CDH17 antibody or its antigen-binding fragment comprises: (a) HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) 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:91) HCDR2, where X 10 Is it S or D, X 11 Is it N or R, X 12 Is it N, I, or Y, X 13 Is it N or Y, X 14 Is it A or S, X 15 Is it S, R, or A, X 16 Is it D or E, X 17 It is S, D, F, or T, and X 18 It is M or H; and (c) has the amino acid sequence TX. 19 GX 20 AX 21 SVRX 22 HCDR3 of (SEQ ID NO:89), where X 19 Is it H or Y, X 20 Is it G, T, V, K, or N, X 21 It is R or K, and X 22S, L, K, or A. In some embodiments, the anti-CDH 17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 YX 14 EYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 92), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, X 21 is R or K, and X 22 is S, L, K, or A. In some embodiments, the anti-CDH 17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 SEYX 15 X 16 X 17 VX 18 G (SEQ ID NO: 93), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX21 SVRX 22 (SEQ ID NO:89) wherein X 19 is H or Y, X 20 is G, T, V, K, or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO:41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 X16X 17 VX 18 G (SEQ ID NO:94) wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is R or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO:89) wherein X 19 is H or Y, X 20 is G, T, V, K, or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO:41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X 13 X 14 EYX 15 EX 17 VX 18 G (SEQ ID NO:95) wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 17 is S, D, F or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R or A, X 16 is D or E, X 17 is D, F or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 96), wherein X 19 is H or Y, X 20 is G, T, V, K or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a HCDR2 having the amino acid sequence LLX 10 WX 11 GX 12 X13 X 14 EYX 15 X 16 X 17 VHG (SEQ ID NO: 97) HCDR2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T; and (c) has the HCDR3 of amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is G, T, V, K, or N, 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) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) HCDR 2, wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) has the HCDR3 of amino acid sequence TYGX 20 AX 21 SVRX 22 (SEQ ID NO: 98), wherein X 20 is G, T, V, K, or N, X 21 is R or K, and X 22is S, L, K, or A. In some embodiments, the anti-CDH 17 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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), wherein X 10 is S or D, X 11 is N or R, X 12 is E, N, I, or Y, X 13 is N or Y, X 14 is A or S, X 15 is S, R, or A, X 16 is D or E, X 17 is S, D, F, or T, and X 18 is M or H; and (c) a HCDR3 having the amino acid sequence TX 19 GX 20 AX 21 SVRX 22 (SEQ ID NO: 89), wherein X 19 is H or Y, X 20 is T, V, K,...

Claims

1. An anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41, (b) a HCDR2 having the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a 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) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41, (b) a 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) a 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 of claim 1 or 2, wherein the anti-CDH17 antibody or antigen-binding fragment thereof comprises at least one of: (a) a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, (b) a HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 43-60, and (c) a HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 62-75.

4. An anti-CDH17 antibody or antigen-binding fragment thereof, comprising: (a) a HCDR1 having the amino acid sequence YDMG (SEQ ID NO: 41); (b) a 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) a 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.

5. The anti-CDH17 antibody or antigen-binding fragment thereof of claim 4, wherein X2 is N, X3 is S, X4 is S, and X5 is M, X6 is Y, X7 is G, X8 is R, and X9 is S.

6. The anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1-5, 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: 2-40 or 109.

7. An anti-CDH17 antibody or antigen-binding fragment thereof, comprising a HCDR1 set forth in SEQ ID NO: 41, a HCDR2 set forth in SEQ ID NO: 47, and / or a HCDR3 set forth 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 an amino acid sequence set forth in SEQ ID NO:

109.

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

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 for CDH17 is at least 3-fold, at least 5-fold, at least 10-fold, or at least 15-fold greater than the binding affinity of the amino acid sequence set forth in SEQ ID NO: 1 for CDH17.

11. The anti-CDH 17 antibody or antigen-binding fragment thereof of any one of claims 1-10, wherein the anti-CDH 17 antibody or antigen-binding fragment thereof binds to CDH 17 with a KD of less than 1.0 X 10 -8 M, 5.0 X 10 -9 M, or 3.0 X 10 -9 M.

12. The anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1-11, 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, wherein the stability of the anti-CDH17 antibody or antigen-binding fragment thereof for CDH17 is measured by melting temperature (Tm).

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 of any one of claims 1-13, 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.

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-CDHl 7 antibody or antigen-binding fragment thereof of any one of claims 1-15, wherein the anti-CDHl 7 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 a single monomeric variable domain, a disulfide-linked Fv (sdFv), an intrabody, an anti-idiotypic (anti-Id) antibody, a VHH antibody, or an ab antigen-binding fragment thereof.

17. The anti-CDHl 7 antibody or antigen-binding fragment thereof of any one of claims 1-16, wherein the anti-CDHl 7 antibody or antigen-binding fragment thereof is a VHH antibody.

18. The anti-CDHl 7 antibody or antigen-binding fragment thereof of any one of claims 1-17, wherein the anti-CDHl 7 antibody or antigen-binding fragment thereof is humanized.

19. The anti-CDHl 7 antibody or antigen-binding fragment thereof of any one of claims 1-18, wherein the anti-CDHl 7 antibody or antigen-binding fragment thereof is a human antibody.

20. A conjugate comprising Formula (I): Ab-(L-D)n Formula (I) wherein Ab comprises an anti-CDHl 7 antibody or antigen-binding fragment thereof, wherein the anti-CDHl 7 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:41, (b) a 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) a 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 to antibody ratio, wherein the drug to antibody ratio is about 1 to about 8.

21. The conjugate of claim 20, wherein the anti-CDHl 7 antibody or antigen-binding fragment thereof comprises: (a) a HCDR1 having the amino acid sequence set forth in SEQ ID NO:41, (b) a HCDR2 having the amino acid sequence set forth in SEQ ID NO:47, and (c) a HCDR3 having the amino acid sequence set forth in SEQ ID NO:

72.

22. The conjugate of claim 20 or 21, wherein the anti-CDHl 7 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 20-22, wherein the anti-CDHl 7 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 20-23, wherein the anti-CDH17 antibody or antigen-binding fragment thereof further comprises an Fc domain.

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

26. The conjugate of any one of claims 20-25, wherein the cytotoxic agent comprises a ribosome-targeting toxin, an elongation factor-targeting toxin, a tubulin- targeting toxin, a DNA-targeting toxin, an RNA-targeting toxin, emtansine, a pseudomonas toxin, maytansinoid derivative DM1, maytansinoid derivative DM4, pyrrolobenzodiazepine (PBD) dimer, a benzodiazepine CC-1065 analog, paclitaxel, docetaxel, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil (5-FU), mitoxantrone, an indolinobenzodiazepine AZ13599185, a cyanobipyrrole, rhizoxin, methotrexate, an anthracycline, a camptothecin analog, DX-8951f, exatecan mesylate, a duocarmycin derivative, an amatoxin, a- amanitin, a spliceostatin, a tubulysin, an ozogamicin, an ambritin 269, a soravtansine, a dolastatin 10, an auristatin E, an auristatin EB (AEB), an auristatin EFP (AEFP), monomethyl auristatin D (MMAD), monomethyl dolastatin 10, monomethyl auristatin F (MMAF, maytansinol), N-methylvaline-valine-dolaisole-dolaproline-phenylalanine, monomethyl auristatin E (MMAE, vedotin), N-methylvaline-valine-dolaisole-dolaproline-norephedrine, deruxitencan, texilicin, maytansine, ratanucine, a duocarmycin, a calicheamicin, N-acetyl-gamma-calicheamicin, a maytansinoid, a pyrrolobenzodiazepine (PBD), doxorubicin, an anthracycline, a camptothecin derivative, a taxane, a Hedgehog inhibitor, a nitrogen mustard and a histone deacetylase inhibitor, PE38, SN-38, ENPP3, tubulysin, exatecan, a STING agonist, a TLR agonist, a- amanitin, SGD-1882, CC-1065, or 5-benzoylvaleric acid-AE ester (AEVB).

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

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

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

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

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

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

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

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

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

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

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

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

39. A host cell comprising the nucleic acid of claim 36 or 37 or the expression vector of claim 38.

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

41. A pharmaceutical composition for treating cancer, comprising the anti-CDH17 antibody or antigen-binding fragment thereof of any one of claims 1-19, the conjugate of any one of claims 20-35, 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. The pharmaceutical composition of claim 41, wherein the pharmaceutical composition further comprises at least one additional therapeutic agent.

43. The anti-CDHl 7 antibody or antigen-binding fragment thereof of any one of claims 1- 19, the conjugate of any one of claims 20-35, 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. The anti-CDHl 7 antibody or antigen-binding fragment thereof of any one of claims 1- 19, the conjugate of any one of claims 20-35, 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. A method for treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the anti-CDHl 7 antibody or antigen-binding fragment thereof of any one of claims 1-19, the conjugate of any one of claims 20-35, 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-CDHl 7 antibody or antigen-binding fragment thereof of any one of claims 1-19, the conjugate of any one of claims 20-35, 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 treating cancer.

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

48. Use of the anti-CDHl 7 antibody or antigen-binding fragment thereof of any one of claims 1-19, the conjugate of any one of claims 20-35, 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, for diagnosing cancer.

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

50. A kit comprising the anti-CDHl 7 antibody or antigen-binding fragment thereof of any one of claims 1-19, the conjugate of any one of claims 20-35, 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, and instructions for use.

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