Anti-STEAP1 antigen-binding molecule and its use

Abstract

The present invention provides single-specificity and multi-specificity antigen-binding molecules and compositions thereof. The present invention also features methods of treating a disease or disorder such as cancer, methods of inhibiting tumor growth, and kits for use with one or more of such methods.

Description

Technical Field

[0001] Sequence Listing This application contains a sequence listing that was electronically submitted in XML format and is hereby incorporated by reference in its entirety. The XML copy created on July 18, 2023, is named "50474-301WO2_Sequence_Listing" and is 170,087 bytes in size.

[0002] Technical Field The present invention relates to antigen-binding molecules that bind to STEAP1, including monospecific and multispecific antibodies, compositions thereof, and methods of treating diseases such as cancer.

Background Art

[0003] Background Cancer is a heterogeneous disease that evolves at the genetic, phenotypic, and pathological levels. Current treatments include chemotherapy, radiation therapy, surgery, hormone therapy, targeted therapy, immunotherapy, and stem cell transplantation. Targeted therapy and immunotherapy have been shown to be promising in mediating the potent killing of tumor cells. However, intratumoral heterogeneity, the presence of cancer subtypes and mutations that lead to acquired resistance, pose challenges in target selection. There is still a need to develop therapeutic agents that recognize one or more targets shared among different cancer subtypes and therapeutic agents that have acquired resistance-driving mutations.

Summary of the Invention

[0004] Summary At least one aspect of the invention described herein relates to a multispecific antigen-binding molecule comprising: (A) a heavy-chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3 of a VH sequence selected from SEQ ID NOs: 7, 17-25, 30-34, 38, and 68; and a light-chain variable region (VL) that binds to STEAP1 and comprises CDR-L1, CDR-L2, and CDR-L3 of a VL sequence selected from SEQ ID NOs: 8, 26-29, 39, and 69, which together form a first antigen-binding domain; and (B) a second antigen-binding domain that binds to a T cell receptor.

[0005] At least another aspect of the invention described herein relates to a multispecific antigen-binding molecule comprising: (A) a heavy-chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3; and a light-chain variable region (VL) that binds to STEAP1 and comprises CDR-L1, CDR-L2, and CDR-L3, which together form a first antigen-binding domain; and (B) a second antigen-binding domain that binds to a T cell receptor. CDR-H1 is Xaa 1 Xaa 2 comprises YMA (SEQ ID NO: 35); wherein Xaa 1 is Asp (D) or Asn (N); and Xaa 2 is His (H), Tyr (Y), or Phe (F). CDR-H2 is YIXaa 3 YDGXaa 4 Xaa 5 TXaa 6 comprises YGDSVKG (SEQ ID NO: 36); wherein Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D), or Leu (L); Xaa 5 is Ser (S), Asp (D), or Asn (N); Xaa 6 is Ser (S) or Tyr (Y). CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9comprising (Sequence ID No. 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of Sequence ID No. 4; CDR-L2 comprises the amino acid sequence of Sequence ID No. 5; and CDR-L3 comprises the amino acid sequence of Sequence ID No. 6.

[0006] In some embodiments, CDR-H1 comprises the amino acid sequence of Sequence ID No. 10, 1, or 9.

[0007] In some embodiments, CDR-H2 comprises the amino acid sequence of Sequence ID No. 2, 11, 12, or 13.

[0008] In some embodiments, CDR-H3 comprises the amino acid sequence of Sequence ID No. 16, 3, 14, or 15.

[0009] In some embodiments, the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence of Sequence ID No. 10; CDR-H2 comprising the amino acid sequence of Sequence ID No. 2; CDR-H3 comprising the amino acid sequence of Sequence ID No. 16; CDR-L1 comprising the amino acid sequence of Sequence ID No. 4; CDR-L2 comprising the amino acid sequence of Sequence ID No. 5; and CDR-L3 comprising the amino acid sequence of Sequence ID No. 6.

[0010] In some embodiments, the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence of Sequence ID No. 1; CDR-H2 comprising the amino acid sequence of Sequence ID No. 2; CDR-H3 comprising the amino acid sequence of Sequence ID No. 3; CDR-L1 comprising the amino acid sequence of Sequence ID No. 4; CDR-L2 comprising the amino acid sequence of Sequence ID No. 5; and CDR-L3 comprising the amino acid sequence of Sequence ID No. 6.

[0011] In some embodiments, the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 11; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0012] In some embodiments, the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0013] In some embodiments, the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0014] In some embodiments, the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 13; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0015] In some embodiments, the multispecific antigen-binding molecule is a humanized antibody.

[0016] In some embodiments, the first antigen-binding domain and the second antigen-binding domain each independently comprise an IgG framework region, optionally an IgG1 or IgG4 framework region.

[0017] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68.

[0018] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69.

[0019] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 68, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 69.

[0020] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 34, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 27.

[0021] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 30, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 27.

[0022] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 31, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 27.

[0023] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 32, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 27.

[0024] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 33, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 27.

[0025] In some embodiments, the T cell receptor is cluster of differentiation 3 (CD3).

[0026] In some embodiments, the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the sequences of SEQ ID NOs: 48-53.

[0027] In some embodiments, the second antigen-binding domain that binds to CD3 comprises a VH sequence of an anti-CD3 heavy chain variable region having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 54, and a VL sequence of an anti-CD3 light chain variable region having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 55.

[0028] In some embodiments, the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the sequences of SEQ ID NOs: 40-45.

[0029] In some embodiments, the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 46, and an anti-CD3 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 47.

[0030] In some embodiments, the multispecific antigen-binding molecule comprises one or more heavy chain constant domains, and the one or more heavy chain constant domains are selected from a first CH1 (CH11) domain, a first CH2 (CH21) domain, a first CH3 (CH31) domain, a second CH1 (CH12) domain, a second CH2 (CH22) domain, and a second CH3 (CH32) domain.

[0031] In some embodiments, at least one of the one or more heavy chain constant domains is paired with another heavy chain constant domain.

[0032] In some embodiments, the CH31 domain and the CH32 domain each include a protrusion or a cavity, and the protrusion or cavity of the CH31 domain can be respectively disposed in the cavity or protrusion of the CH32 domain.

[0033] In some embodiments, the CH31 and CH32 domains associate at the interface between the protrusion and the cavity.

[0034] In some embodiments, the CH21 domain and the CH22 domain each include a protrusion or a cavity, and the protrusion or cavity of the CH21 domain can be respectively disposed in the cavity or protrusion of the CH22 domain.

[0035] In some embodiments, the CH21 and CH22 domains associate at the interface between the protrusion and the cavity.

[0036] In some embodiments, the first antigen-binding domain includes an anti-STEAP1 heavy chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 83 and an anti-STEAP1 light chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 82; the second antigen-binding domain includes an anti-CD heavy chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 85 and an anti-CD light chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 84.

[0037] In some embodiments, the antigen-binding molecule comprises an anti-STEAP1 heavy chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 85 and an anti-STEAP1 light chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 84; the second antigen-binding domain comprises an anti-CD3 heavy chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 83 and an anti-CD3 light chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 82.

[0038] In some embodiments, the multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 73, an anti-STEAP1 light chain comprising SEQ ID NO: 72, an anti-CD3 heavy chain comprising SEQ ID NO: 79, and an anti-CD3 light chain comprising SEQ ID NO: 78.

[0039] In some embodiments, the multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 73, an anti-STEAP1 light chain comprising SEQ ID NO: 72, an anti-CD3 heavy chain comprising SEQ ID NO: 81, and an anti-CD3 light chain comprising SEQ ID NO: 80.

[0040] In some embodiments, the multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 71, an anti-STEAP1 light chain comprising SEQ ID NO: 70, an anti-CD3 heavy chain comprising SEQ ID NO: 79, and an anti-CD3 light chain comprising SEQ ID NO: 78.

[0041] In some embodiments, the multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 71, an anti-STEAP1 light chain comprising SEQ ID NO: 70, an anti-CD3 heavy chain comprising SEQ ID NO: 81, and an anti-CD3 light chain comprising SEQ ID NO: 80.

[0042] In some embodiments, the antigen-binding molecule is a single-chain Fv (scFv), trispecific (Fab3), bispecific (Fab2), diabody ((VL-VH)2 or (VH-VL)2), triabody (trivalent), tetrabody (tetravalent), minibody ((scFv-CH)2), bispecific single-chain Fv (Bis-scFv), IgGdeltaCH2, scFv-Fc, or (scFv)2-Fc.

[0043] In some embodiments, the multispecific antigen-binding molecule is a multispecific antibody, preferably a bispecific or trispecific antibody.

[0044] In some embodiments, the multispecific antigen-binding molecule further comprises a third antigen-binding domain that binds to a tumor-associated antigen. In some embodiments, the tumor-associated antigen is a receptor expressed on prostate cancer cells or Ewing sarcoma. In some embodiments, the tumor-associated antigen is prostate-specific membrane antigen (PSMA), STEAP2, prostate stem cell antigen (PSCA), epithelial cell adhesion molecule (EpCAM), prostate-specific antigen (PSA), prostate acid phosphatase (PAP), or HBA-71.

[0045] In some embodiments, the multispecific antigen-binding molecule binds to human STEAP1, cynomolgus STEAP1, or a combination thereof, and preferably, the multispecific antigen-binding molecule binds to human STEAP1 of SEQ ID NO: 65.

[0046] In some embodiments, the first antigen-binding domain binds to at least one, at least two, at least three, at least four, or at least five residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1, and the residue positions 101, 102, 103, 195, 198, 202, and 281 correspond to the positions 101, 102, 103, 195, 198, 202, and 281 shown in SEQ ID NO: 65. In some embodiments, the first antigen-binding domain binds to Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1. In some embodiments, the heavy chain variable region of the first antigen-binding domain forms a hydrogen bond with at least one, at least two, at least three, at least four, or at least five residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1. In some embodiments, at least one, at least two, at least three, at least four, or at least five residues selected from Leu56, Ser73, Asn74, Gly101, Tyr103, and Tyr107 of the heavy chain variable region of the first antigen-binding domain form a hydrogen bond with at least one, at least two, at least three, at least four, or at least five residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1, and the residue positions of the heavy chain variable region of the first antigen-binding domain correspond to the positions 56, 73, 74, 101, 103, and 107 described in SEQ ID NO: 18.

[0047] In some embodiments, the first antigen-binding domain binds to at least one, at least two, or at least three residues selected from Gln201, Gln202, Asn203, and Lys204 of STEAP1, and the residue positions 201, 202, 203, and 204 correspond to the positions 201, 202, 203, and 204 shown in SEQ ID NO: 65. In some embodiments, the first antigen-binding domain binds to Gln201, Gln202, Asn203, and Lys204 of STEAP1. In some embodiments, the variable light chain region of the first antigen-binding domain forms a hydrogen bond with at least one residue selected from Gln201 and Gln202 of STEAP1. In some embodiments, at least one residue selected from Tyr53 and Tyr54 of the variable light chain region of the first antigen-binding domain forms a hydrogen bond with at least one residue selected from Gln201 and Gln202, and the residue positions of the variable light chain region of the first antigen-binding domain correspond to the positions 53 and 54 shown in SEQ ID NO: 18. In some embodiments, the residues of the variable light chain region of the first antigen-binding domain form van der Waals interactions with at least one residue selected from Asn203 and Lys204 of STEAP1.

[0048] In some embodiments, the multispecific antigen-binding molecule has a C of about 11, 11.5, 12, 12.6, 13, 13.5, 15, 18, 20, 23.4, 25, 27.9, 29.1, or 30 μg / mL max and has.

[0049] In some embodiments, the multispecific antigen-binding molecule has a C of about 11 μg / mL to about 30 μg / mL max and has.

[0050] In some embodiments, the multispecific antigen-binding molecule has a C of about 20 μg / mL to about 28 μg / mL max and has.

[0051] In some embodiments, the multispecific antigen-binding molecule has a C of about 24 μg / mL max and has.

[0052] In some embodiments, the multispecific antigen-binding molecule has an EC of about 0.6, 0.56, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.09, 0.05 or less. 50 It has.

[0053] In some embodiments, the multispecific antigen-binding molecule has an EC of about 0.05 to about 0.8. 50 It has.

[0054] In some embodiments, the EC 50 is determined in a 72-hour cell death assay using human CD8+ T cells and STEAP1-expressing LNCaP-X1.2 cells, and the EC 50 is from about 0.05 to about 0.4.

[0055] In some embodiments, the EC 50 is about 0.08 or about 0.3.

[0056] In some embodiments, the EC 50 is determined in a 72-hour cell death assay using human CD8+ T cells and STEAP1-expressing LNCaP X1.2KO3-13 cells, and the EC 50 is from about 0.1 to about 0.8.

[0057] In some embodiments, the EC 50 is about 0.1 or about 0.7.

[0058] In some embodiments, the multispecific antigen-binding molecule binds monovalently to STEAP1.

[0059] At least another aspect of the invention described herein is an antigen-binding molecule that binds to STEAP1, comprising a VH of an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2 and CDR-H3 selected from SEQ ID NOs: 7, 17-25, 30-34, 38 and 68; and an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2 and CDR-L3 of a VL sequence selected from SEQ ID NOs: 8, 26-29, 39 and 69.

[0060] At least another aspect of the invention described herein relates to an antigen-binding molecule that binds to STEAP1, comprising an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2 and CDR-H3; and an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2 and CDR-L3; CDR-H1 is Xaa 1 Xaa 2 comprises YMA (SEQ ID NO: 35); wherein Xaa 1 is Asp (D) or Asn (N); Xaa 2 is His (H), Tyr (Y), or Phe (F); CDR-H2 is YIXaa 3 YDGXaa 4 Xaa 5 TXaa 6 comprises YGDSVKG (SEQ ID NO: 36); wherein Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D) or Leu (L); Xaa 5 is Ser (S), Asp (D) or Asn (N); Xaa 6 is Ser (S) or Tyr (Y); CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); Xaa9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6.

[0061] In some embodiments, CDR-H1 comprises the amino acid sequence of SEQ ID NO: 10, 1, or 9. In some embodiments, CDR-H2 comprises the amino acid sequence of SEQ ID NO: 2, 11, 12, or 13. In some embodiments, CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15.

[0062] In some embodiments, the antigen-binding molecule comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 16; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0063] In some embodiments, the antigen-binding molecule comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0064] In some embodiments, the antigen-binding molecule comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 11; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0065] In some embodiments, the antigen-binding molecule comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0066] In some embodiments, the antigen-binding molecule comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14; a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0067] In some embodiments, the antigen-binding molecule comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 13; a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15; a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0068] In some embodiments, the antigen-binding molecule is a humanized antibody.

[0069] In some embodiments, the antigen-binding molecule comprises an IgG framework region and optionally comprises an IgG1 framework region.

[0070] In some embodiments, the antigen-binding molecule comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68.

[0071] In some embodiments, the antigen - binding molecule comprises an anti - STEAP1 light - chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 8, 26 - 29, 39 or 69.

[0072] In some embodiments, the antigen - binding molecule comprises an anti - STEAP1 heavy - chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 68, and an anti - STEAP1 light - chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 69.

[0073] In some embodiments, the antigen - binding molecule comprises an anti - STEAP1 heavy - chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 34, and an anti - STEAP1 light - chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 27.

[0074] In some embodiments, the antigen - binding molecule comprises an anti - STEAP1 heavy - chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 30, and an anti - STEAP1 light - chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 27.

[0075] In some embodiments, the antigen - binding molecule comprises an anti - STEAP1 heavy - chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 31, and an anti - STEAP1 light - chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 27.

[0076] In some embodiments, the antigen-binding molecule comprises a VH sequence of an anti-STEAP1 heavy chain variable region having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 32, and a VL sequence of an anti-STEAP1 light chain variable region having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 27.

[0077] In some embodiments, the antigen-binding molecule comprises a VH sequence of an anti-STEAP1 heavy chain variable region having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 33, and a VL sequence of an anti-STEAP1 light chain variable region having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 27.

[0078] In some embodiments, the antigen-binding molecule comprises an anti-STEAP1 heavy chain constant region sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 83, and an anti-STEAP1 light chain constant region sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 82.

[0079] In some embodiments, the antigen-binding molecule comprises an anti-STEAP1 heavy chain constant region sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 85, and an anti-STEAP1 light chain constant region sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 84.

[0080] In some embodiments, the antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 73 and an anti-STEAP1 light chain comprising SEQ ID NO: 72. In some embodiments, the antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 71 and an anti-STEAP1 light chain comprising SEQ ID NO: 70.

[0081] In some embodiments, the antigen-binding molecule is a full-length antibody or a fragment thereof.

[0082] In some embodiments, the antigen-binding molecule is a Fab, Fab’, F(ab’)2, Fv, Fd, single-chain Fv (scFv), trispecific (Fab3), bispecific (Fab2), diabody ((VL-VH)2 or (VH-VL)2), triabody (trivalent), tetrabody (tetravalent), minibody ((scFv-CH)2), bispecific single-chain Fv (Bis-scFv), IgGdeltaCH2, scFv-Fc, or (scFv)2-Fc.

[0083] In some embodiments, the antigen-binding molecule is a multispecific antibody, and preferably the antigen-binding molecule is a bispecific antibody or a trispecific antibody.

[0084] In some embodiments, the antigen-binding molecule further comprises an antigen-binding domain that binds to a T cell receptor. In some embodiments, the T cell receptor is cluster of differentiation 3 (CD3).

[0085] In some embodiments, the antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the amino acid sequences of SEQ ID NOs: 48-53.

[0086] In some embodiments, the antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 54, and an anti-CD3 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 55.

[0087] In some embodiments, the antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the amino acid sequences of SEQ ID NOs: 40-45.

[0088] In some embodiments, the antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 46, and an anti-CD3 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 47.

[0089] In some embodiments, the antigen-binding molecule further comprises an additional antigen-binding domain that binds to a tumor-associated antigen. In some embodiments, the tumor-associated antigen is a receptor expressed on prostate cancer cells or Ewing sarcoma. In some embodiments, the tumor-associated antigen is prostate-specific membrane antigen (PSMA), STEAP2, prostate stem cell antigen (PSCA), epithelial cell adhesion molecule (EpCAM), prostate-specific antigen (PSA), prostate acid phosphatase (PAP), or HBA-71.

[0090] In some embodiments, the antigen-binding molecule binds to human STEAP1, cynomolgus STEAP1, or a combination thereof, and preferably, the antigen-binding molecule binds to human STEAP1 of SEQ ID NO: 65.

[0091] In some embodiments, the antigen-binding molecule binds to at least one, at least two, at least three, at least four, or at least five residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1, and the residue positions 101, 102, 103, 195, 198, 202, and 281 correspond to the positions 101, 102, 103, 195, 198, 202, and 281 shown in SEQ ID NO: 65. In some embodiments, the antigen-binding molecule binds to Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1. In some embodiments, the heavy chain variable region of the antigen-binding molecule forms hydrogen bonds with at least one, at least two, at least three, at least four, or at least five residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1. In some embodiments, at least one, at least two, at least three, at least four, or at least five residues selected from Leu56, Ser73, Asn74, Gly101, Tyr103, and Tyr107 of the heavy chain variable region of the antigen-binding molecule form hydrogen bonds with at least one, at least two, at least three, at least four, or at least five residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1, and the residue positions of the heavy chain variable region of the antigen-binding molecule correspond to the positions 56, 73, 74, 101, 103, and 107 described in SEQ ID NO: 18.

[0092] In some embodiments, the antigen-binding molecule binds to at least one, at least two, or at least three residues selected from Gln201, Gln202, Asn203, and Lys204 of STEAP1, and residue positions 201, 202, 203, and 204 correspond to positions 201, 202, 203, and 204 shown in SEQ ID NO: 65. In some embodiments, the antigen-binding molecule binds to Gln201, Gln202, Asn203, and Lys204 of STEAP1. In some embodiments, the variable light chain region of the antigen-binding molecule forms a hydrogen bond with at least one residue selected from Gln201 and Gln202 of STEAP1. In some embodiments, at least one residue selected from Tyr53 and Tyr54 of the variable light chain region of the antigen-binding molecule forms a hydrogen bond with at least one residue selected from Gln201 and Gln202, and the residue positions of the variable light chain region of the antigen-binding molecule correspond to positions 53 and 54 shown in SEQ ID NO: 18. In some embodiments, the residues of the variable light chain region of the antigen-binding molecule form van der Waals interactions with at least one residue selected from Asn203 and Lys204 of STEAP1.

[0093] In some embodiments, the antigen-binding molecule binds monovalently to STEAP1.

[0094] At least another aspect of the invention described herein relates to an antibody comprising a first antigen-binding domain that binds to human STEAP1 at one or more residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281, and residue positions 101, 102, 103, 195, 198, 202, and 281 correspond to positions 101, 102, 103, 195, 198, 202, and 281 shown in SEQ ID NO: 65.

[0095] In some embodiments, the first antigen-binding domain binds to at least 1, at least 2, at least 3, at least 4, or at least 5 residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of SEQ ID NO: 65. In some embodiments, the first antigen-binding domain binds to Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of SEQ ID NO: 65. In some embodiments, the heavy-chain variable region of the first antigen-binding domain forms a hydrogen bond with at least 1, at least 2, at least 3, at least 4, or at least 5 residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1. In some embodiments, at least 1, at least 2, at least 3, at least 4, or at least 5 residues selected from Leu56, Ser73, Asn74, Gly101, Tyr103, and Tyr107 of the heavy-chain variable region of the first antigen-binding domain form a hydrogen bond with at least 1, at least 2, at least 3, at least 4, or at least 5 residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1, and the residue positions of the heavy-chain variable region of the first antigen-binding domain correspond to positions 56, 73, 74, 101, 103, and 107 described in SEQ ID NO: 18.

[0096] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 heavy-chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3 of a VH sequence selected from SEQ ID NOs: 7, 17-25, 30-34, 38, and 68; and an anti-STEAP1 light-chain variable region (VL) comprising three CDRs, CDR-L1, CDR-L2, and CDR-L3 of a VL sequence selected from SEQ ID NOs: 8, 26-29, 39, and 69.

[0097] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68.

[0098] In some embodiments, the first antigen-binding domain comprises an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69.

[0099] In some embodiments, the antibody further comprises a second antigen-binding domain that binds to a T cell receptor. In some embodiments, the T cell receptor is cluster of differentiation 3 (CD3).

[0100] In some embodiments, the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the amino acid sequences of SEQ ID NOs: 48-53.

[0101] In some embodiments, the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 54, and an anti-CD3 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 55.

[0102] In some embodiments, the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy-chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light-chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the amino acid sequences of SEQ ID NOs: 40-45.

[0103] In some embodiments, the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy-chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 46, and an anti-CD3 light-chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 47.

[0104] In some embodiments, the multispecific antigen-binding molecule further comprises a third antigen-binding domain that binds to a tumor-associated antigen. In some embodiments, the tumor-associated antigen is a receptor expressed on prostate cancer cells. In some embodiments, the tumor-associated antigen is prostate-specific membrane antigen (PSMA), STEAP2, prostate stem cell antigen (PSCA), epithelial cell adhesion molecule (EpCAM), prostate-specific antigen (PSA), or prostate acid phosphatase (PAP).

[0105] At least another aspect of the invention described herein relates to one or more isolated nucleic acids encoding, individually or together, the multispecific antigen-binding molecules described herein, the antigen-binding molecules described herein, or the antibodies described herein.

[0106] At least another aspect of the invention described herein relates to one or more vectors comprising, individually or together, one or more of the isolated nucleic acids described herein.

[0107] At least another aspect of the invention described herein relates to one or more host cells that individually or together contain one or more of the isolated nucleic acids described herein or one or more of the vectors described herein. In some embodiments, the host cell is a mammalian cell. In some embodiments, the mammalian cell is a Chinese hamster ovary (CHO) cell. In some embodiments, the host cell is an insect cell. In some embodiments, the host cell is a prokaryotic cell.

[0108] At least another aspect of the invention described herein relates to a method for producing a multispecific antigen-binding molecule described herein, an antigen-binding molecule described herein, or an antibody described herein, comprising culturing one or more of the host cells described herein in a culture medium. In some embodiments, the method further comprises harvesting a multispecific antigen-binding molecule described herein, an antigen-binding molecule described herein, or an antibody described herein from one or more host cells or the culture medium.

[0109] At least another aspect of the invention described herein relates to a pharmaceutical composition comprising a multispecific antigen-binding molecule described herein, an antigen-binding molecule described herein, or an antibody described herein. In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, excipient, or diluent.

[0110] In some embodiments, the pharmaceutical composition is for use as a medicament. In some embodiments, the pharmaceutical composition is for use in the treatment or delay of progression of STEAP1-expressing cancer. In some embodiments, the pharmaceutical composition is for use in the treatment or delay of progression of prostate cancer or Ewing's sarcoma.

[0111] At least another aspect of the invention described herein relates to the use of a multispecific antigen-binding molecule, an antigen-binding molecule, or an antibody described herein for the treatment or delay of progression of STEAP1-expressing cancer in a subject in need thereof for the treatment or delay of progression of STEAP1-expressing cancer.

[0112] At least another aspect of the invention described herein relates to the use of a multispecific antigen-binding molecule, an antigen-binding molecule, or an antibody described herein for inhibiting or reducing the growth of STEAP1-expressing cancer cells.

[0113] In some embodiments, the STEAP1-expressing cancer is a solid tumor.

[0114] In some embodiments, the STEAP1-expressing cancer is prostate cancer or Ewing sarcoma.

[0115] In some embodiments, the multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody described herein is used in combination with an additional therapeutic agent or an additional treatment regimen.

[0116] In some embodiments, the additional therapeutic agent includes a chemotherapeutic agent, an immunotherapeutic agent, a targeted therapy, radiation therapy, or a combination thereof.

[0117] In some embodiments, the additional therapeutic agent includes a first-line, second-line, or third-line therapy.

[0118] In some embodiments, the additional treatment regimen includes surgery.

[0119] In some embodiments, the multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody described herein and the additional therapeutic agent are administered simultaneously.

[0120] In some embodiments, the multispecific antigen-binding molecules described herein, the antigen-binding molecules described herein, or the antibodies and additional therapeutic agents described herein are administered sequentially.

[0121] In some embodiments, the multispecific antigen-binding molecules described herein, the antigen-binding molecules described herein, or the antibodies described herein are administered first before administering an additional therapeutic agent.

[0122] In some embodiments, the multispecific antigen-binding molecules described herein, the antigen-binding molecules described herein, or the antibodies described herein are administered after administering an additional therapeutic agent.

[0123] In some embodiments, the multispecific antigen-binding molecules described herein, the antigen-binding molecules described herein, or the antibodies described herein are administered systemically.

[0124] In some embodiments, the multispecific antigen-binding molecules described herein, the antigen-binding molecules described herein, or the antibodies described herein are administered locally.

[0125] In some embodiments, the multispecific antigen-binding molecules described herein, the antigen-binding molecules described herein, or the antibodies described herein are administered parenterally.

[0126] In some embodiments, the multispecific antigen-binding molecules described herein, the antigen-binding molecules described herein, or the antibodies described herein are administered intravenously or subcutaneously.

[0127] In some embodiments, the subject is human.

[0128] At least another aspect of the invention described herein relates to the use of a multispecific antigen-binding molecule, an antigen-binding molecule, or an antibody described herein in the manufacture of a medicament for treating STEAP1-expressing cancer or, optionally, for treating prostate cancer or Ewing sarcoma or delaying the progression thereof.

[0129] At least another aspect of the invention described herein relates to the use of a multispecific antigen-binding molecule, an antigen-binding molecule, or an antibody described herein in the manufacture of a medicament for inhibiting or reducing the proliferation of STEAP1-expressing cancer cells, optionally prostate cancer cells or Ewing sarcoma cells.

[0130] At least another aspect of the invention described herein relates to a method for treating or delaying the progression in a subject in need thereof of STEAP1-expressing cancer, the method comprising administering to the subject an effective amount of a multispecific antigen-binding molecule, an antigen-binding molecule, or an antibody described herein.

[0131] In some embodiments, the STEAP1-expressing cancer is a solid tumor. In some embodiments, the STEAP1-expressing cancer is prostate cancer or Ewing sarcoma.

[0132] In some embodiments, the method further comprises administering to the subject an additional therapeutic agent or an additional therapeutic regimen. In some embodiments, the additional therapeutic agent comprises a chemotherapeutic agent, an immunotherapeutic agent, a targeted therapy, radiation therapy, or a combination thereof. In some embodiments, the additional therapeutic agent comprises a first-line, second-line, or third-line therapy. In some embodiments, the additional therapeutic regimen comprises surgery.

[0133] In some embodiments, the additional therapeutic agent is administered concurrently with the multispecific antigen-binding molecule described herein, the antigen-binding molecule described herein, or the antibody described herein.

[0134] In some embodiments, the additional therapeutic agent is administered sequentially with the multispecific antigen-binding molecule described herein, the antigen-binding molecule described herein, or the antibody described herein.

[0135] In some embodiments, the multispecific antigen-binding molecule described herein, the antigen-binding molecule described herein, or the antibody described herein is administered first, prior to administration of the additional therapeutic agent.

[0136] In some embodiments, the multispecific antigen-binding molecule described herein, the antigen-binding molecule described herein, or the antibody described herein is administered after administration of the additional therapeutic agent.

[0137] In some embodiments, the multispecific antigen-binding molecule described herein, the antigen-binding molecule described herein, or the antibody described herein is administered systemically. In some embodiments, the multispecific antigen-binding molecule described herein, the antigen-binding molecule described herein, or the antibody described herein is administered locally. In some embodiments, the multispecific antigen-binding molecule described herein, the antigen-binding molecule described herein, or the antibody described herein is administered parenterally. In some embodiments, the multispecific antigen-binding molecule described herein, the antigen-binding molecule described herein, or the antibody described herein is administered intravenously or subcutaneously.

[0138] In some embodiments, the subject is human.

[0139] At least another aspect of the invention described herein is a method of inhibiting or reducing the proliferation of STEAP1-expressing cells, the method comprising contacting the cells with a multispecific antigen-binding molecule described herein, an antigen-binding molecule described herein, or an antibody described herein for a time sufficient to inhibit the proliferation of the cells.

[0140] In some embodiments, the cells are prostate cancer cells or Ewing's sarcoma cells. In some embodiments, the method is an in vivo method. In some embodiments, the method is an in vitro or ex vivo method.

[0141] At least another aspect of the invention described herein is a kit comprising a multispecific antigen-binding molecule described herein, an antigen-binding molecule described herein, an antibody described herein, one or more isolated nucleic acids described herein, one or more vectors described herein, one or more host cells described herein, or a pharmaceutical composition described herein, optionally comprising a set of instructions. BRIEF DESCRIPTION OF THE DRAWINGS

[0142]

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Mode for Carrying Out the Invention

[0143] Detailed Description I. Definitions As used herein, the term "about" refers to the normal error range of each value, which can be easily understood by those skilled in the art of this technology. References to a value or parameter following "about" in this specification include (and describe) embodiments directed to the value or parameter itself.

[0144] "Affinity" refers to the total strength of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless otherwise indicated, as used herein, "binding affinity" refers to the intrinsic binding affinity that reflects a 1:1 interaction between the moieties of a binding pair (e.g., an antibody and an antigen). The affinity of molecule X for its partner Y can generally be represented by the equilibrium dissociation constant (K D ). Affinity can be measured by common methods known in the art, including the methods described herein. Specific illustrative and exemplary embodiments for measuring binding affinity are described below.

[0145] As used herein, the term "bind" refers to a measurable and reproducible interaction, such as that between a target and an antigen-binding molecule (e.g., an antibody), which determines the presence of the target in the presence of a heterogeneous population of molecules, including biomolecules. For example, an antigen-binding molecule that specifically binds to a target (which may be an epitope) binds the target with higher affinity, binding activity, more readily, and / or for a longer period than an antigen-binding molecule that binds to other targets. In one embodiment, the degree of binding of the antigen-binding molecule to an irrelevant target is less than about 10% of the binding of the antigen-binding molecule to the target, as measured, for example, by surface plasmon resonance (SPR), radioimmunoassay (RIA), or kinetic exclusion assay (KinExA®). In certain embodiments, an antigen-binding molecule that specifically binds to a target has an equilibrium dissociation constant (K D ) of ≦1 μM, ≦100 nM, ≦10 nM, ≦1 nM, or ≦0.1 nM. In certain embodiments, the antigen-binding molecule specifically binds to an epitope on a protein that is conserved between proteins from different species. In another embodiment, specific binding can include, but does not require, exclusive binding.

[0146] As used herein, the term "antigen-binding molecule" refers to a molecule that specifically binds to a target epitope, antigen, ligand, or receptor. Antigen-binding molecules include, but are not limited to, antibodies (e.g., monoclonal, polyclonal, recombinant, humanized, and chimeric antibodies), antibody fragments or portions thereof (e.g., Fab fragments, Fab'2, scFv antibodies, SMIPs, domain antibodies, diabodies, minibodies, scFv-Fc, affibodies, nanobodies, and VH domains and / or VL domains of antibodies), receptors, ligands, aptamers, and other molecules having a defined binding partner. An "affinity matured" antibody refers to an antibody having one or more alterations in one or more complementarity determining regions (CDRs) or hypervariable regions (HVRs), and such alterations result in an improvement in the affinity of the antibody for the antigen as compared to the parental antibody that does not have such alterations.

[0147] The term "antigen-binding domain" refers to a compound or part of a molecule that specifically binds to a target epitope, antigen, ligand, or receptor. Molecules characterized by an antigen-binding domain include antibodies (e.g., monoclonal, polyclonal, recombinant, humanized, and chimeric antibodies), antibody fragments or parts thereof (e.g., Fab fragments, Fab’2, scFv antibodies, SMIP, domain antibodies, diabodies, minibodies, scFv-Fc, affibodies, nanobodies, and the VH and / or VL domains of antibodies), receptors, ligands, aptamers, and other molecules having an identified binding partner, but are not limited thereto.

[0148] The term "antibody" as used herein is used in the broadest sense and includes various antibody structures, including, but not limited to, monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific or trispecific antibodies), and antibody fragments, as long as they exhibit the desired antigen-binding activity.

[0149] "Antibody fragment" refers to a molecule other than an intact antibody that includes a portion of an intact antibody that binds an antigen to which the intact antibody binds. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab’, Fab’-SH, F(ab’)2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv and scFab); single domain antibodies (dAb), and multispecific antibodies formed from antibody fragments. For an overview of specific antibody fragments, see Holliger and Hudson, Nat. Biotech. 23:1126-1136 (2005).

[0150] A "single-chain variable fragment" or "scFv" is a fusion protein of the variable domains of the heavy (VH) and light (VL) chains of an antibody, linked by a linker. In particular, the linker is typically a short polypeptide of 10 to 25 amino acids, usually rich in glycine for flexibility and rich in serine or threonine for solubility, and it is possible to link the N-terminus of VH to the C-terminus of VL or vice versa. This protein retains the specificity of the original antibody despite removal of the constant regions and introduction of the linker. For a review of scFv fragments, see, for example, Plueckthun, The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenberg and Moore eds., (Springer-Verlag, New York), pp. 269-315 (1994). See also WO 93 / 16185, as well as U.S. Pat. Nos. 5,571,894 and 5,587,458.

[0151] A "single-chain Fab fragment" or "scFab" is a polypeptide consisting of the variable domain of the antibody heavy chain (VH), the constant domain 1 of the antibody heavy chain (CH1), the variable domain of the antibody light chain (VL), the constant domain of the antibody light chain (CL), and a linker, and the antibody domains and the linker are in the following order from the N-terminus to the C-terminus: a) VH-CH1-linker-VL-CL, b) VL-CL-linker-VH-CH1, c) VH-CL-linker-VL-CH1, or d) VL-CH1-linker-VH-CL. In particular, the linker is a polypeptide of at least 30 amino acids, preferably 32 to 50 amino acids. The single-chain Fab fragment is stabilized by the native disulfide bond between the CL domain and the CH1 domain. In addition, these single-chain Fab fragments will be further stabilized by the formation of interchain disulfide bonds by insertion of cysteine residues (e.g., positions 44 of the variable heavy chain and 100 of the variable light chain according to Kabat numbering).

[0152] The term "cross-Fab fragment" or "xFab fragment" or "crossover Fab fragment" refers to a Fab fragment in which either the variable or constant region of the heavy and light chains has been exchanged. A cross Fab fragment includes a polypeptide chain composed of a light chain variable region (VL) and a heavy chain constant region 1 (CH1), and a polypeptide chain composed of a heavy chain variable region (VH) and a light chain constant region (CL). The asymmetric Fab arms can also be engineered by introducing charged or uncharged amino acid mutations at the domain interface to direct correct Fab pairing. See, for example, International Publication No. WO 2016 / 172485.

[0153] The term "antigen" refers to a proteinaceous or non-proteinaceous molecule to which an antigen-binding molecule (e.g., an antibody) binds. An antigen can include a protein, a protein fragment, or a hapten.

[0154] The term "epitope" refers to a site on either a proteinaceous or non-proteinaceous antigen to which an anti-STEAP1 antigen-binding molecule (e.g., an anti-STEAP1 antibody) binds. Epitopes can be formed from either contiguous stretches of amino acids (linear epitopes) or can contain non-contiguous amino acids (conformational epitopes), e.g., formed by the folding of the antigen (i.e., by the tertiary folding of a proteinaceous antigen) such that they are spatially proximate. Linear epitopes typically remain bound by an anti-STEAP1 antigen-binding molecule even after exposure of the proteinaceous antigen to a denaturing agent, whereas conformational epitopes are typically disrupted by treatment with a denaturing agent. An epitope contains at least 3, at least 4, at least 5, at least 6, at least 7, or 8-10 amino acids in a unique spatial conformation.

[0155] The screening of antigen-binding molecules (e.g., antibodies) that bind to a specific epitope (i.e., antibodies that bind to the same epitope) can be performed, for example, but not limited to, alanine scanning, peptide blotting (see Meth. Mol. Biol. 248 (2004) 443-463), peptide cleavage analysis, epitope excision, epitope extraction, chemical modification of the antigen (see Prot. Sci. 9 (2000) 487-496), and cross-blocking (see "Antibodies", Harlow and Lane (Cold Spring Harbor Press, Cold Spring Harbor, NY)), using methods conventional in the art.

[0156] Antigen Structure-based Antibody Profiling (ASAP), also known as Modification-Assisted Profiling (MAP), can bin a number of monoclonal antibodies that specifically bind to STEAP1 based on the respective binding profiles of a number of antibodies to a chemically or enzymatically modified antigen surface (see, for example, US 2004 / 0101920). The antibodies in each bin bind to the same epitope, which may be a unique epitope that is clearly different from or partially overlapping with the epitope represented by another bin.

[0157] Furthermore, competitive binding can be used to readily determine whether an antigen-binding molecule (e.g., an antibody) binds to the same epitope of STEAP1 as a reference anti-STEAP1 antibody or competes with it for binding. For example, an “antigen-binding molecule that binds to the same epitope” as the reference anti-STEAP1 antibody refers to an antigen-binding molecule that blocks 50% or more of the binding of the reference anti-STEAP1 antibody to its antigen in a competition assay. Conversely, the reference antibody blocks 50% or more of the binding of the antigen-binding molecule to its antigen in a competition assay. Also, for example, to determine whether an antigen-binding molecule binds to the same epitope as the reference anti-STEAP1 antibody, the reference antibody is bound to STEAP1 under saturation conditions. After removing the excess reference anti-STEAP1 antibody, the ability of the anti-STEAP1 antigen-binding molecule in question to bind to STEAP1 is evaluated. If the anti-STEAP1 antigen-binding molecule in question can bind to STEAP1 after saturation binding of the reference anti-STEAP1 antibody, it can be concluded that the anti-STEAP1 antigen-binding molecule in question binds to a different epitope than the reference anti-STEAP1 antibody. However, if the anti-STEAP1 antigen-binding molecule in question cannot bind to STEAP1 after saturation binding of the reference anti-STEAP1 antibody, the anti-STEAP1 antigen-binding molecule in question may bind to the same epitope as the epitope to which the reference anti-STEAP1 antibody binds. Conventional experiments can be used to confirm whether the antigen-binding molecule in question binds to the same epitope or is only sterically hindered from binding (e.g., peptide mutagenesis, ELISA, RIA, surface plasmon resonance, flow cytometry, or binding analysis using other quantitative or qualitative antibody-binding assays available in the art). This assay can be performed in two setups, i.e., with both molecules being saturating antibodies. In both settings, if only the first (saturating) antibody can bind to STEAP1, it can be concluded that the anti-STEAP1 antigen-binding molecule in question and the reference anti-STEAP1 antibody compete for binding to STEAP1.

[0158] The term "STEAP1" refers to any STEAP1 derived from any vertebrate source, including mammals such as primates (e.g., humans or non-human primates) and rodents (e.g., mice and rats). This term encompasses "full-length" STEAP1 and naturally occurring variants of STEAP1, including, for example, splice variants or allelic variants. STEAP1 is a member of the six-transmembrane epithelial antigen of the prostate (STEAP) protein family. The STEAP protein family includes five members, STEAP1, STEAP2, STEAP3, STEAP4, and STEAP5. STEAP1, STEAP2, and STEAP4 have been observed to be overexpressed in different cancer cells but minimally expressed in normal tissues. Examples of STEAP1 include human STEAP1 (UniProtKB accession number: Q9UHE8-1; SEQ ID NO: 65), cynomolgus monkey STEAP1 (UniProtKB accession number: A0A2K5X1J3; SEQ ID NO: 66), and orangutan STEAP1 (UniProtKB accession number: H2PMZ0; SEQ ID NO: 67).

[0159] The following is an exemplary amino acid sequence of human STEAP1. MESRKDITNQEELWKMKPRRNLEEDDYLHKDTGETSMLKRPVLLHLHQTAHADEFDCPSELQHTQELFPQWHLPIKIAAIIASLTFLYTLLREVIHPLATSHQQYFYKIPILVINKVLPMVSITLLALVYLPGVIAAIVQLHNGTKYKKFPHWLDKWMLTRKQFGLLSFFFAVLHAIYSLSYPMRRSYRYKLLNWAYQQVQQNKEDAWIEHDVWRMEIYVSLGIVGLAILALLAVTSIPSVSDSLTWREFHYIQSKLGIVSLLLGTIHALIFAWNKWIDIKQFVWYTPPTFMIAVFLPIVVLIFKSILFLPCLRKKILKIRHGWEDVTKINKTEICSQL (SEQ ID NO: 65).

[0160] The following is an exemplary amino acid sequence of STEAP1 from cynomolgus monkey (Macaca fascicularis). MESRKDITNEEELWKMKPRRNLEEDDYLHKDTGETSMLKRPVLLHLHQTAHADEFDCPSELQHTQELFPQWHLPIKIAAIIASLTFLYTLLREVIHPLATSHQQYFYKIPILVINKVLPMVSITLLALVYLPGVIAAIVQLHNGTKYKKFPHWLDKWMLTRKQFGLLSFFFAVLHAIYSLSYPMRRSYRYKLLNWAYQQVQQNKEDAWIEHDVWRMEIYVSLGIVGLAILALLAVTSIPSVSDSLTWREFHYIQSKLGIVSLLLATIHALIFAWNKWIDIKQFVWYTPPTFMIAVFLPVVVLIFKSILFLPCLRKKILKIRHGWEDVTKINKMEISSQL (SEQ ID NO: 66).

[0161] The following is an exemplary amino acid sequence of STEAP1 from orangutan (Pongo abelii). MESRKDITNQEELWKMKPRRNLEEDDYLHKDTGETSMLKRPVLLHLHQTAHADEFDCPSELQQTRELFPQWHLPIKIAAIIASLTFLYTLLREVIHPLATSHQQYFYKIPILVINKVLPMVSITLLALVYLPGVIAAIVQLHNGTKYKKFPHWLDKWMLTRKQFGLLSFFFAVLHAIYSLSYPMRRSYRYKLLNWAYQQVQQNKEDAWIEHDVWRMEIYVSLGIVGLAILALLAVTSIPSVSDSLTWREFHYIQSKLGIVSLLLGTIHALIFAWNKWIDIKQFVWYTPPTFMIAVILPIVVLIFKSILFLPCLRKKILKIRHGWEDVTKINKTEISSQL (SEQ ID NO: 67).

[0162] The term "anti-STEAP1 antigen-binding molecule" or "antigen-binding molecule that binds to STEAP1" refers to any molecule that can bind to STEAP1 with sufficient affinity such that the molecule is useful as a diagnostic and / or therapeutic agent in the targeting of STEAP1. In one embodiment, the degree of binding of the anti-STEAP1 antigen-binding molecule to an irrelevant non-STEAP1 protein is less than about 10% of the binding of the antigen-binding molecule to STEAP1, as measured, for example, by surface plasmon resonance (SPR), radioimmunoassay (RIA), or kinetic exclusion assay (KinExA®). In certain embodiments, the anti-STEAP1 antigen-binding molecule has a dissociation constant (K -8 d) of ≤1 μM, ≤100 nM, ≤10 nM, ≤1 nM, ≤0.1 nM, ≤0.01 nM, or ≤0.001 nM (e.g., 10 -8 M or less, e.g., 10 -13 M to 10 -9 M, e.g., 10 -13 M to 10- D M). An antigen-binding molecule is said to "specifically bind" to STEAP1 if it has a K D of 1 μM or less. In certain embodiments, the anti-STEAP1 antigen-binding molecule binds to an epitope of STEAP1 that is conserved among STEAPs from different species.

[0163] The term "anti-STEAP1 antibody" or "antibody that binds to STEAP1" refers to an antibody that can bind to STEAP1 with sufficient affinity such that the antibody is useful as a diagnostic and / or therapeutic agent in the targeting of STEAP1. In one embodiment, the degree of binding of the anti-STEAP1 antibody to an irrelevant non-STEAP1 protein is less than about 10% of the binding of the antibody to STEAP1, as measured, for example, by surface plasmon resonance (SPR), radioimmunoassay (RIA), or kinetic exclusion assay (KinExA®). In certain embodiments, the anti-STEAP1 antibody has a dissociation constant of ≤1 μM, ≤100 nM, ≤10 nM, ≤1 nM, ≤0.1 nM, ≤0.01 nM, or ≤0.001 nM (e.g., 10 -8 M or less, e.g., 10 -8 M to 10 -13 M, e.g., 10-9 M~10 -13 The dissociation constant (K D ) of M). When the antibody has a K of 1 μM or less D , the antibody is said to "specifically bind" to STEAP1. In certain embodiments, the anti-STEAP1 antibody binds to an epitope of STEAP1 that is conserved among STEAPs from different species.

[0164] The term "cluster of differentiation 3" or "CD3" as used herein refers to any native CD3 from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats), unless otherwise indicated, and includes, for example, the CD3ε, CD3γ, CD3α, and CD3β chains. This term encompasses "full-length" unprocessed CD3 (e.g., unprocessed or unmodified CD3ε or CD3γ), as well as any form of CD3 obtained from intracellular processing. This term also encompasses naturally occurring variants of CD3, including, for example, splice variants or allelic variants. CD3 includes, for example, the human CD3ε protein that is 207 amino acids in length (NCBI reference sequence number NP_000724), and the human CD3γ protein that is 182 amino acids in length (NCBI reference sequence number NP_000064).

[0165] The terms "anti-CD3 antibody" and "antibody that binds CD3" refer to an antibody that can bind to CD3 with sufficient affinity such that the antibody is useful as a diagnostic and / or therapeutic agent in the targeting of CD3. In one embodiment, the degree of binding of the anti-CD3 antibody to an irrelevant non-CD3 protein is less than about 10% of the binding of the antibody to CD3, as measured, for example, by surface plasmon resonance (SPR), radioimmunoassay (RIA), or kinetic exclusion assay (KinExA®). In certain embodiments, the antibody that binds CD3 has a Kd of ≦1 μM, ≦100 nM, ≦10 nM, ≦1 nM, ≦0.1 nM, ≦0.01 nM, or ≦0.001 nM (e.g., 10 -8 M or less, e.g., 10 -8 ~10-13 M, for example 10 -9 M to 10 -13 dissociation constant (K D ) having. In certain embodiments, the anti-CD3 antibody binds to an epitope of CD3 that is conserved among CD3s from different species. In some embodiments, the anti-CD3 antibody is described in International Patent Application Publication No. 2015 / 095392, which is incorporated herein by reference in its entirety. In some embodiments, the anti-CD3 antibody is described in U.S. Patent No. 10,174,124, which is incorporated herein by reference in its entirety. In other embodiments, the anti-CD3 antibody is described in International Patent Application No. PCT / US2020 / 064635, which is incorporated herein by reference in its entirety.

[0166] In some embodiments, the anti-CD3 antibody is 40G5c. In some embodiments, the anti-CD3 antibody is 38E4V1.MD1. The sequence numbers of the CDRs of 40G5c and 38E4V1.MD1 and the VH and VL sequences are listed in Tables 1 and 2.

[0167] In some aspects, when a 1-, 5-, 10-, 20- or 100-fold excess of one antibody inhibits the binding of the other by at least 50%, at least 75%, at least 90%, or even 99% or more as measured by a competitive binding assay, the two antibodies are considered to bind to the same or overlapping epitopes (see, for example, Junghans et al., Cancer Res. 50 (1990) 1495-1502).

[0168] In some aspects, when substantially all amino acid mutations in an antigen that reduce or eliminate the binding of one antibody also reduce or eliminate the binding of the other antibody, the two antibodies are considered to bind to the same epitope. Two antibodies are considered to have "overlapping epitopes" when only a subset of the amino acid mutations that reduce or eliminate the binding of one antibody also reduce or eliminate the binding of the other antibody.

[0169] The term "chimeric" antibody refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species and the remaining portion of the heavy and / or light chain is derived from a different source or species.

[0170] The "class" of an antibody refers to the type of constant domain or constant region carried by its heavy chain. Antibodies have five main classes: IgA, IgD, IgE, IgG, and IgM, some of which can be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. In certain embodiments, the antibody is of the IgG1 isotype. In certain embodiments, the antibody is of the IgG1 isotype having the P329G, L234A, and L235A mutations to reduce Fc region effector function. In other embodiments, the antibody is of the IgG2 isotype. In certain embodiments, the antibody is of the IgG4 isotype having the S228P mutation in the hinge region to improve the stability of the IgG4 antibody. The heavy chain constant domains corresponding to the different classes of immunoglobulins are called α, δ, ε, γ, and μ, respectively. The light chain of an antibody can be assigned to one of two types called kappa (κ) and lambda (λ) based on the amino acid sequence of its constant domain.

[0171] As used herein, the term "hypervariable region" or "HVR" refers to each region of the antibody variable domain where the sequence is hypervariable and determines antigen-binding specificity, e.g., "complementary determining regions" (CDRs).

[0172] Generally, an antibody contains six CDRs, three in VH (CDR-H1, CDR-H2, CDR-H3) and three in VL (CDR-L1, CDR-L2, CDR-L3). Exemplary CDRs herein include the following: (a) Hypervariable loops occurring at amino acid residues 26 - 32 (L1), 50 - 52 (L2), 91 - 96 (L3), 26 - 32 (H1), 53 - 55 (H2), and 96 - 101 (H3) (Chothia and Lesk, J. Mol. Biol. 196:901 - 917 (1987)), (b) CDRs present at amino acid residues 24 - 34 (L1), 50 - 56 (L2), 89 - 97 (L3), 31 - 35b (H1), 50 - 65 (H2) and 95 - 102 (H3) (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991)); and (c) Antigen contacts occurring at amino acid residues 27c - 36 (L1), 46 - 55 (L2), 89 - 96 (L3), 30 - 35b (H1), 47 - 58 (H2) and 93 - 101 (H3) (MacCallum et al. J. Mol. Biol. 262:732 - 745 (1996)).

[0173] Unless otherwise indicated, CDRs are determined according to Kabat et al. above. One of ordinary skill in the art will understand that the CDR designations can also be determined according to Chothia above, MacCallum above, or any other scientifically recognized nomenclature.

[0174] The term "variable region" or "variable domain" refers to the domain of an antibody heavy or light chain that is involved in binding of the antibody to an antigen. The variable domains of the heavy and light chains of a native antibody (VH and VL, respectively) generally have similar structures, and each domain contains four conserved framework regions (FRs) and three complementarity - determining regions (CDRs) or hypervariable regions (HVRs). (e.g., Kindt et al. Kuby Immunology, 6 th(see, e.g., 5th ed., W.H.Freeman and Co., 91 pages (2007)). A single VH or VL domain may be sufficient to confer antigen-binding specificity. Further, an antibody that binds a particular antigen can be isolated using the VH domain or VL domain of an antibody that binds that antigen, and libraries of complementary VL domains or VH domains, respectively, can be screened. See, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991).

[0175] "Human-derived constant region" or "human constant region" refers to the constant heavy chain region of a human antibody of subclass IgG1, IgG2, IgG3, or IgG4, and / or the constant light chain kappa or lambda region. Such constant regions are known in the art and are described, for example, in Kabat, E.A., et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD (1991) (see also, e.g., Johnson and Wu, Nucleic Acids Res. 28 (2000) 214-218; Kabat et al., Proc. Natl. Acad. Sci. USA 72 (1975) 2785-2788). Unless otherwise specified herein, the numbering of amino acid residues in the constant regions follows the EU numbering system (also referred to as the Kabat EU index) as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD (1991), NIH Publication 91-3242.

[0176] The terms "Fc region" or "Fc domain" are used interchangeably herein and refer to the C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. This term includes native sequence Fc regions and variant Fc regions. In one embodiment, the human IgG heavy chain Fc region extends from Cys226 or Pro230 to the carboxyl terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. This term includes cleaved Fc regions, e.g., those having a C-terminal cleavage (e.g., ΔGK cleavage, as described in, e.g., Hu et al., Biotechnol. Prog. 2017, 33:786-794 and Jiang et al., J. Pharm. Sci. 2016, 105:2066-2072). Unless otherwise specified herein, the numbering of amino acid residues in the Fc region or constant region follows the EU numbering scheme (also referred to as the EU index) as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. As used herein, a "subunit" of an Fc domain refers to one of the two polypeptides that form a dimeric Fc domain, i.e., a polypeptide that includes the C-terminal constant region of an immunoglobulin heavy chain and has the ability to self-associate stably. In one embodiment, the subunit of an IgG Fc domain includes the IgG CH2 and IgG CH3 constant regions.

[0177] "Framework" or "FR" refers to variable domain residues other than complementarity determining region (CDR) or hypervariable region (HVR) residues. The FRs of a variable domain generally consist of four FR domains: FR1, FR2, FR3, and FR4. Thus, CDR and FR sequences generally appear in the following order in VH (or VL): FR1-CDR-H1(CDR-L1)-FR2-CDR-H2(CDR-L2)-FR3-CDR-H3(CDR-L3)-FR4.

[0178] The terms "full-length antibody", "intact antibody", and "whole antibody" are used interchangeably herein to refer to an antibody having a structure substantially similar to that of a native antibody or having a heavy chain that contains an Fc region as defined herein.

[0179] "Human antibody" refers to an antibody produced by a human or human cell, or an antibody having an amino acid sequence corresponding to a non-human-derived antibody that utilizes a sequence encoding a human antibody such as a human antibody repertoire. This definition of human antibody specifically excludes humanized antibodies that contain non-human antigen-binding residues. Human antibodies can be produced using a variety of techniques known in the art, including phage display libraries. Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991). The methods described in Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boerner et al., J. Immunol., 147(1):86-95 (1991) are also available for the preparation of human monoclonal antibodies. See also van Dijk and van de Winkel, Curr. Opin. Pharmacol., 5:368-74 (2001). Human antibodies can be prepared by administering an antigen to a transgenic animal whose endogenous locus has been inactivated but that has been modified to produce such antibodies in response to antigen exposure, e.g., an immunized xenomouse (see, e.g., U.S. Pat. Nos. 6,075,181 and 6,150,584 regarding XENOMOUSE™ technology). See, e.g., Li et al., Proc. Natl. Acad. Sci. USA, 103:3557-3562 (2006) regarding human antibodies generated via human B cell hybridoma technology.

[0180] The "human consensus framework" is a framework that represents the most commonly occurring amino acid residues in the selection of human immunoglobulin VL or VH framework sequences. Generally, the selection of human immunoglobulin VL or VH sequences is from a subgroup of variable domain sequences. Generally, the subgroup of sequences is the subgroup described in Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, NIH Publication 91-3242, Bethesda MD (1991), vols. 1-3. In one embodiment, for VL, the subgroup is subgroup kappa I in Kabat et al. (supra). In one embodiment, for VH, the subgroup is subgroup III in Kabat et al. (supra).

[0181] A "humanized" antibody refers to a chimeric antibody that contains amino acid residues derived from non-human CDRs or HVRs and amino acid residues derived from human FRs. In certain embodiments, a humanized antibody comprises substantially all of at least one, typically two, variable domains, with all or substantially all of the CDRs or HVRs corresponding to the CDRs or HVRs of a non-human antibody and all or substantially all of the FRs corresponding to the FRs of a human antibody. A humanized antibody may optionally comprise at least a portion of an antibody constant region derived from a human antibody. The "humanized form" of an antibody, e.g., a non-human antibody, refers to the antibody that has been humanized.

[0182] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous population of antibodies, i.e., the individual antibodies comprising the population are identical and / or bind to the same epitope, except for variant antibodies that may be present, for example, as a result of naturally occurring mutations or that may arise during the production of a monoclonal antibody preparation, and such variants are generally present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, the modifier "monoclonal" indicates the character of an antibody obtained from a substantially homogeneous collection of antibodies and should not be construed as requiring production of the antibody by any particular method. For example, monoclonal antibodies used in accordance with the present invention may be made by a variety of techniques including, but not limited to, the hybridoma method, recombinant DNA methods, phage display methods, and methods utilizing transgenic animals that contain all or part of the human immunoglobulin loci, and such methods and other exemplary methods for making monoclonal antibodies are described herein.

[0183] As used herein, the term "monospecific" refers to an antigen-binding molecule that binds to a single antigen, e.g., STEAP1. As used herein, the term "multispecific" refers to an antigen-binding molecule that binds to multiple different antigens, e.g., STEAP1 and CD3. For example, a "multispecific antibody" is a monoclonal antibody that has binding specificities for at least two different sites, i.e., different epitopes on different antigens or different epitopes on the same antigen.

[0184] "Native antibody" refers to naturally occurring immunoglobulin molecules having various structures. For example, native IgG antibodies are approximately 150,000 Dalton heterotetrameric glycoproteins composed of two identical light chains and two identical heavy chains that are disulfide-bonded. Each heavy chain from the N-terminus to the C-terminus has a variable region (VH), also called the variable heavy domain or heavy chain variable domain, followed by three constant domains (CH1, CH2, and CH3). Similarly, from the N-terminus to the C-terminus, each light chain has a variable region (VL), also called the variable light chain domain or light chain variable domain, followed by a constant light chain (CL) domain. The light chains of an antibody can be assigned to one of two types called kappa (κ) and lambda (λ) based on the amino acid sequence of their constant domains.

[0185] The "percent amino acid sequence identity (%)" to a reference polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in the reference polypeptide sequence when the sequences are aligned and any conservative substitutions for alignment are not considered as part of the sequence identity, if gaps are introduced as necessary to achieve the maximum percent sequence identity. Alignments for determining the percent amino acid sequence identity can be achieved in a variety of ways within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, Clustal W, Megalign (DNASTAR) software or the FASTA program package. One of ordinary skill in the art can determine appropriate parameters for alignment of sequences, including any algorithm necessary to achieve the maximum alignment over the full length of the sequences being compared. Alternatively, values for the identity rate can be generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was created by Genentech, Inc., the source code of which is filed in the user documentation of the U.S. Copyright Office (Washington D.C., 20559), registered under U.S. Copyright Registration No. TXU510087, and described in International Publication No. WO 2001 / 007611.

[0186] Unless otherwise indicated, for the purposes of this specification, the value of the percent amino acid sequence identity is generated using the ggsearch program of the FASTA package version 36.3.8c, or the subsequent BLOSUM50 comparison matrix. The FASTA program package is disclosed in Pearson and Lipman, Proc. Natl. Acad. Sci. USA 85:2444-2448 (1988); Pearson Meth. Enzymol. 266:227-258 (1996); and Pearson et al., Genomics 46:24-36 (1997), and is publicly available from www.fasta.bioch.virginia.edu / fasta_www2 / fasta_down.shtml or www.ebi.ac.uk / Tools / sss / fasta. Alternatively, the ggsearch (global protein:protein) program and default options (BLOSUM50; open: -10; ext: -2; Ktup = 2) can be used to compare sequences using a public server accessible at fasta.bioch.virginia.edu / fasta_www2 / index.cgi to ensure a global rather than local alignment is performed. The percent amino acid identity is indicated in the output alignment header.

[0187] An "isolated" antibody is one that has been separated from the components of its natural environment. In some embodiments, the antibody is purified until it has a purity of 95% or higher, 99% or higher as determined by, for example, electrophoretic (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatographic (e.g., ion exchange or reverse phase HPLC) methods. For a review of methods for assessing antibody purity, see, for example, Flatman et al., J. Chromatogr. B 848:79-87 (2007).

[0188] The term "nucleic acid molecule" or "polynucleotide" includes any compound and / or substance that comprises a polymer of nucleotides. Each nucleotide is composed of a base, specifically a purine base or a pyrimidine base (i.e., cytosine (C), guanine (G), adenine (A), thymine (T) or uracil (U)), a sugar (i.e., deoxyribose or ribose), and a phosphate group. Often, nucleic acid molecules are described by the sequence of bases, whereby the said bases represent the primary structure (linear structure) of the nucleic acid molecule. The sequence of bases is typically represented from 5' to 3'. In the present specification, the term nucleic acid molecule includes deoxyribonucleic acid (DNA), such as complementary DNA (cDNA) and genomic DNA, ribonucleic acid (RNA), in particular messenger RNA (mRNA), synthetic forms of DNA or RNA, and hybrid polymers comprising two or more of these molecules. The nucleic acid molecule may be linear or circular. In addition to this, the term nucleic acid molecule includes both sense and antisense strands, as well as both single-stranded and double-stranded forms. Furthermore, the nucleic acid molecules described herein may contain naturally occurring nucleotides or non-naturally occurring nucleotides. Examples of non-naturally occurring nucleotides include modified nucleotide bases having derivatized sugars or phosphate backbone linkages or chemically modified residues. Nucleic acid molecules also include, for example, DNA molecules and RNA molecules suitable as vectors for the direct expression of the antibodies of the present invention in vitro and / or in vivo in a host or patient. Such DNA (e.g., cDNA) or RNA (e.g., mRNA) vectors may or may not be modified. For example, mRNA can be chemically modified to improve the stability of the RNA vector and / or the expression of the encoded molecule, and the mRNA can be injected into a subject to enable the generation of antibodies in vivo (see, for example, Stadler et al., Nat. Med. 23(7):815-817, 2017, or EP2101823 B1).

[0189] "Isolated" nucleic acid refers to a nucleic acid molecule that has been separated from the components of its natural environment. Isolated nucleic acids include nucleic acid molecules normally present in cells that contain the nucleic acid molecule, but the nucleic acid molecule is present extrachromosomally or at a chromosomal location different from its natural chromosomal location.

[0190] "Isolated nucleic acid encoding an anti-STEAP1 antibody" refers to one or more nucleic acid molecules encoding the heavy and light chains (or fragments thereof) of an anti-STEAP1 antibody, including such one or more nucleic acid molecules within a single vector or separate vectors, and such one or more nucleic acid molecules are present at one or more locations within a host cell.

[0191] "Isolated nucleic acid encoding an anti-CD3 antibody" refers to one or more nucleic acid molecules encoding the heavy and light chains (or fragments thereof) of an anti-CD3 antibody, including such one or more nucleic acid molecules within a single vector or separate vectors, and such one or more nucleic acid molecules are present at one or more locations within a host cell.

[0192] As used herein, the term "vector" refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. This term includes not only vectors as self-replicating nucleic acid structures but also vectors integrated into the genome of a host cell into which the vector has been introduced. A particular vector can direct the expression of an operably linked nucleic acid. Such a vector is referred to herein as an "expression vector".

[0193] The terms "host cell", "host cell line" and "host cell culture" are used interchangeably and refer to a cell into which an exogenous nucleic acid has been introduced, including progeny of such a cell. Host cells include "transformants" and "transformed cells", and these cells include primary transformed cells and progeny derived therefrom, regardless of the number of passages. Progeny may not be completely identical to the parental cell in terms of nucleic acid content and may include mutations. Mutant progeny having the same function or biological activity as screened or selected in the original transformed cell are included herein.

[0194] The term "pharmaceutical preparation" refers to a preparation that is in a form in which the biological activity of the active ingredient contained in the preparation is effective and that does not contain additional components that are unacceptably toxic to the subject to which the preparation is administered.

[0195] "Pharmaceutically acceptable carrier" refers to a component in a pharmaceutical preparation other than the active ingredient that is non-toxic to the subject. Pharmaceutically acceptable carriers include, but are not limited to, buffers, excipients, stabilizers or preservatives.

[0196] As used herein, "administering" means a method of giving a dosage of a compound (e.g., an antigen-binding molecule of the invention or a nucleic acid encoding the antigen-binding molecule of the invention) or a composition (e.g., a pharmaceutical composition, e.g., a pharmaceutical composition comprising the antigen-binding molecule of the invention) to a subject. The compositions utilized in the methods described herein can be administered, for example, intramuscularly, intravenously, intradermally, transdermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrathoracically, intratracheally, intranasally, intravitreally, vaginally, rectally, topically, intratumorally, peritoneally, subcutaneously, subconjunctivally, intravesicularly, mucosally, pericardially, intraumbilically, intraocularly, orally, topically, locally, by inhalation, by injection, by infusion, by continuous infusion, directly by a target cell of a local perfusion bath, by catheter, by perfusion, in a cream, or in a lipid composition. The method of administration can vary depending on various factors (e.g., the compound or composition being administered and the severity of the condition, disease, or disorder being treated).

[0197] As used herein, "treatment" (and its grammatical variants, e.g., "treat" or "treating") refers to a clinical intervention in an attempt to alter the natural course of an individual being treated, which can be performed for prophylaxis or during the course of clinical pathology. Desirable effects of treatment include, but are not limited to, preventing the onset or recurrence of a disease, alleviating symptoms, reducing the direct or indirect pathological consequences of a disease, preventing metastasis, decreasing the rate of disease progression, improving or alleviating the condition, and remission or improvement of prognosis. In some embodiments, the antibodies of the invention are used to delay the onset of a disease or to delay the progression of a disease.

[0198] As used herein, "delaying the progression of" a disorder or disease means deferring, hindering, decelerating, retarding, stabilizing, and / or delaying the development of a disease or disorder (e.g., a cell proliferative disorder, such as cancer). This delay can be for various periods depending on the medical history and / or the individual being treated. As will be apparent to those skilled in the art, a sufficient or significant delay can in effect encompass prevention in that the individual does not develop the disease. For example, the development of advanced cancer such as the occurrence of metastasis can be delayed.

[0199] "Reducing" or "inhibiting" means, for example, the ability to produce an overall decrease of 20% or more, 50% or more, or 75%, 85%, 90%, 95% or more. In certain embodiments, reducing or inhibiting can refer to the effector function of an antigen-binding molecule mediated by the Fc region, and such effector functions specifically include complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cell phagocytosis (ADCP).

[0200] The terms "cancer" and "cancerous" refer to or describe physiological conditions in mammals typically characterized by uncontrolled cell growth. This definition includes both benign and malignant cancers. "Early cancer" or "early tumor" means a cancer that is neither invasive nor metastatic, or is classified as stage 0, 1, or 2 cancer. Examples of cancers include solid tumors such as brain cancer, breast cancer, colorectal cancer, endometrial cancer, kidney cancer, liver cancer, lung cancer, melanoma, pancreatic cancer, prostate cancer, stomach cancer, or thyroid cancer; and hematological malignancies such as Burkitt lymphoma (BL), multiple myeloma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), marginal zone lymphoma (MZL), small lymphocytic leukemia (SLL), lymphoplasmacytic lymphoma (LL), or Waldenström macroglobulinemia (WM), but are not limited to these.

[0201] As used herein, the term "tumor" refers to the growth and proliferation of all tumor cells, as well as all pre-cancerous and cancerous cells and tissues, whether malignant or benign. The terms "cancer", "cancerous", "cell proliferative disorder", "proliferative disorder", and "tumor" are not mutually exclusive as used herein.

[0202] The term "STEAP1-expressing cancer" refers to a cancer in which the cancer cells are characterized by overexpression of STEAP1 compared to the expression level of STEAP1 in equivalent non-cancerous cells. Examples of STEAP1-expressing cancers include, but are not limited to, breast cancer, bladder cancer, cervical cancer, colorectal cancer, Ewing sarcoma, lung cancer, ovarian cancer, and prostate cancer.

[0203] Prostate cancer is one of the most common cancers in men. Types of prostate cancer can include adenocarcinoma of the prostate, sarcoma of the prostate, transitional cell carcinoma of the prostate, small cell carcinoma of the prostate, neuroendocrine tumor of the prostate, and castration-resistant prostate cancer (CRPC). Prostate cancer can also be classified based on molecular signature. For example, prostate cancer can be classified into those with rearrangements in ETS family transcription factors (e.g., ERG, ETV1, ETV4, and FLI1) and those negative for ETS factors. ETS-positive prostate cancer may also include changes in PI3K and p53 signaling. ETS-negative prostate cancer may show recurrent mutations in SPOP, FOXA1, and IDH1; deletion of CHD1; and overexpression of SPINK1. In some cases, prostate cancer is metastatic prostate cancer (e.g., metastatic castration-resistant prostate cancer). In other examples, prostate cancer is recurrent or refractory prostate cancer.

[0204] Ewing sarcoma (also called Ewing's sarcoma or Ewing tumor) is a cancer of bone and soft tissue (e.g., cartilage or nerve). There are several types of Ewing sarcoma, including Ewing sarcoma of bone, extraskeletal Ewing sarcoma, peripheral primitive neuroectodermal tumor (pPNET), and Askin tumor. The cause of Ewing sarcoma is unknown. Symptoms include pain and swelling at the tumor site.

[0205] As used herein, the term "tumor antigen" can be understood as an antigen presented on the surface of tumor cells. These antigens may be presented on the cell surface together with an extracellular portion that is often bound to the transmembrane and cytoplasmic portions of the molecule. These antigens are presented only by tumor cells and can never be presented by normal cells. Tumor antigens may be expressed only on tumor cells or may represent tumor-specific mutations compared to normal cells. In this case, they are referred to as tumor-specific antigens. Tumor antigens presented by both tumor cells and normal cells are more common, and they are referred to as tumor-associated antigens. These tumor-associated antigens may be overexpressed compared to normal cells or may be accessible to antibodies that bind in tumor cells because the structure of tumor tissue is not small compared to normal tissue. Exemplary tumor antigens include, but are not limited to, prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), epithelial cell adhesion molecule (EpCAM), prostate-specific antigen (PSA), prostate acid phosphatase (PAP), STEAP2, and HBA-71. In some cases, TAAs for prostate cancer include prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), epithelial cell adhesion molecule (EpCAM), prostate-specific antigen (PSA), and prostate acid phosphatase (PAP). In some cases, TAAs for Ewing sarcoma include HBA-71, an antigen localized to the cell surface glycans of tumor cells.

[0206] The term "T cell receptor" or TCR refers to a receptor expressed on the surface of T cells. Exemplary T cell receptors include, but are not limited to, CD3.

[0207] An "effective amount" of a compound, e.g., a bispecific antigen-binding molecule of the invention or a composition thereof (e.g., a pharmaceutical composition), is present in at least a minimal amount necessary to achieve a desired therapeutic or prophylactic result, such as a measurable improvement or prevention of a particular disorder (e.g., a cell proliferative disorder, e.g., cancer). The effective amount herein can vary depending on factors such as the patient's disease state, age, gender, and weight, as well as the ability of the antibody to elicit a desired response in the individual. An effective amount is also one in which the therapeutically beneficial effect exceeds any toxic or detrimental effect of the treatment. In the case of prophylactic use, beneficial or desired results include elimination or reduction of the risk of a disease, reduction of the severity of a disease, or delay in the onset of a disease, including biochemical, histological, and / or behavioral symptoms of the disease, its complications, and intermediate pathological phenotypes that appear during the development of the disease. In the case of therapeutic use, beneficial or desired results include a decrease in one or more symptoms resulting from the disease, an improvement in the quality of life of a person suffering from the disease, a decrease in the dosage of other drugs required for treatment of the disease, enhancement of the effect of another drug (e.g., target-mediated), delay in the progression of the disease, and / or an extension of the survival period and other clinical outcomes. In the case of cancer or tumor, an effective amount of the drug reduces the number of cancer cells, reduces the tumor size, inhibits (i.e., delays to some extent or preferably stops) the invasion of cancer cells into peripheral organs, inhibits (i.e., delays to some extent or preferably stops) tumor metastasis, inhibits tumor growth to some extent, and / or reduces to some extent one or more of the symptoms associated with the disorder. The effective amount can be administered in a single dose or in multiple doses. In the present invention, the effective amount of a drug, compound, or pharmaceutical composition is an amount sufficient to directly or indirectly achieve a prophylactic or therapeutic treatment. As understood in the clinical art, the effective amount of a drug, compound, or pharmaceutical composition may or may not be achieved in combination with another drug, compound, or pharmaceutical composition. Thus, an "effective amount" can be considered in relation to the administration of one or more therapeutic agents, and a single agent can be considered to be administered in an effective amount if, alone or in combination with one or more other agents, a desired result can be achieved or is achieved.

[0208] As used herein, "first-line therapy" includes the primary treatment of a subject having cancer. In some cases, the cancer is a primary cancer. In other cases, the cancer is a metastatic or recurrent cancer. In some cases, first-line therapy includes chemotherapy. In other cases, the first-line treatment includes radiation therapy. One of ordinary skill in the art will readily appreciate that different first-line treatments may be applicable to different types of cancer.

[0209] In some cases, additional therapeutic agents include second-line therapy, third-line therapy, fourth-line therapy, or fifth-line therapy. As used herein, second-line therapy encompasses a treatment utilized after cessation of the primary or first-line treatment. Third-line therapy, fourth-line therapy, or fifth-line therapy encompasses subsequent treatments. As indicated by the naming convention, third-line therapy encompasses the course of treatment when the primary and second-line therapies have ceased.

[0210] As used herein, the terms "individual," "patient," or "subject" are used interchangeably and each refers to a mammal. Mammals include, but are not limited to, domestic animals (e.g., cows, sheep, cats, dogs, and horses), primates (e.g., humans and non-human primates such as monkeys), rabbits, and rodents (e.g., mice and rats). In certain embodiments, the individual, patient, or subject is a human.

[0211] II. Compositions In one aspect, the invention is based in part on an antigen-binding molecule (e.g., a monospecific and / or multispecific antigen-binding molecule). In certain embodiments, the antigen-binding molecule binds to STEAP1. In certain embodiments, the antigen-binding molecule is a multispecific antigen-binding molecule that binds to STEAP1 and one or more additional antigen(s) of interest. In certain embodiments, the multispecific antigen-binding molecule binds monovalently to STEAP1. The antigen-binding molecules of the invention are useful, for example, for the treatment or progression delay of cancer (e.g., STEAP1-expressing cancer).

[0212] Exemplary antigen-binding molecules that bind to STEAP1 An antigen-binding molecule that binds to STEAP1 In some embodiments, the present invention provides an isolated antigen-binding molecule that binds to STEAP1. In some embodiments, the antigen-binding molecule of the present invention comprises at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 CDRs shown in Table 1 (Kabat) or Table 2 (Chothia). In some cases, the antigen-binding molecule comprises a VH and / or VL shown in Table 1. [Table 1] [Table 2]

[0213] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises, consists essentially of, or consists of a CDR-H1, CDR-H2, and / or CDR-H3 of a VH sequence selected from SEQ ID NOs: 7, 17-25, 30-34, and 38, and / or a CDR-L1, CDR-L2, and / or CDR-L3 of a VL sequence selected from SEQ ID NOs: 8, 26-29, 39, and 69, an anti-STEAP1 heavy chain variable region (VH); and / or an anti-STEAP1 light chain variable region (VL) that comprises, consists essentially of, or consists of a CDR-L1, CDR-L2, and / or CDR-L3 of a VL sequence selected from SEQ ID NOs: 8, 26-29, 39, and 69. In some cases, at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 CDRs are selected from the CDRs of the VH sequences selected from SEQ ID NOs: 7, 17-25, 30-34, 38, and 68, and the VL sequences selected from SEQ ID NOs: 8, 26-29, 39, and 69. In some cases, the 6 CDRs are defined according to Kabat numbering (see Table 1). In other cases, the 6 CDRs are defined according to Chothia numbering (see Table 2). In further cases, the 6 CDRs are defined according to EU numbering.

[0214] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises a heavy-chain variable region (VH) against STEAP1 comprising CDR-H1, CDR-H2, and / or CDR-H3; and / or a light-chain variable region (VL) against STEAP1 comprising CDR-L1, CDR-L2, and / or CDR-L3; CDR-H1 is Xaa 1 Xaa 2 comprises YMA (SEQ ID NO: 35); wherein, Xaa 1 is Asp (D) or Asn (N); and Xaa 2 is His (H), Tyr (Y), or Phe (F); CDR-H2 comprises YIXaa 3 YDGXaa 4 Xaa 5 TXaa 6 comprises YGDSVKG (SEQ ID NO: 36); wherein, Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D), or Leu (L); Xaa 5 is Ser (S), Asp (D), or Asn (N); and Xaa 6 is Ser (S) or Tyr (Y); CDR-H3 comprises RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein, Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 contains the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 contains the amino acid sequence of SEQ ID NO: 6.

[0215] In some cases, the anti-STEAP1 antigen-binding molecule comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0216] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2 and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2 and / or CDR-L3; CDR-H1 contains the amino acid sequence of SEQ ID NO: 10, 1 or 9; CDR-H2 is YIXaa 3 YDGXaa 4 Xaa 5 TXaa 6 contains YGDSVKG (SEQ ID NO: 36); wherein Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D) or Leu (L); Xaa 5 is Ser (S), Asp (D) or Asn (N); and Xaa 6 is Ser (S) or Tyr (Y); CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 contains the amino acid sequence of SEQ ID NO: 4; CDR-L2 contains the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 contains the amino acid sequence of SEQ ID NO: 6.

[0217] In some cases, the anti-STEAP1 antigen-binding molecule comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0218] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2 and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2 and / or CDR-L3; wherein, CDR-H1 contains the amino acid sequence of SEQ ID NO: 10, 1 or 9; CDR-H2 contains the amino acid sequence of SEQ ID NO: 2, 11, 12 or 13; CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein, Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 contains the amino acid sequence of SEQ ID NO: 4; CDR-L2 contains the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 contains the amino acid sequence of SEQ ID NO: 6.

[0219] In some cases, the anti-STEAP1 antigen-binding molecule comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0220] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2 and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2 and / or CDR-L3; wherein, CDR-H1 is Xaa 1 Xaa 2 comprises YMA (SEQ ID NO: 35); wherein, Xaa 1 is Asp (D) or Asn (N); and Xaa 2 is His (H), Tyr (Y), or Phe (F); CDR-H2 comprises the amino acid sequence of SEQ ID NO: 2, 11, 12 or 13; CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 comprises (SEQ ID NO: 37); wherein, Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6.

[0221] In some cases, the anti-STEAP1 antigen-binding molecule comprises at least two, at least three, at least four, at least five, or all six of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0222] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2 and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2 and / or CDR-L3; wherein CDR-H1 is Xaa 1 Xaa 2 comprises YMA (SEQ ID NO: 35); wherein Xaa 1 is Asp (D) or Asn (N); and Xaa 2 is His (H), Tyr (Y), or Phe (F); CDR-H2 comprises the amino acid sequence of SEQ ID NO: 2, 11, 12 or 13; CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6.

[0223] In some cases, the anti-STEAP1 antigen-binding molecule comprises at least two, at least three, at least four, at least five, or all six of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0224] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises a heavy chain variable region (VH) against STEAP1 comprising CDR-H1, CDR-H2, and / or CDR-H3; and / or a light chain variable region (VL) against STEAP1 comprising CDR-L1, CDR-L2, and / or CDR-L3; wherein, CDR-H1 comprises Xaa 1 Xaa 2 YMA (SEQ ID NO: 35); wherein, Xaa 1 is Asp (D) or Asn (N); and Xaa 2 is His (H), Tyr (Y), or Phe (F); CDR-H2 comprises YIXaa 3 YDGXaa 4 Xaa 5 TXaa 6 YGDSVKG (SEQ ID NO: 36); wherein, Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D), or Leu (L); Xaa 5 is Ser (S), Asp (D), or Asn (N); and Xaa 6 is Ser (S) or Tyr (Y); CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6.

[0225] In some cases, the anti-STEAP1 antigen-binding molecule comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0226] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2 and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2 and / or CDR-L3; wherein CDR-H1 comprises the amino acid sequence of SEQ ID NO: 10, 1 or 9; CDR-H2 is YIXaa 3 YDGXaa 4 Xaa 5 TXaa 6 comprises YGDSVKG (SEQ ID NO: 36); wherein Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D) or Leu (L); Xaa 5 is Ser (S), Asp (D) or Asn (N); and Xaa 6 is Ser (S) or Tyr (Y); CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6.

[0227] In some cases, the anti-STEAP1 antigen-binding molecule comprises at least two, at least three, at least four, at least five, or all six of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0228] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2 and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2 and / or CDR-L3; CDR-H1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 10, 1 or 9; CDR-H2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 2, 11, 12, or 13; CDR-H3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 6. In some cases, the anti-STEAP1 antigen-binding molecule comprises at least two, at least three, at least four, at least five, or all six of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0229] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0230] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 11, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0231] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0232] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0233] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 13; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0234] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 16; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0235] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises a heavy-chain variable region (VH) against STEAP1 that includes CDR-H1, CDR-H2, and / or CDR-H3; and / or a light-chain variable region (VL) against STEAP1 that includes CDR-L1, CDR-L2, and / or CDR-L3; CDR-H1 comprises GFTFSXaa 10 Xaa 11 (SEQ ID NO: 63); wherein Xaa 10 is Asn (N) or Asp (D); and Xaa 11 is Tyr (Y), Phe (F), or His (H); CDR-H2 comprises Xaa 12 YDGXaa 13 Xaa 14 (SEQ ID NO: 64); wherein Xaa 12 is Asp (D) or Ser (S); Xaa 13 is Gly (G), Asp (D), or Leu (L); and Xaa 14 is Ser (S), Asp (D), or Asn (N); CDR-H3 comprises RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6.

[0236] In some cases, the anti-STEAP1 antigen-binding molecule comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0237] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2, and / or CDR-L3; CDR-H1 comprises the amino acid sequence of SEQ ID NO: 56, 58, or 59; CDR-H2 comprises 12 YDGXaa 13 Xaa 14 (SEQ ID NO: 64); wherein Xaa 12 is Asp (D) or Ser (S); Xaa 13 is Gly (G), Asp (D), or Leu (L); and Xaa 14 is Ser (S), Asp (D), or Asn (N); CDR-H3 comprises RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 contains the amino acid sequence of SEQ ID NO: 6.

[0238] In some cases, the anti-STEAP1 antigen-binding molecule comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0239] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2, and / or CDR-L3; CDR-H1 contains the amino acid sequence of SEQ ID NO: 56, 58, or 59; CDR-H2 contains the amino acid sequence of SEQ ID NO: 57, 60, 61, or 62; CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 contains the amino acid sequence of SEQ ID NO: 4; CDR-L2 contains the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 contains the amino acid sequence of SEQ ID NO: 6.

[0240] In some cases, the anti-STEAP1 antigen-binding molecule comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0241] In some embodiments, the antigen-binding molecule that binds to STEAP1 is an anti-STEAP1 heavy-chain variable region (VH) comprising CDR-H1, CDR-H2, and / or CDR-H3; and / or an anti-STEAP1 light-chain variable region (VL) comprising CDR-L1, CDR-L2, and / or CDR-L3; CDR-H1 comprises GFTFSXaa 10 Xaa 11 (SEQ ID NO: 63); wherein Xaa 10 is Asn (N) or Asp (D); and Xaa 11 is Tyr (Y), Phe (F), or His (H); CDR-H2 comprises the amino acid sequence of SEQ ID NO: 57, 60, 61, or 62; CDR-H3 comprises RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6.

[0242] In some cases, the anti-STEAP1 antigen-binding molecule comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0243] In some embodiments, the antigen-binding molecule that binds to STEAP1 is an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2, and / or CDR-L3; CDR-H1 comprises GFTFSXaa 10 Xaa 11 (SEQ ID NO: 63); wherein Xaa 10 is Asn (N) or Asp (D); and Xaa 11 is Tyr (Y), Phe (F), or His (H); CDR-H2 comprises the amino acid sequence of SEQ ID NO: 57, 60, 61, or 62; CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6.

[0244] In some cases, the anti-STEAP1 antigen-binding molecule comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0245] In some embodiments, the antigen-binding molecule that binds to STEAP1 is an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2, and / or CDR-L3; CDR-H1 comprises GFTFSXaa 10 Xaa 11 (SEQ ID NO: 63); wherein Xaa 10 is Asn (N) or Asp (D); and Xaa 11 is Tyr (Y), Phe (F) or His (H); CDR-H2 contains Xaa 12 YDGXaa 13 Xaa 14 (SEQ ID NO: 64); wherein Xaa 12 is Asp (D) or Ser (S); Xaa 13 is Gly (G), Asp (D) or Leu (L); and Xaa 14 is Ser (S), Asp (D) or Asn (N); CDR-H3 contains the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 contains the amino acid sequence of SEQ ID NO: 4; CDR-L2 contains the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 contains the amino acid sequence of SEQ ID NO: 6.

[0246] In some cases, the anti-STEAP1 antigen-binding molecule comprises all of at least 2, at least 3, at least 4, at least 5, or 6 CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0247] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2 and / or CDR-H3; and / or an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2 and / or CDR-L3; CDR-H1 contains the amino acid sequence of SEQ ID NO: 56, 58 or 59; CDR-H2 contains Xaa 12 YDGXaa 13 Xaa 14 (SEQ ID NO: 64); In the formula, Xaa 12 is Asp(D) or Ser(S); Xaa 13 is Gly(G), Asp(D) or Leu(L); and Xaa 14 is Ser(S), Asp(D) or Asn(N); CDR-H3 contains the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 contains the amino acid sequence of SEQ ID NO: 4; CDR-L2 contains the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 contains the amino acid sequence of SEQ ID NO: 6.

[0248] In some cases, the anti-STEAP1 antigen-binding molecule comprises at least two, at least three, at least four, at least five, or all six of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0249] In some embodiments, the antigen-binding molecule that binds to STEAP1 comprises a heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and / or CDR-H3; and / or a light chain variable region (VL) against STEAP1 comprising CDR-L1, CDR-L2, and / or CDR-L3; CDR-H1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 56, 58, or 59; CDR-H2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 57, 60, 61, or 62; CDR-H3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 6. In some cases, the anti-STEAP1 antigen-binding molecule comprises at least 2, at least 3, at least 4, at least 5, or all 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.

[0250] In some cases, the antigen-binding molecule comprises a CDR-H1 that comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 56; a CDR-H2 that comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 57; a CDR-H3 that comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 3; a CDR-L1 that comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 4; a CDR-L2 that comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 5; and a CDR-L3 that comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 6.

[0251] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 58, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 60, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0252] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 58, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 61, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0253] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 58, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 61, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0254] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of a CDR-H1 that comprises the amino acid sequence of SEQ ID NO: 59, a CDR-H2 that comprises the amino acid sequence of SEQ ID NO: 62, a CDR-H3 that comprises the amino acid sequence of SEQ ID NO: 15, a CDR-L1 that comprises the amino acid sequence of SEQ ID NO: 4, a CDR-L2 that comprises the amino acid sequence of SEQ ID NO: 5, and a CDR-L3 that comprises the amino acid sequence of SEQ ID NO: 6.

[0255] In some cases, the antigen-binding molecule comprises, consists essentially of, or consists of a CDR-H1 that comprises the amino acid sequence of SEQ ID NO: 59, a CDR-H2 that comprises the amino acid sequence of SEQ ID NO: 57, a CDR-H3 that comprises the amino acid sequence of SEQ ID NO: 16, a CDR-L1 that comprises the amino acid sequence of SEQ ID NO: 4, a CDR-L2 that comprises the amino acid sequence of SEQ ID NO: 5, and a CDR-L3 that comprises the amino acid sequence of SEQ ID NO: 6.

[0256] The antigen-binding molecule of the present invention can be a humanized antibody. In some cases, the antigen-binding molecule of the present invention comprises a constant region derived from an IgG framework region. In some cases, the IgG framework region is an IgG1, IgG2, or IgG4 framework region. In some cases, the IgG framework region is an IgG1 framework region.

[0257] In some embodiments, the antigen-binding molecule comprises a heavy-chain variable region comprising one or more (e.g., one, two, three, or all four) of framework region (FR)-H1 sequences having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 110; FR-H2 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 118; FR-H3 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 112; and / or FR-H4 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antigen-binding molecule comprises a heavy-chain variable region comprising FR-H2 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 118. In some embodiments, the antigen-binding molecule comprises a heavy-chain variable region comprising FR-H2 having the amino acid sequence of SEQ ID NO: 118. In other embodiments, the antigen-binding molecule comprises a heavy-chain variable region comprising FR-H2 having the amino acid sequence of SEQ ID NO: 120.

[0258] In some embodiments, the antigen-binding molecule comprises a heavy chain variable region comprising one or more (e.g., one, two, three, or all four) FR-H1 sequences having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 110; an FR-H2 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 111; an FR-H3 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 112; and / or an FR-H4 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 113.

[0259] In some embodiments, the antigen-binding molecule comprises a light chain variable region comprising one or more (e.g., one, two, three, or all four) of FR-L1 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 114; FR-L2 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 119; FR-L3 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 116; and / or FR-L4 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 117. In some embodiments, the antigen-binding molecule comprises a heavy chain variable region comprising FR-L2 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 119. In some embodiments, the antigen-binding molecule comprises a heavy chain variable region comprising FR-L2 having the amino acid sequence of SEQ ID NO: 119. In other embodiments, the antigen-binding molecule comprises a heavy chain variable region comprising FR-L2 having the amino acid sequence of SEQ ID NO: 121.

[0260] In some embodiments, the antigen-binding molecule comprises a light chain variable region comprising one or more (e.g., 1, 2, 3, or all 4) of FR-L1 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 114; FR-L2 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 115; FR-L3 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 116; and / or FR-L4 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 117.

[0261] For example, in some cases, the antigen-binding molecule comprises, consists essentially of, or consists of FR-H1 comprising the amino acid sequence of SEQ ID NO: 110; FR-H2 comprising the amino acid sequence of SEQ ID NO: 111; FR-H3 comprising the amino acid sequence of SEQ ID NO: 112; FR-H4 comprising the amino acid sequence of SEQ ID NO: 113; FR-L1 comprising the amino acid sequence of SEQ ID NO: 114; FR-L2 comprising the amino acid sequence of SEQ ID NO: 115; FR-L3 comprising the amino acid sequence of SEQ ID NO: 116; FR-L4 comprising the amino acid sequence of SEQ ID NO: 117.

[0262] In some embodiments, the antigen-binding molecule comprises a heavy-chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In some cases, the heavy-chain variable region comprises a VH sequence having at least 90% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In some cases, the heavy-chain variable region comprises a VH sequence having at least 95% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In some cases, the heavy-chain variable region comprises a VH sequence having at least 98% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In some cases, the heavy-chain variable region comprises a VH sequence having at least 99% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In some cases, the heavy-chain variable region comprises a VH sequence having 100% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In certain embodiments, a VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions as compared to SEQ ID NO: 7, 17-25, 30-34, 38, or 68, but an anti-STEAP1 antibody comprising such a sequence retains the ability to bind to STEAP1. In certain embodiments, 1 to 10 total amino acids are substituted, inserted and / or deleted in SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In certain embodiments, the substitutions, insertions, or deletions occur in regions outside of the CDRs (i.e., in the FRs).

[0263] In some embodiments, the antigen-binding molecule comprises a variable light chain region comprising a VL sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In some cases, the variable light chain region comprises a VL sequence having at least 90% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In some cases, the variable light chain region comprises a VL sequence having at least 95% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In some cases, the variable light chain region comprises a VL sequence having at least 98% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In some cases, the variable light chain region comprises a VL sequence having at least 99% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In some cases, the variable light chain region comprises a VL sequence having 100% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In certain embodiments, a VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions as compared to SEQ ID NO: 8, 26-29, 39 or 69, but an anti-STEAP1 antibody comprising such sequence retains the ability to bind to STEAP1. In certain embodiments, 1 to 10 total amino acids are substituted, inserted and / or deleted in SEQ ID NO: 8, 26-29, 39 or 69. In certain embodiments, the substitutions, insertions, or deletions occur in regions outside the CDRs (i.e., in the FRs).

[0264] In some embodiments, any antigen-binding molecule of the preceding embodiments is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 9, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 11, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 3. In some cases, the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 58, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 60, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 3. In some embodiments, the VH region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 30 (e.g., at least 95% sequence identity to SEQ ID NO: 30, at least 96% sequence identity to SEQ ID NO: 30, at least 97% sequence identity to SEQ ID NO: 30, at least 98% sequence identity to SEQ ID NO: 30, at least 99% sequence identity to SEQ ID NO: 30, or 100% sequence identity to SEQ ID NO: 30). In some embodiments, the VL region comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 27 (e.g., at least 95% sequence identity to SEQ ID NO: 27, at least 96% sequence identity to SEQ ID NO: 27, at least 97% sequence identity to SEQ ID NO: 27, at least 98% sequence identity to SEQ ID NO: 27, at least 99% sequence identity to SEQ ID NO: 27, or 100% sequence identity to SEQ ID NO: 27).

[0265] In some embodiments, any antigen-binding molecule of the preceding embodiments is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 9; (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 12; or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 3. In some cases, the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 58; (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 61; or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 3. In some embodiments, the VH region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 31 (e.g., at least 95% sequence identity to SEQ ID NO: 31, at least 96% sequence identity to SEQ ID NO: 31, at least 97% sequence identity to SEQ ID NO: 31, at least 98% sequence identity to SEQ ID NO: 31, at least 99% sequence identity to SEQ ID NO: 31, or 100% sequence identity to SEQ ID NO: 31). In some embodiments, the VL region comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4; (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5; or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 27 (e.g., at least 95% sequence identity to SEQ ID NO: 27, at least 96% sequence identity to SEQ ID NO: 27, at least 97% sequence identity to SEQ ID NO: 27, at least 98% sequence identity to SEQ ID NO: 27, at least 99% sequence identity to SEQ ID NO: 27, or 100% sequence identity to SEQ ID NO: 27).

[0266] In some embodiments, any antigen-binding molecule of the preceding embodiments is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 9, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 12, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 14. In some cases, the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 58, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 61, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 14. In some embodiments, the VH region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 32 (e.g., at least 95% sequence identity to SEQ ID NO: 32, at least 96% sequence identity to SEQ ID NO: 32, at least 97% sequence identity to SEQ ID NO: 32, at least 98% sequence identity to SEQ ID NO: 32, at least 99% sequence identity to SEQ ID NO: 32, or 100% sequence identity to SEQ ID NO: 32). In some embodiments, the VL region comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 27 (e.g., at least 95% sequence identity to SEQ ID NO: 27, at least 96% sequence identity to SEQ ID NO: 27, at least 97% sequence identity to SEQ ID NO: 27, at least 98% sequence identity to SEQ ID NO: 27, at least 99% sequence identity to SEQ ID NO: 27, or 100% sequence identity to SEQ ID NO: 27).

[0267] In some embodiments, any antigen-binding molecule of the preceding embodiments is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 10, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 13, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 15. In some cases, the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 59, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 62, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 15. In some embodiments, the VH region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 33 (e.g., at least 95% sequence identity to SEQ ID NO: 33, at least 96% sequence identity to SEQ ID NO: 33, at least 97% sequence identity to SEQ ID NO: 33, at least 98% sequence identity to SEQ ID NO: 33, at least 99% sequence identity to SEQ ID NO: 33, or 100% sequence identity to SEQ ID NO: 33). In some embodiments, the VL region comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 27 (e.g., at least 95% sequence identity to SEQ ID NO: 27, at least 96% sequence identity to SEQ ID NO: 27, at least 97% sequence identity to SEQ ID NO: 27, at least 98% sequence identity to SEQ ID NO: 27, at least 99% sequence identity to SEQ ID NO: 27, or 100% sequence identity to SEQ ID NO: 27).

[0268] In some embodiments, any antigen-binding molecule of the preceding embodiments is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 10, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 2, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 16. In some cases, the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 59, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 57, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 16. In some embodiments, the VH region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 34 (e.g., at least 95% sequence identity to SEQ ID NO: 34, at least 96% sequence identity to SEQ ID NO: 34, at least 97% sequence identity to SEQ ID NO: 34, at least 98% sequence identity to SEQ ID NO: 34, at least 99% sequence identity to SEQ ID NO: 34, or 100% sequence identity to SEQ ID NO: 34). In some embodiments, the VL region comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 27 (e.g., at least 95% sequence identity to SEQ ID NO: 27, at least 96% sequence identity to SEQ ID NO: 27, at least 97% sequence identity to SEQ ID NO: 27, at least 98% sequence identity to SEQ ID NO: 27, at least 99% sequence identity to SEQ ID NO: 27, or 100% sequence identity to SEQ ID NO: 27).

[0269] In some embodiments, the VH region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 68 (e.g., at least 95% sequence identity to SEQ ID NO: 68, at least 96% sequence identity to SEQ ID NO: 68, at least 97% sequence identity to SEQ ID NO: 68, at least 98% sequence identity to SEQ ID NO: 68, at least 99% sequence identity to SEQ ID NO: 68, or 100% sequence identity to SEQ ID NO: 68). In some embodiments, the VL region comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6. In some embodiments, the VL region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 69 (e.g., at least 95% sequence identity to SEQ ID NO: 69, at least 96% sequence identity to SEQ ID NO: 69, at least 97% sequence identity to SEQ ID NO: 69, at least 98% sequence identity to SEQ ID NO: 69, at least 99% sequence identity to SEQ ID NO: 69, or 100% sequence identity to SEQ ID NO: 69).

[0270] In some embodiments, any antigen-binding molecule of the preceding embodiments is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 35, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 36, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 37. In some cases, the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 63, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 64, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 37. In some embodiments, the VH region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 38 (e.g., at least 95% sequence identity to SEQ ID NO: 38, at least 96% sequence identity to SEQ ID NO: 38, at least 97% sequence identity to SEQ ID NO: 38, at least 98% sequence identity to SEQ ID NO: 38, at least 99% sequence identity to SEQ ID NO: 38, or 100% sequence identity to SEQ ID NO: 38). In some embodiments, the VL region comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 39 (e.g., at least 95% sequence identity to SEQ ID NO: 39, at least 96% sequence identity to SEQ ID NO: 39, at least 97% sequence identity to SEQ ID NO: 39, at least 98% sequence identity to SEQ ID NO: 39, at least 99% sequence identity to SEQ ID NO: 39, or 100% sequence identity to SEQ ID NO: 39).

[0271] In some embodiments, the antigen-binding molecule binds to an epitope on STEAP1 that comprises one or more amino acid residues selected from Ser101, His102, Gln103, and Lys281 of STEAP1. In some embodiments, the epitope comprises the amino acid residue Ser101 of ECL1 of STEAP1. In some embodiments, the epitope comprises the amino acid residue His102 of ECL1 of STEAP1. In some embodiments, the epitope comprises the amino acid residue Gln103 of ECL1 of STEAP1. In some embodiments, the epitope comprises the amino acid residue Lys281 of ECL3 of STEAP1. In some embodiments, the epitope comprises Ser101, His102, Gln103 of ECL1 of STEAP1, and Lys281 of ECL3 of STEAP1. In some embodiments, the epitope further comprises one or more additional amino acid residues selected from Trp195, Gln198, Gln201, Gln202, Asn203, and Lys204 of ECL2 of STEAP1. In some embodiments, the epitope does not comprise the amino acid residue Gln104 of STEAP1. In some embodiments, the epitope does not comprise the amino acid residue Tyr107 of STEAP1. In some embodiments, the epitope does not comprise the amino acid residue Asn194 of STEAP1. In some embodiments, the epitope does not comprise the amino acid residue Glu205 of STEAP1. In some embodiments, the epitope does not comprise the amino acid residue Ala207 of STEAP1.

[0272] In some embodiments, the antigen-binding molecule binds to human STEAP1 with a K as measured by a kinetic exclusion assay (KinExA®) of about 100 nM or less. D In some embodiments, the antigen-binding molecule binds to human STEAP1 with a K of from about 10 pM to about 100 nM. D In some embodiments, the antigen-binding molecule binds to human STEAP1 with a K of from about 100 pM to about 50 nM. D In some embodiments, the antigen-binding molecule binds to human STEAP1 with a K of from about 1 nM to about 30 nM. D In some embodiments, the antigen-binding molecule binds to cynomolgus STEAP1 with a K as measured by a kinetic exclusion assay (KinExA®) of about 100 nM or less. D In some embodiments, the antigen-binding molecule binds to cynomolgus STEAP1 with a K of from about 10 pM to about 100 nM. D In some embodiments, the antigen-binding molecule binds to cynomolgus STEAP1 with a K of from about 100 pM to about 50 nM. D In some embodiments, the antigen-binding molecule binds to cynomolgus STEAP1 with a K of from about 1 nM to about 30 nM. D In some embodiments, the antigen-binding molecule binds to cynomolgus STEAP1 with a K of from about 1 nM to about 30 nM.

[0273] Multispecific antigen-binding molecule In some embodiments, the present invention provides an isolated multispecific antigen-binding molecule comprising a first antigen-binding domain that binds to STEAP1 as described above. In some cases, the multispecific antigen-binding molecule binds monovalently to STEAP1. In some cases, the multispecific antigen-binding molecule further comprises a second binding domain that binds to a T cell receptor. In additional cases, the multispecific antigen-binding molecule comprises a third binding domain that binds to an additional antigen (e.g., a tumor-associated antigen).

[0274] In some embodiments, the multispecific antigen-binding molecule of the invention is a bispecific antigen-binding molecule (e.g., a bispecific antibody) comprising a first antigen-binding domain that binds to STEAP1 and a second antigen-binding domain that binds to a T cell receptor. Exemplary T cell receptors include cluster of differentiation 3 (CD3). In some cases, the second antigen-binding domain comprises an antibody or a fragment thereof that binds to CD3. Exemplary antigen-binding domains that bind to CD3 include, but are not limited to, 40G5c and 38E4v1.MD1. Additional antigen-binding domains that bind to CD3 (e.g., UCHT1.v9, 38E4v11, 30E4c, SP34v52, etc.) are described in U.S. Patent No. 10,174,124, International Publication No. 2015 / 095392, International Publication No. 2016 / 205520, and International Patent Application No. PCT / US2020 / 064635, each of which is incorporated herein by reference in its entirety.

[0275] In some embodiments, the second antigen-binding domain binds to an epitope on CD3 that includes the amino acid residue Glu6 of CD3. In some embodiments, the epitope further includes one or more additional amino acid residues selected from Gln1, Asp2, and Met7 of CD3. In some embodiments, the epitope includes the amino acid residues Gln1, Asp2, and Glu6 of CD3. In some embodiments, the epitope includes the amino acid residues Gln1, Asp2, Glu6, and Met7 of CD3. In some embodiments, the epitope does not include the amino acid residue Glu5 of CD3. In some embodiments, the epitope does not include the amino acid residues Gly3 and Glu5 of CD3. In some embodiments, the epitope consists of the amino acid residues Gln1, Asp2, Glu6, and Met7 of CD3. In some embodiments, the second antigen-binding domain can bind to a human CD3 polypeptide or a cyno CD3 polypeptide. In some embodiments, the human CD3 polypeptide or cyno CD3 polypeptide is a human CD3e polypeptide or a cyno CD3e polypeptide, respectively. In some embodiments, the human CD3 polypeptide or cyno CD3 polypeptide is a human CD3γ polypeptide or a cyno CD3γ polypeptide, respectively. In some embodiments, the second antigen-binding domain binds to the human CD3e polypeptide with a K D of about 100 nM or less. In some embodiments, the second antigen-binding domain binds to the human CD3e polypeptide with a K D of about 10 pM to about 100 nM. In some embodiments, the second antigen-binding domain binds to the human CD3e polypeptide with a K D of about 100 pM to about 50 nM. In some embodiments, the second antigen-binding domain binds to the human CD3e polypeptide with a K D of about 1 nM to about 10 nM.

[0276] In some embodiments, the second antigen-binding domain comprises at least one, at least two, at least three, at least four, at least five, or all six of the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of 38E4v1.MD1. In some cases, the second antigen-binding domain comprises at least one, at least two, at least three, at least four, at least five, or all six of the CDRs, wherein CDR-H1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 40, CDR-H2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 41, CDR-H3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 42, CDR-L1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 43, CDR-L2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 44, or CDR-L3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 45. In some cases, the second antigen-binding domain comprises a VH sequence having at least 80% (e.g., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 46. In some cases, the second antigen-binding domain comprises a VL sequence having at least 80% (e.g., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 47. In certain embodiments, a VH or VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions compared to SEQ ID NO: 46 or 47, but the multispecific antibody comprising such a sequence retains the ability to bind CD3. In certain embodiments, in SEQ ID NO: 46 or 47, a total of 1 to 10 amino acids have been substituted, inserted, and / or deleted. In certain embodiments, the substitutions, insertions, or deletions occur in regions outside of the CDRs (i.e., in the FRs).

[0277] In some embodiments, the second antigen-binding domain comprises at least one, at least two, at least three, at least four, at least five, or all six of the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of 40G5c. In some cases, the second antigen-binding domain comprises at least one, at least two, at least three, at least four, at least five, or all six of the CDRs, wherein CDR-H1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 48, CDR-H2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 49, CDR-H3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 50, CDR-L1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 51, CDR-L2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 52, or CDR-L3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 53. In some cases, the second antigen-binding domain comprises a VH sequence having at least 80% (e.g., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 54. In some cases, the second antigen-binding domain comprises a VL sequence having at least 80% (e.g., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 55. In certain embodiments, a VH or VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity contains substitutions (e.g., conservative substitutions), insertions, or deletions as compared to SEQ ID NO: 54 or 55, but the multispecific antibody comprising such a sequence retains the ability to bind to CD3. In certain embodiments, in SEQ ID NO: 54 or 55, a total of 1 to 10 amino acids have been substituted, inserted, and / or deleted. In certain embodiments, the substitutions, insertions, or deletions occur in regions outside of the CDRs (i.e., in the FRs).

[0278] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain that binds to STEAP1 and comprises a VH of an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and / or CDR-H3 selected from SEQ ID NOs: 7, 17-25, 30-34, 38, and 68; and / or a VL of an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2, and / or CDR-L3 selected from SEQ ID NOs: 8, 26-29, 39, and 69; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 CDRs are selected from the CDRs of the VH sequences selected from SEQ ID NOs: 7, 17-25, 30-34, 38, and 68, and the VL sequences selected from SEQ ID NOs: 8, 26-29, 39, and 69. In some cases, at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 CDRs are selected from the CDRs of 40G5c or 38E4v1.MD1. In some cases, the 6 CDRs are defined according to Kabat numbering. In other cases, the 6 CDRs are defined according to Chothia numbering. In further cases, the 6 CDRs are defined according to EU numbering.

[0279] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain that binds to STEAP1 and comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3; and an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3; wherein CDR-H1 comprises Xaa 1 Xaa 2 YMA (SEQ ID NO: 35); wherein Xaa 1 is Asp (D) or Asn (N); and Xaa 2is His (H), Tyr (Y), or Phe (F); CDR-H2 is YIXaa 3 YDGXaa 4 Xaa 5 TXaa 6 includes YGDSVKG (SEQ ID NO: 36); wherein, Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D), or Leu (L); Xaa 5 is Ser (S), Asp (D), or Asn (N); and Xaa 6 is Ser (S) or Tyr (Y); and CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37) includes; wherein, Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 includes the amino acid sequence of SEQ ID NO: 4; CDR-L2 includes the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 includes the amino acid sequence of SEQ ID NO: 6; and (B) It includes a second antigen-binding domain that binds to the T cell receptor. In some cases, the first antigen-binding domain includes all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain includes all of at least 1, at least 2, at least 3, at least 4, at least 5, or 6 of the CDRs of 40G5c or 38E4v1.MD1.

[0280] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain comprising a VH anti-STEAP1 heavy chain variable region that binds to STEAP1 and includes CDR-H1, CDR-H2, and CDR-H3; and a VL anti-STEAP1 light chain variable region that includes CDR-L1, CDR-L2, and CDR-L3; Here, CDR-H1 includes the amino acid sequence of SEQ ID NO: 10, 1, or 9; CDR-H2 is YIXaa 3 YDGXaa 4 Xaa 5 TXaa 6 and includes YGDSVKG (SEQ ID NO: 36); wherein Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D), or Leu (L); Xaa 5 is Ser (S), Asp (D), or Asn (N); and Xaa 6 is Ser (S) or Tyr (Y); CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 and includes (SEQ ID NO: 37); wherein Xaa 7is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 contains the amino acid sequence of SEQ ID NO: 4; CDR-L2 contains the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 contains the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain includes at least two, at least three, at least four, at least five, or all six of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain includes at least one, at least two, at least three, at least four, at least five, or all six CDRs of 40G5c or 38E4v1.MD1.

[0281] In some embodiments, the multispecific antigen-binding molecule comprises (A) a first antigen-binding domain comprising an anti-STEAP1 heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3; and an anti-STEAP1 light chain variable region (VL) that comprises CDR-L1, CDR-L2, and CDR-L3; wherein CDR-H1 contains the amino acid sequence of SEQ ID NO: 10, 1, or 9; CDR-H2 contains the amino acid sequence of SEQ ID NO: 2, 11, 12, or 13; CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa8 is Asn(N) or Asp(D); and Xaa 9 is Ala(A) or Gly(G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises at least two, at least three, at least four, at least five, or all six of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises at least one, at least two, at least three, at least four, at least five, or all six of the CDRs of 40G5c or 38E4v1.MD1.

[0282] In some embodiments, the multispecific antigen-binding molecule comprises (A) a first antigen-binding domain comprising a heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2 and CDR-H3; and a light chain variable region (VL) that binds to STEAP1 and comprises CDR-L1, CDR-L2 and CDR-L3; wherein CDR-H1 is Xaa 1 Xaa 2 comprises YMA (SEQ ID NO: 35); wherein Xaa 1 is Asp(D) or Asn(N); and Xaa 2 is His(H), Tyr(Y), or Phe(F); CDR-H2 comprises the amino acid sequence of SEQ ID NO: 2, 11, 12 or 13; CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa9 comprising (Sequence No. 37); wherein, Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of Sequence No. 4; CDR-L2 comprises the amino acid sequence of Sequence No. 5; and / or CDR-L3 comprises the amino acid sequence of Sequence No. 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises at least 2, at least 3, at least 4, at least 5, or all 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 of the CDRs of 40G5c or 38E4V1.MD1.

[0283] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain comprising an anti-STEAP1 heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3; and an anti-STEAP1 light chain variable region (VL) that comprises CDR-L1, CDR-L2, and CDR-L3; wherein, CDR-H1 comprises Xaa 1 Xaa 2 YMA (Sequence No. 35); wherein, Xaa 1 is Asp (D) or Asn (N); and Xaa 2 is His (H), Tyr (Y), or Phe (F); CDR-H2 comprises the amino acid sequence of SEQ ID NO: 2, 11, 12, or 13; CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises all of at least 1, at least 2, at least 3, at least 4, at least 5, or 6 of the CDRs of 40G5c or 38E4V1.MD1.

[0284] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain comprising an anti-STEAP1 heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3; and an anti-STEAP1 light chain variable region (VL) that comprises CDR-L1, CDR-L2, and CDR-L3; wherein CDR-H1 is Xaa 1 Xaa 2 comprises YMA (SEQ ID NO: 35); wherein Xaa 1 is Asp (D) or Asn (N); and Xaa 2 is His (H), Tyr (Y), or Phe (F); CDR-H2 is YIXaa 3 YDGXaa 4 Xaa 5 TXaa 6comprising YGDSVKG (SEQ ID NO: 36); wherein Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D) or Leu (L); Xaa 5 is Ser (S), Asp (D) or Asn (N); and Xaa 6 is Ser (S) or Tyr (Y); CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises all of at least 1, at least 2, at least 3, at least 4, at least 5, or 6 of the CDRs of 40G5c or 38E4V1.MD1.

[0285] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain comprising an anti-STEAP1 heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3; and an anti-STEAP1 light chain variable region (VL) that comprises CDR-L1, CDR-L2, and CDR-L3; where CDR-H1 comprises the amino acid sequence of SEQ ID NO: 10, 1, or 9; CDR-H2 is YIXaa 3 YDGXaa4 Xaa 5 TXaa 6 comprising YGDSVKG (SEQ ID NO: 36); wherein, Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D) or Leu (L); Xaa 5 is Ser (S), Asp (D) or Asn (N); and Xaa 6 is Ser (S) or Tyr (Y); CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises at least 2, at least 3, at least 4, at least 5, or all 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 of the CDRs of 40G5c or 38E4V1.MD1.

[0286] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain comprising a VH that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3; and a VL that binds to STEAP1 and comprises CDR-L1, CDR-L2, and CDR-L3 (CDR-H1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 10, 1, or 9; CDR-H2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 2, 11, 12, or 13; CDR-H3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 6); and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises at least 2, at least 3, at least 4, at least 5, or all 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 of the CDRs of 40G5c or 38E4V1.MD1.

[0287] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0288] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 11; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0289] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0290] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0291] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 13; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0292] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 16; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0293] In some embodiments, the multispecific antigen-binding molecule comprises a first antigen-binding domain that binds to STEAP1 and comprises: (A) a heavy chain variable region (VH) against STEAP1 comprising CDR-H1, CDR-H2, and CDR-H3; and a light chain variable region (VL) against STEAP1 comprising CDR-L1, CDR-L2, and CDR-L3; wherein CDR-H1 comprises GFTFSXaa 10 Xaa 11 (SEQ ID NO: 63); wherein Xaa 10 is Asn (N) or Asp (D); and Xaa 11 is Tyr (Y), Phe (F), or His (H); CDR-H2 comprises Xaa 12 YDGXaa 13 Xaa 14 (SEQ ID NO: 64); wherein Xaa 12 is Asp (D) or Ser (S); Xaa 13 is Gly (G), Asp (D), or Leu (L); and Xaa 14 is Ser (S), Asp (D), or Asn (N); CDR-H3 comprises RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises all of at least 1, at least 2, at least 3, at least 4, at least 5, or 6 of the CDRs of 40G5c or 38E4V1.MD1.

[0294] In some embodiments, the multispecific antigen-binding molecule comprises a first antigen-binding domain that (A) binds to STEAP1 and comprises a heavy chain variable region (VH) against STEAP1 comprising CDR-H1, CDR-H2 and CDR-H3; and a light chain variable region (VL) against STEAP1 comprising CDR-L1, CDR-L2 and CDR-L3; wherein CDR-H1 comprises the amino acid sequence of SEQ ID NO: 56, 58 or 59; CDR-H2 is Xaa 12 YDGXaa 13 Xaa 14 (SEQ ID NO: 64); wherein Xaa 12 is Asp (D) or Ser (S); Xaa 13 is Gly (G), Asp (D) or Leu (L); and Xaa 14 is Ser (S), Asp (D) or Asn (N); CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises at least two, at least three, at least four, at least five, or all six of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises at least one, at least two, at least three, at least four, at least five, or all six of the CDRs of 40G5c or 38E4V1.MD1.

[0295] In some embodiments, the multispecific antigen-binding molecule comprises (A) a first antigen-binding domain comprising an anti-STEAP1 heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2 and CDR-H3; and an anti-STEAP1 light chain variable region (VL) that comprises CDR-L1, CDR-L2 and CDR-L3; wherein CDR-H1 comprises the amino acid sequence of SEQ ID NO: 56, 58 or 59; CDR-H2 comprises the amino acid sequence of SEQ ID NO: 57, 60, 61 or 62; CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 comprises (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8is Asn(N) or Asp(D); and Xaa 9 is Ala(A) or Gly(G); CDR-L1 contains the amino acid sequence of SEQ ID NO: 4; CDR-L2 contains the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 contains the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain contains at least two, at least three, at least four, at least five, or all six of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain contains at least one, at least two, at least three, at least four, at least five, or all six of the CDRs of 40G5c or 38E4V1.MD1.

[0296] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain comprising a heavy chain variable region (VH) that binds to STEAP1 and contains CDR-H1, CDR-H2, and CDR-H3; and a light chain variable region (VL) that binds to STEAP1 and contains CDR-L1, CDR-L2, and CDR-L3; wherein CDR-H1 is GFTFSXaa 10 Xaa 11 (SEQ ID NO: 63); wherein Xaa 10 is Asn(N) or Asp(D); and Xaa 11 is Tyr(Y), Phe(F), or His(H); CDR-H2 contains the amino acid sequence of SEQ ID NO: 57, 60, 61, or 62; CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa9 comprising (SEQ ID NO: 37); wherein, Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises at least 2, at least 3, at least 4, at least 5, or all 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 of the CDRs of 40G5c or 38E4V1.MD1.

[0297] In some embodiments, the multispecific antigen-binding molecule comprises (A) a first antigen-binding domain comprising an anti-STEAP1 heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3; and an anti-STEAP1 light chain variable region (VL) that comprises CDR-L1, CDR-L2, and CDR-L3; wherein, CDR-H1 is GFTFSXaa 10 Xaa 11 comprising (SEQ ID NO: 63); wherein, Xaa 10 is Asn (N) or Asp (D); and Xaa 11 is Tyr (Y), Phe (F), or His (H); CDR-H2 comprises the amino acid sequence of SEQ ID NO: 57, 60, 61, or 62; CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises at least 2, at least 3, at least 4, at least 5, or all 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 of the CDRs of 40G5c or 38E4V1.MD1.

[0298] In some embodiments, the multispecific antigen-binding molecule comprises (A) a first antigen-binding domain comprising an anti-STEAP1 heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3; and an anti-STEAP1 light chain variable region (VL) that comprises CDR-L1, CDR-L2, and CDR-L3; wherein CDR-H1 is GFTFSXaa 10 Xaa 11 (SEQ ID NO: 63); wherein Xaa 10 is Asn (N) or Asp (D); and Xaa 11 is Tyr (Y), Phe (F), or His (H); CDR-H2 is Xaa 12 YDGXaa 13 Xaa 14 (SEQ ID NO: 64); wherein Xaa 12 is Asp (D) or Ser (S); Xaa 13 is Gly (G), Asp (D) or Leu (L); and Xaa 14 is Ser (S), Asp (D) or Asn (N); CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises all of at least 2, at least 3, at least 4, at least 5, or 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises all of at least 1, at least 2, at least 3, at least 4, at least 5, or 6 of the CDRs of 40G5c or 38E4V1.MD1.

[0299] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain comprising an anti-STEAP1 heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2 and CDR-H3; and an anti-STEAP1 light chain variable region (VL) that comprises CDR-L1, CDR-L2 and CDR-L3; wherein CDR-H1 comprises the amino acid sequence of SEQ ID NO: 56, 58 or 59; CDR-H2 is Xaa 12 YDGXaa 13 Xaa 14 (SEQ ID NO: 64); wherein Xaa 12is Asp(D) or Ser(S); Xaa 13 is Gly(G), Asp(D) or Leu(L); and Xaa 14 is Ser(S), Asp(D) or Asn(N); CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises at least 2, at least 3, at least 4, at least 5, or all 6 of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 of the CDRs of 40G5c or 38E4V1.MD1.

[0300] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain comprising a VH that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3; and a VL that binds to STEAP1 and comprises CDR-L1, CDR-L2, and CDR-L3 (CDR-H1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 56, 58, or 59; CDR-H2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 57, 60, 61, or 62; CDR-H3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15; CDR-L1 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 6); and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the first antigen-binding domain comprises at least two, at least three, at least four, at least five, or all six of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises at least one, at least two, at least three, at least four, at least five, or all six of the CDRs of 40G5c or 38E4V1.MD1.

[0301] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 56, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 57, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0302] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 58, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 60, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0303] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 58, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 61, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0304] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 58, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 61, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0305] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 59, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 62, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0306] In some cases, the first antigen-binding domain comprises, consists essentially of, or consists of CDR-H1 comprising the amino acid sequence of SEQ ID NO: 59; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 57; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 16; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0307] The multispecific antigen-binding molecule of the invention can be a humanized antibody. In some cases, the first antigen-binding domain and / or the second antigen-binding domain each independently comprises a constant region derived from an IgG framework region. In some cases, the IgG framework region is an IgG1, IgG2 or IgG4 framework region. In some cases, the IgG framework region is an IgG1 framework region.

[0308] In some embodiments, the multispecific antigen-binding molecule comprises a first antigen-binding domain comprising a heavy-chain variable region comprising one or more (e.g., one, two, three, or all four) FR-H1 sequences having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 110; an FR-H2 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 111; an FR-H3 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 112; and / or an FR-H4 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 113.

[0309] In some embodiments, the multispecific antigen-binding molecule comprises a first antigen-binding domain comprising a light-chain variable region comprising one or more (e.g., one, two, three, or all four) FR-L1 sequences having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 114; an FR-L2 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 115; an FR-L3 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 116; and / or an FR-L4 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 117.

[0310] For example, in some embodiments, the multispecific antigen-binding molecule comprises a first antigen-binding domain comprising: (A) FR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 110; FR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 111; FR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 112; FR-H4 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 113; FR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 114; FR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 115; FR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 116; and FR-L4 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 117.

[0311] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain comprising a VH sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the VH sequence of the first antigen-binding domain comprises at least 90% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In some cases, the VH sequence of the first antigen-binding domain comprises at least 95% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In some cases, the VH sequence of the first antigen-binding domain comprises at least 98% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In some cases, the VH sequence of the first antigen-binding domain comprises at least 99% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In some cases, the VH sequence of the first antigen-binding domain comprises 100% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises a VH sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 46 or 54. In some cases, the VH sequence of the second antigen-binding domain comprises at least 95% sequence identity to SEQ ID NO: 46 or 54. In some cases, the VH sequence of the second antigen-binding domain comprises at least 99% sequence identity to SEQ ID NO: 46 or 54. In some cases, the VH sequence of the second antigen-binding domain comprises 100% sequence identity to SEQ ID NO: 46 or 54.

[0312] In some embodiments, the multispecific antigen-binding molecule comprises: (A) a first antigen-binding domain comprising a VL sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69; and (B) a second antigen-binding domain that binds to a T cell receptor. In some cases, the VL sequence comprises at least 90% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In some cases, the VL sequence comprises at least 95% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In some cases, the VL sequence comprises at least 98% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In some cases, the VL sequence comprises at least 99% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In some cases, the VL sequence comprises 100% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69. In some cases, the second antigen-binding domain binds to CD3. In some cases, the second antigen-binding domain comprises a VL sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 47 or 55. In some cases, the VL sequence of the second antigen-binding domain comprises at least 95% sequence identity to SEQ ID NO: 47 or 55. In some cases, the VL sequence of the second antigen-binding domain comprises at least 99% sequence identity to SEQ ID NO: 47 or 55. In some cases, the VL sequence of the second antigen-binding domain comprises 100% sequence identity to SEQ ID NO: 47 or 55.

[0313] In some embodiments, the multispecific antigen-binding molecule of the invention binds to STEAP1 and comprises a first antigen-binding domain comprising at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 CDRs shown in Table 1 or Table 2. In some cases, the first antigen-binding domain comprises a VH and / or a VL shown in Table 1. In some cases, the multispecific antigen-binding molecule comprises a second antigen-binding domain that binds to a T cell receptor (e.g., CD3). In some cases, the second antigen-binding domain that binds to CD3 comprises at least 1, at least 2, at least 3, at least 4, at least 5, or all 6 CDRs shown in Table 1 or Table 2. In some cases, the second antigen-binding domain that binds to CD3 comprises a VH and / or a VL shown in Table 1.

[0314] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a first antigen-binding domain that binds to STEAP1 and a second antigen-binding domain that binds to a T cell receptor (e.g., CD3). In some embodiments, the first antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 9; (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 11; or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 3. In some cases, the VH region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 58; (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 60; or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 3. In some embodiments, the VH region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 30 (e.g., at least 95% sequence identity to SEQ ID NO: 30, at least 96% sequence identity to SEQ ID NO: 30, at least 97% sequence identity to SEQ ID NO: 30, at least 98% sequence identity to SEQ ID NO: 30, at least 99% sequence identity to SEQ ID NO: 30, or 100% sequence identity to SEQ ID NO: 30). In some embodiments, the VL region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4; (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5; or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 27 (e.g., at least 95% sequence identity to SEQ ID NO: 27, at least 96% sequence identity to SEQ ID NO: 27, at least 97% sequence identity to SEQ ID NO: 27, at least 98% sequence identity to SEQ ID NO: 27, at least 99% sequence identity to SEQ ID NO: 27, or 100% sequence identity to SEQ ID NO: 27). In some cases, the second antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 40 or 48, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 41 or 49, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 42 or 50. In some embodiments, the VH region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 46 or 54 (e.g., at least 95% sequence identity to SEQ ID NO: 46 or 54, at least 96% sequence identity to SEQ ID NO: 46 or 54, at least 97% sequence identity to SEQ ID NO: 46 or 54, at least 98% sequence identity to SEQ ID NO: 46 or 54, at least 99% sequence identity to SEQ ID NO: 46 or 54, or 100% sequence identity to SEQ ID NO: 46 or 54). In some embodiments, the VL region of the second antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 43 or 51, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 44 or 52, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 45 or 53.In some embodiments, the VL region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 47 or 55 (e.g., at least 95% sequence identity to SEQ ID NO: 47 or 55, at least 96% sequence identity to SEQ ID NO: 47 or 55, at least 97% sequence identity to SEQ ID NO: 47 or 55, at least 98% sequence identity to SEQ ID NO: 47 or 55, at least 99% sequence identity to SEQ ID NO: 47 or 55, or 100% sequence identity to SEQ ID NO: 47 or 55).

[0315] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a first antigen-binding domain that binds to STEAP1 and a second antigen-binding domain that binds to a T cell receptor (e.g., CD3). In some embodiments, the first antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) a CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 9; (b) a CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 12; or (c) a CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 3. In some cases, the VH region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) a CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 58; (b) a CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 61; or (c) a CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 3. In some embodiments, the VH region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 31 (e.g., at least 95% sequence identity to SEQ ID NO: 31, at least 96% sequence identity to SEQ ID NO: 31, at least 97% sequence identity to SEQ ID NO: 31, at least 98% sequence identity to SEQ ID NO: 31, at least 99% sequence identity to SEQ ID NO: 31, or 100% sequence identity to SEQ ID NO: 31). In some embodiments, the VL region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) a CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4; (b) a CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5; or (c) a CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 27 (e.g., at least 95% sequence identity to SEQ ID NO: 27, at least 96% sequence identity to SEQ ID NO: 27, at least 97% sequence identity to SEQ ID NO: 27, at least 98% sequence identity to SEQ ID NO: 27, at least 99% sequence identity to SEQ ID NO: 27, or 100% sequence identity to SEQ ID NO: 27). In some cases, the second antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 40 or 48, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 41 or 49, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 42 or 50. In some embodiments, the VH region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 46 or 54 (e.g., at least 95% sequence identity to SEQ ID NO: 46 or 54, at least 96% sequence identity to SEQ ID NO: 46 or 54, at least 97% sequence identity to SEQ ID NO: 46 or 54, at least 98% sequence identity to SEQ ID NO: 46 or 54, at least 99% sequence identity to SEQ ID NO: 46 or 54, or 100% sequence identity to SEQ ID NO: 46 or 54). In some embodiments, the VL region of the second antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 43 or 51, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 44 or 52, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 45 or 53.In some embodiments, the VL region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 47 or 55 (e.g., at least 95% sequence identity to SEQ ID NO: 47 or 55, at least 96% sequence identity to SEQ ID NO: 47 or 55, at least 97% sequence identity to SEQ ID NO: 47 or 55, at least 98% sequence identity to SEQ ID NO: 47 or 55, at least 99% sequence identity to SEQ ID NO: 47 or 55, or 100% sequence identity to SEQ ID NO: 47 or 55).

[0316] In some embodiments, any of the multispecific antigen-binding molecules of the preceding embodiments comprises a first antigen-binding domain that binds to STEAP1 and a second antigen-binding domain that binds to a T cell receptor (e.g., CD3). In some embodiments, the first antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 9, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 12, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 14. In some cases, the VH region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 58, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 61, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 14. In some embodiments, the VH region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 32 (e.g., at least 95% sequence identity to SEQ ID NO: 32, at least 96% sequence identity to SEQ ID NO: 32, at least 97% sequence identity to SEQ ID NO: 32, at least 98% sequence identity to SEQ ID NO: 32, at least 99% sequence identity to SEQ ID NO: 32, or 100% sequence identity to SEQ ID NO: 32). In some embodiments, the VL region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 27 (e.g., at least 95% sequence identity to SEQ ID NO: 27, at least 96% sequence identity to SEQ ID NO: 27, at least 97% sequence identity to SEQ ID NO: 27, at least 98% sequence identity to SEQ ID NO: 27, at least 99% sequence identity to SEQ ID NO: 27, or 100% sequence identity to SEQ ID NO: 27). In some cases, the second antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 40 or 48, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 41 or 49, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 42 or 50. In some embodiments, the VH region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 46 or 54 (e.g., at least 95% sequence identity to SEQ ID NO: 46 or 54, at least 96% sequence identity to SEQ ID NO: 46 or 54, at least 97% sequence identity to SEQ ID NO: 46 or 54, at least 98% sequence identity to SEQ ID NO: 46 or 54, at least 99% sequence identity to SEQ ID NO: 46 or 54, or 100% sequence identity to SEQ ID NO: 46 or 54). In some embodiments, the VL region of the second antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 43 or 51, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 44 or 52, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 45 or 53.In some embodiments, the VL region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 47 or 55 (e.g., at least 95% sequence identity to SEQ ID NO: 47 or 55, at least 96% sequence identity to SEQ ID NO: 47 or 55, at least 97% sequence identity to SEQ ID NO: 47 or 55, at least 98% sequence identity to SEQ ID NO: 47 or 55, at least 99% sequence identity to SEQ ID NO: 47 or 55, or 100% sequence identity to SEQ ID NO: 47 or 55).

[0317] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a first antigen-binding domain that binds to STEAP1 and a second antigen-binding domain that binds to a T cell receptor (e.g., CD3). In some embodiments, the first antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) a CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 10, (b) a CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 13, or (c) a CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 15. In some cases, the VH region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) a CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 59, (b) a CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 62, or (c) a CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 15. In some embodiments, the VH region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 33 (e.g., at least 95% sequence identity to SEQ ID NO: 33, at least 96% sequence identity to SEQ ID NO: 33, at least 97% sequence identity to SEQ ID NO: 33, at least 98% sequence identity to SEQ ID NO: 33, at least 99% sequence identity to SEQ ID NO: 33, or 100% sequence identity to SEQ ID NO: 33). In some embodiments, the VL region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) a CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4, (b) a CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5, or (c) a CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 27 (e.g., at least 95% sequence identity to SEQ ID NO: 27, at least 96% sequence identity to SEQ ID NO: 27, at least 97% sequence identity to SEQ ID NO: 27, at least 98% sequence identity to SEQ ID NO: 27, at least 99% sequence identity to SEQ ID NO: 27, or 100% sequence identity to SEQ ID NO: 27). In some cases, the second antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 40 or 48, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 41 or 49, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 42 or 50. In some embodiments, the VH region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 46 or 54 (e.g., at least 95% sequence identity to SEQ ID NO: 46 or 54, at least 96% sequence identity to SEQ ID NO: 46 or 54, at least 97% sequence identity to SEQ ID NO: 46 or 54, at least 98% sequence identity to SEQ ID NO: 46 or 54, at least 99% sequence identity to SEQ ID NO: 46 or 54, or 100% sequence identity to SEQ ID NO: 46 or 54). In some embodiments, the VL region of the second antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 43 or 51, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 44 or 52, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 45 or 53.In some embodiments, the VL region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 47 or 55 (e.g., at least 95% sequence identity to SEQ ID NO: 47 or 55, at least 96% sequence identity to SEQ ID NO: 47 or 55, at least 97% sequence identity to SEQ ID NO: 47 or 55, at least 98% sequence identity to SEQ ID NO: 47 or 55, at least 99% sequence identity to SEQ ID NO: 47 or 55, or 100% sequence identity to SEQ ID NO: 47 or 55).

[0318] In some embodiments, any of the multispecific antigen-binding molecules of the preceding embodiments comprises a first antigen-binding domain that binds to STEAP1 and a second antigen-binding domain that binds to a T cell receptor (e.g., CD3). In some embodiments, the first antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 10, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 2, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 16. In some cases, the VH region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 59, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 57, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 16. In some embodiments, the VH region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 34 (e.g., at least 95% sequence identity to SEQ ID NO: 34, at least 96% sequence identity to SEQ ID NO: 34, at least 97% sequence identity to SEQ ID NO: 34, at least 98% sequence identity to SEQ ID NO: 34, at least 99% sequence identity to SEQ ID NO: 34, or 100% sequence identity to SEQ ID NO: 34). In some embodiments, the VL region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 27 (e.g., at least 95% sequence identity to SEQ ID NO: 27, at least 96% sequence identity to SEQ ID NO: 27, at least 97% sequence identity to SEQ ID NO: 27, at least 98% sequence identity to SEQ ID NO: 27, at least 99% sequence identity to SEQ ID NO: 27, or 100% sequence identity to SEQ ID NO: 27). In some cases, the second antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 40 or 48, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 41 or 49, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 42 or 50. In some embodiments, the VH region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 46 or 54 (e.g., at least 95% sequence identity to SEQ ID NO: 46 or 54, at least 96% sequence identity to SEQ ID NO: 46 or 54, at least 97% sequence identity to SEQ ID NO: 46 or 54, at least 98% sequence identity to SEQ ID NO: 46 or 54, at least 99% sequence identity to SEQ ID NO: 46 or 54, or 100% sequence identity to SEQ ID NO: 46 or 54). In some embodiments, the VL region of the second antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 43 or 51, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 44 or 52, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 45 or 53).In some embodiments, the VL region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 47 or 55 (e.g., at least 95% sequence identity to SEQ ID NO: 47 or 55, at least 96% sequence identity to SEQ ID NO: 47 or 55, at least 97% sequence identity to SEQ ID NO: 47 or 55, at least 98% sequence identity to SEQ ID NO: 47 or 55, at least 99% sequence identity to SEQ ID NO: 47 or 55, or 100% sequence identity to SEQ ID NO: 47 or 55).

[0319] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a first antigen-binding domain that binds to STEAP1 and a second antigen-binding domain that binds to a T cell receptor (e.g., CD3). In some embodiments, the first antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 35, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 36, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 37. In some cases, the VH region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 63, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 64, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 37. In some embodiments, the VH region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 38 (e.g., at least 95% sequence identity to SEQ ID NO: 38, at least 96% sequence identity to SEQ ID NO: 38, at least 97% sequence identity to SEQ ID NO: 38, at least 98% sequence identity to SEQ ID NO: 38, at least 99% sequence identity to SEQ ID NO: 38, or 100% sequence identity to SEQ ID NO: 38). In some embodiments, the VL region of the first antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 4, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 5, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 6.In some embodiments, the VL region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 39 (e.g., at least 95% sequence identity to SEQ ID NO: 39, at least 96% sequence identity to SEQ ID NO: 39, at least 97% sequence identity to SEQ ID NO: 39, at least 98% sequence identity to SEQ ID NO: 39, at least 99% sequence identity to SEQ ID NO: 39, or 100% sequence identity to SEQ ID NO: 39). In some cases, the second antigen-binding domain is characterized by a VH region and a VL region, and the VH region comprises one, two, or all three of the following CDRs: (a) CDR-H1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 40 or 48, (b) CDR-H2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 41 or 49, or (c) CDR-H3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 42 or 50. In some embodiments, the VH region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 46 or 54 (e.g., at least 95% sequence identity to SEQ ID NO: 46 or 54, at least 96% sequence identity to SEQ ID NO: 46 or 54, at least 97% sequence identity to SEQ ID NO: 46 or 54, at least 98% sequence identity to SEQ ID NO: 46 or 54, at least 99% sequence identity to SEQ ID NO: 46 or 54, or 100% sequence identity to SEQ ID NO: 46 or 54). In some embodiments, the VL region of the second antigen-binding domain comprises one, two, or all three of the following CDRs: (a) CDR-L1 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 43 or 51, (b) CDR-L2 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 44 or 52, or (c) CDR-L3 comprising, consisting essentially of, or consisting of the amino acid sequence of SEQ ID NO: 45 or 53.In some embodiments, the VL region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 47 or 55 (e.g., at least 95% sequence identity to SEQ ID NO: 47 or 55, at least 96% sequence identity to SEQ ID NO: 47 or 55, at least 97% sequence identity to SEQ ID NO: 47 or 55, at least 98% sequence identity to SEQ ID NO: 47 or 55, at least 99% sequence identity to SEQ ID NO: 47 or 55, or 100% sequence identity to SEQ ID NO: 47 or 55).

[0320] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a first antigen-binding domain that binds to STEAP1 and a second antigen-binding domain that binds to a T cell receptor (e.g., CD3). In some embodiments, the VH region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 68 (e.g., at least 95% sequence identity to SEQ ID NO: 68, at least 96% sequence identity to SEQ ID NO: 68, at least 97% sequence identity to SEQ ID NO: 68, at least 98% sequence identity to SEQ ID NO: 68, at least 99% sequence identity to SEQ ID NO: 68, or 100% sequence identity to SEQ ID NO: 68). In some embodiments, the VL region of the first antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 69 (e.g., at least 95% sequence identity to SEQ ID NO: 69, at least 96% sequence identity to SEQ ID NO: 69, at least 97% sequence identity to SEQ ID NO: 69, at least 98% sequence identity to SEQ ID NO: 69, at least 99% sequence identity to SEQ ID NO: 69, or 100% sequence identity to SEQ ID NO: 69). In some embodiments, the VH region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 46 or 54 (e.g., at least 95% sequence identity to SEQ ID NO: 46 or 54, at least 96% sequence identity to SEQ ID NO: 46 or 54, at least 97% sequence identity to SEQ ID NO: 46 or 54, at least 98% sequence identity to SEQ ID NO: 46 or 54, at least 99% sequence identity to SEQ ID NO: 46 or 54, or 100% sequence identity to SEQ ID NO: 46 or 54).In some embodiments, the VL region of the second antigen-binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 47 or 55 (e.g., at least 95% sequence identity to SEQ ID NO: 47 or 55, at least 96% sequence identity to SEQ ID NO: 47 or 55, at least 97% sequence identity to SEQ ID NO: 47 or 55, at least 98% sequence identity to SEQ ID NO: 47 or 55, at least 99% sequence identity to SEQ ID NO: 47 or 55, or 100% sequence identity to SEQ ID NO: 47 or 55).

[0321] In some embodiments, any multispecific antigen-binding molecule of any of the preceding embodiments comprises an anti-STEAP1 heavy chain constant region having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 83, and an anti-STEAP1 light chain constant region having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 82.

[0322] In some embodiments, any multispecific antigen-binding molecule of any of the preceding embodiments comprises an anti-STEAP1 heavy chain constant region having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 85, and an anti-STEAP1 light chain constant region having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 84.

[0323] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a heavy chain constant region of anti-CD3 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 83, and a light chain constant region of anti-CD3 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 82.

[0324] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a heavy chain constant region of anti-CD3 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 85, and a light chain constant region of anti-CD3 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 84.

[0325] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a heavy chain of anti-STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 71, and a light chain of anti-STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 70.

[0326] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a heavy chain against STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 73, and a light chain against STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 72.

[0327] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a heavy chain against STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 75, and a light chain against STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 74.

[0328] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a heavy chain against STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 77, and a light chain against STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 76.

[0329] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a heavy chain constant region of an anti-STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 122, and a light chain constant region of an anti-STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 123.

[0330] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a heavy chain constant region of an anti-STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 126, and a light chain constant region of an anti-STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 127.

[0331] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a heavy chain constant region of anti-STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 130, and a light chain constant region of anti-STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 131.

[0332] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises a heavy chain constant region of anti-STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 134, and a light chain constant region of anti-STEAP1 having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 135.

[0333] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises an anti-STEAP1 heavy chain constant region having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 138, and an anti-STEAP1 light chain constant region having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 139.

[0334] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises an anti-STEAP1 heavy chain constant region having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 142, and an anti-STEAP1 light chain constant region having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 143.

[0335] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises an anti-CD3 heavy chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 79, and an anti-CD3 light chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 78.

[0336] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises an anti-CD3 heavy chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 81, and an anti-CD3 light chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 80.

[0337] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises an anti-CD3 heavy chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 124, and an anti-CD3 light chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 125.

[0338] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises an anti-CD3 heavy chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 128, and an anti-CD3 light chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 129.

[0339] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises an anti-CD3 heavy chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 132, and an anti-CD3 light chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 133.

[0340] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises an anti-CD3 heavy chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 136, and an anti-CD3 light chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 137.

[0341] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises an anti-CD3 heavy chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 140, and an anti-CD3 light chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 141.

[0342] In some embodiments, any multispecific antigen-binding molecule of the preceding embodiments comprises an anti-CD3 heavy chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 144, and an anti-CD3 light chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 145.

[0343] In some embodiments, the multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 122, an anti-STEAP1 light chain comprising SEQ ID NO: 123, an anti-CD3 heavy chain comprising SEQ ID NO: 124, and an anti-CD3 light chain comprising SEQ ID NO: 125.

[0344] In some embodiments, the multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 126, an anti-STEAP1 light chain comprising SEQ ID NO: 127, an anti-CD3 heavy chain comprising SEQ ID NO: 128, and an anti-CD3 light chain comprising SEQ ID NO: 129.

[0345] In some embodiments, the multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 130, an anti-STEAP1 light chain comprising SEQ ID NO: 131, an anti-CD3 heavy chain comprising SEQ ID NO: 132, and an anti-CD3 light chain comprising SEQ ID NO: 133.

[0346] In some embodiments, the multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 134, an anti-STEAP1 light chain comprising SEQ ID NO: 135, an anti-CD3 heavy chain comprising SEQ ID NO: 136, and an anti-CD3 light chain comprising SEQ ID NO: 137.

[0347] In some embodiments, the multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 138, an anti-STEAP1 light chain comprising SEQ ID NO: 139, an anti-CD3 heavy chain comprising SEQ ID NO: 140, and an anti-CD3 light chain comprising SEQ ID NO: 141.

[0348] In some embodiments, the multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 142, an anti-STEAP1 light chain comprising SEQ ID NO: 143, an anti-CD3 heavy chain comprising SEQ ID NO: 144, and an anti-CD3 light chain comprising SEQ ID NO: 145.

[0349] In some embodiments, the multispecific antigen-binding molecule further comprises a third antigen-binding domain. The third antigen-binding domain can be an antigen expressed on the surface of a cell. The antigen can be expressed on the surface of cells obtained from a solid tumor. The antigen can be expressed on the surface of cells of prostate cancer, Ewing's sarcoma, lung cancer, colorectal cancer, breast cancer, bladder cancer, ovarian cancer, or cervical cancer.

[0350] In some embodiments, the antigen is a tumor-associated antigen (TAA). The TAA can be a receptor expressed on the surface of cells of prostate cancer, Ewing's sarcoma, lung cancer, colorectal cancer, breast cancer, bladder cancer, ovarian cancer, or cervical cancer. In some cases, the TAA is a receptor expressed on the surface of prostate cancer cells. In some instances, the TAA is a receptor expressed on Ewing's sarcoma cells. Exemplary tumor-associated antigens include, but are not limited to, prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), epithelial cell adhesion molecule (EpCAM), prostate-specific antigen (PSA), prostate acid phosphatase (PAP), STEAP2, and HBA-71.

[0351] In some cases, the multispecific antigen-binding molecule further comprises a third antigen-binding domain that binds to a tumor-associated antigen. In some cases, the third antigen-binding domain binds to a TAA of prostate cancer, Ewing sarcoma, lung cancer, colorectal cancer, breast cancer, bladder cancer, ovarian cancer, or cervical cancer. In some cases, the third antigen-binding domain binds to prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), epithelial cell adhesion molecule (EpCAM), prostate-specific antigen (PSA), prostate acid phosphatase (PAP), STEAP2, or HBA-71. In some cases, the third antigen-binding domain binds to PSMA. In some cases, the third antigen-binding domain binds to PSCA. In some cases, the third antigen-binding domain binds to EpCAM. In some cases, the third antigen-binding domain binds to PSA. In some cases, the third antigen-binding domain binds to PAP. In some cases, the third antigen-binding domain binds to STEAP2. In some cases, the third antigen-binding domain binds to HBA-71.

[0352] In some embodiments, the multispecific antigen-binding molecule has a K that is less than 100 nM, less than 75 nM, less than 50 nM, less than 40 nM, less than 30 nM, less than 20 nM, less than 10 nM, less than 1 nM, or lower D for binding to human STEAP1.

[0353] In some embodiments, the multispecific antigen-binding molecule has the following K DBinds to human STEAP1: from about 1 nM to about 100 nM, from about 1 nM to about 75 nM, from about 1 nM to about 50 nM, from about 1 nM to about 40 nM, from about 1 nM to about 30 nM, from about 1 nM to about 20 nM, from about 1 nM to about 10 nM, from about 1 nM to about 5 nM, from about 5 nM to about 100 nM, from about 5 nM to about 75 nM, from about 5 nM to about 50 nM, from about 5 nM to about 40 nM, from about 5 nM to about 30 nM, from about 5 nM to about 20 nM, from about 5 nM to about 10 nM, from about 10 nM to about 100 nM, from about 10 nM to about 75 nM, from about 10 nM to about 50 nM, from about 10 nM to about 40 nM, from about 10 nM to about 30 nM, from about 10 nM to about 20 nM, from about 15 nM to about 100 nM, from about 15 nM to about 75 nM, from about 15 nM to about 50 nM, from about 15 nM to about 40 nM, from about 15 nM to about 30 nM, from about 15 nM to about 20 nM, from about 20 nM to about 100 nM, from about 20 nM to about 75 nM, from about 20 nM to about 50 nM, from about 20 nM to about 40 nM, from about 20 nM to about 30 nM, from about 25 nM to about 100 nM, from about 25 nM to about 75 nM, from about 25 nM to about 50 nM, from about 25 nM to about 40 nM, from about 25 nM to about 30 nM, from about 30 nM to about 100 nM, from about 30 nM to about 75 nM, from about 30 nM to about 50 nM, from about 30 nM to about 40 nM, from about 35 nM to about 100 nM, from about 35 nM to about 75 nM, from about 35 nM to about 50 nM, from about 35 nM to about 40 nM, from about 40 nM to about 100 nM, from about 40 nM to about 75 nM, from about 40 nM to about 50 nM, from about 45 nM to about 100 nM, from about 45 nM to about 75 nM, from about 45 nM to about 50 nM, from about 50 nM to about 100 nM, from about 50 nM to about 75 nM,

[0354] From about 70 nM to about 100 nM, from about 70 nM to about 75 nM, from about 80 nM to about 100 nM, or from about 90 nM to about 100 nM. In some embodiments, the multispecific antigen-binding molecule has a K of 1 nM, about 2 nM, about 3 nM, about 4 nM, about 5 nM, about 6 nM, about 7 nM, about 8 nM, about 9 nM, about 10 nM, about 11 nM, about 12 nM, about 13 nM, about 14 nM, about 15 nM, about 16 nM, about 17 nM, about 18 nM, about 19 nM, about 20 nM, about 21 nM, about 22 nM, about 23 nM, about 24 nM, about 25 nM, about 26 nM, about 27 nM, about 28 nM, about 29 nM, about 30 nM, about 31 nM, about 32 nM, about 33 nM, about 34 nM, about 35 nM, about 36 nM, about 37 nM, about 38 nM, about 39 nM, about 40 nM, about 41 nM, about 42 nM, about 43 nM, about 44 nM, about 45 nM, about 46 nM, about 47 nM, about 48 nM, about 49 nM, or about 50 nM D and binds to human STEAP1 with a K of, in some embodiments, about 29 nM. D and binds to human STEAP1. In some embodiments, the K D is determined using a kinetic exclusion assay (KinExA®), as described, for example, in Example 8.

[0355] In some embodiments, the multispecific antigen-binding molecule has a K of less than 100 nM, less than 75 nM, less than 50 nM, less than 40 nM, less than 30 nM, less than 20 nM, less than 10 nM, less than 1 nM, or lower and binds to cyno STEAP1. D

[0356] In some embodiments, the multispecific antigen-binding molecule has the following K DBinds to cyno STEAP1 at: about 1 nM to about 100 nM, about 1 nM to about 75 nM, about 1 nM to about 50 nM, about 1 nM to about 40 nM, about 1 nM to about 30 nM, about 1 nM to about 20 nM, about 1 nM to about 10 nM, about 1 nM to about 5 nM, about 5 nM to about 100 nM, about 5 nM to about 75 nM, about 5 nM to about 50 nM, about 5 nM to about 40 nM, about 5 nM to about 30 nM, about 5 nM to about 20 nM, about 5 nM to about 10 nM, about 10 nM to about 100 nM, about 10 nM to about 75 nM, about 10 nM to about 50 nM, about 10 nM to about 40 nM, about 10 nM to about 30 nM, about 10 nM to about 20 nM, about 15 nM to about 100 nM, about 15 nM to about 75 nM, about 15 nM to about 50 nM, about 15 nM to about 40 nM, about 15 nM to about 30 nM, about 15 nM to about 20 nM, about 20 nM to about 100 nM, about 20 nM to about 75 nM, about 20 nM to about 50 nM, about 20 nM to about 40 nM, about 20 nM to about 30 nM, about 25 nM to about 100 nM, about 25 nM to about 75 nM, about 25 nM to about 50 nM, about 25 nM to about 40 nM, about 25 nM to about 30 nM, about 30 nM to about 100 nM, about 30 nM to about 75 nM, about 30 nM to about 50 nM, about 30 nM to about 40 nM, about 35 nM to about 100 nM, about 35 nM to about 75 nM, about 35 nM to about 50 nM, about 35 nM to about 40 nM, about 40 nM to about 100 nM, about 40 nM to about 75 nM, about 40 nM to about 50 nM, about 45 nM to about 100 nM, about 45 nM to about 75 nM, about 45 nM to about 50 nM, about 50 nM to about 100 nM, about 50 nM to about 75 nM,

[0357] about 70 nM to about 100 nM, about 70 nM to about 75 nM, about 80 nM to about 100 nM, or about 90 nM to about 100 nM. In some embodiments, the multispecific antigen-binding molecule has a K of 1 nM, about 2 nM, about 3 nM, about 4 nM, about 5 nM, about 6 nM, about 7 nM, about 8 nM, about 9 nM, about 10 nM, about 11 nM, about 12 nM, about 13 nM, about 14 nM, about 15 nM, about 16 nM, about 17 nM, about 18 nM, about 19 nM, about 20 nM, about 21 nM, about 22 nM, about 23 nM, about 24 nM, or about 25 nM D and binds to cyno STEAP1. In some embodiments, the multispecific antigen-binding molecule has a K of about 14 nM DIt binds to cyno STEAP1. In some embodiments, K D is determined using, for example, a kinetic exclusion assay (KinExA®) as described in Example 8.

[0358] In some embodiments, the multispecific antigen-binding molecule has a C max of up to or about 15, 20, 25, or 30 μg / mL. In some cases, the multispecific antigen-binding molecule has a C max of about 11, 11.5, 12, 12.1, 12.6, 13, 13.2, 13.5, 15, 15.3, 18, 20, 23.4, 25, 27.9, 29.1 or 30 μg / mL.

[0359] In some embodiments, the multispecific antigen-binding molecule has a concentration of from about 10 μg / mL to about 30 μg / mL (e.g., from about 10 μg / mL to about 30 μg / mL, from about 10 μg / mL to about 28 μg / mL, from about 10 μg / mL to about 26 μg / mL, from about 10 μg / mL to about 24 μg / mL, from about 10 μg / mL to about 22 μg / mL, from about 10 μg / mL to about 20 μg / mL, from about 10 μg / mL to about 18 μg / mL, from about 10 μg / mL to about 16 μg / mL, from about 10 μg / mL to about 14 μg / mL, from about 10 μg / mL to about 12 μg / mL, from about 12 μg / mL to about 30 μg / mL, from about 12 μg / mL to about 28 μg / mL, from about 12 μg / mL to about 26 μg / mL, from about 12 μg / mL to about 24 μg / mL, from about 12 μg / mL to about 22 μg / mL, from about 12 μg / mL to about 20 μg / mL, from about 12 μg / mL to about 18 μg / mL, from about 12 μg / mL to about 16 μg / mL, from about 12 μg / mL to about 14 μg / mL, from about 14 μg / mL to about 30 μg / mL, from about 14 μg / mL to about 28 μg / mL, from about 14 μg / mL to about 26 μg / mL, from about 14 μg / mL to about 24 μg / mL, from about 14 μg / mL to about 22 μg / mL, from about 14 μg / mL to about 20 μg / mL, from about 14 μg / mL to about 18 μg / mL, from about 14 μg / mL to about 16 μg / mL, from about 16 μg / mL to about 30 μg / mL, from about 16 μg / mL to about 28 μg / mL, from about 16 μg / mL to about 26 μg / mL, from about 16 μg / mL to about 24 μg / mL, from about 16 μg / mL to about 22 μg / mL, from about 16 μg / mL to about 20 μg / mL, from about 16 μg / mL to about 18 μg / mL, from about 18 μg / mL to about 30 μg / mL, from about 18 μg / mL to about 28 μg / mL, from about 18 μg / mL to about 26 μg / mL, from about 18 μg / mL to about 24 μg / mL, from about 18 μg / mL to about 22 μg / mL, from about 18 μg / mL to about 20 μg / mL, from about 20 μg / mL to about 30 μg / mL, from about 20 μg / mL to about 28 μg / mL, from about 20 μg / mL to about 26 μg / mL, from about 20 μg / mL to about 24 μg / mL, from about 20 μg / mL to about 22 μg / mL, from about 22 μg / mL to about 30 μg / mL, from about 22 μg / mL to about 28 μg / mL, from about 22 μg / mL to about 26 μg / mL, from about 22 μg / mL to about 24 μg / mL, from about 24 μg / mL to about 30 μg / mL, from about 24 μg / mL to about 28 μg / mL, from about 22 μg / mL to about 26 μg / mL, from about 22 μg / mL to about 24 μg / mL,C of about 26 μg / mL to about 30 μg / mL, about 26 μg / mL to about 28 μg / mL, or about 28 μg / mL to about 30 μg / mL max In some embodiments, the multispecific antigen-binding molecule has a C of about 20 μg / mL to about 28 μg / mL (e.g., about 20 μg / mL, about 21 μg / mL, about 22 μg / mL, about 23 μg / mL, about 24 μg / mL, about 25 μg / mL, about 26 μg / mL, about 27 μg / mL, or about 28 μg / mL). max In some embodiments, the multispecific antigen-binding molecule has a C of about 24 μg / mL. max In some embodiments, C max can be determined as described in Example 9 (female SCID mice). In some embodiments, C max can be determined as described in Example 10 (cynomolgus monkeys).

[0360] In some embodiments, the multispecific antigen-binding molecule has an EC of about 0.6, 0.56, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.09, 0.05, or less. 50 In some cases, the multispecific antigen-binding molecule has an EC of about 0.5 or less. 50 In some cases, the multispecific antigen-binding molecule has an EC of about 0.4 or less. 50 In some cases, the multispecific antigen-binding molecule has an EC of about 0.3 or less. 50 In some cases, the multispecific antigen-binding molecule has an EC of about 0.2 or less. 50 In some cases, the multispecific antigen-binding molecule has an EC of about 0.1 or less. 50 In some cases, the multispecific antigen-binding molecule has an EC of about 0.1 or less.

[0361] In some embodiments, the multispecific antigen-binding molecule has a valency of from about 0.05 to about 0.8 (e.g., from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.70, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.05 to about 0.09, from about 0.05 to about 0.08, from about 0.05 to about 0.07, from about 0.05 to about 0.06, from about 0.06 to about 0.8, from about 0.06 to about 0.75, from about 0.06 to about 0.70, from about 0.06 to about 0.65, from about 0.06 to about 0.6, from about 0.06 to about 0.55, from about 0.06 to about 0.5, from about 0.06 to about 0.45, from about 0.06 to about 0.4, from about 0.06 to about 0.35, from about 0.06 to about 0.3, from about 0.06 to about 0.25, from about 0.06 to about 0.2, from about 0.06 to about 0.15, from about 0.06 to about 0.1, from about 0.06 to about 0.09, from about 0.06 to about 0.08, from about 0.06 to about 0.07, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.70, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.07 to about 0.09, from about 0.07 to about 0.08, from about 0.08 to about 0.8, from about 0.08 to about 0.75, from about 0.08 to about 0.70, from about 0.08 to about 0.65, from about 0.08 to about 0.6, from about 0.08 to about 0.55, from about 0.08 to about 0.5, from about 0.08 to about 0.45, from about 0.08 to about 0.4, from about 0.08 to about 0.35, from about 0.08 to about 0.3, from about 0.08 to about 0.25, from about 0.08 to about 0.2, from about 0.08 to about 0.15, from about 0.08 to about 0.1, from about 0.08 to about 0.09, from about 0.09 to about 0.8, from about 0.09 to about 0.75, from about 0.09 to about 0.70, from about 0.09 to about 0.65, from about 0.09 to about 0.6, from about 0.09 to about 0.55, from about 0.09 to about 0.5, from about 0.09 to about 0.45, from about 0.09 to about 0.4, from about 0.09 to about 0.35, from about 0.09 to about 0.3, from about 0.09 to about 0.25, from about 0.09 to about 0.2. From about 0.09 to about 0.15, from about 0.09 to about 0.1, from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.70, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.15 to about 0.8, from about 0.15 to about 0.75, from about 0.15 to about 0.70, from about 0.15 to about 0.65, from about 0.15 to about 0.6, from about 0.15 to about 0.55, from about 0.15 to about 0.5, from about 0.15 to about 0.45, from about 0.15 to about 0.4, from about 0.15 to about 0.35, from about 0.15 to about 0.3, from about 0.15 to about 0.25, from about 0.15 to about 0.2, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.70, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.25 to about 0.8, from about 0.25 to about 0.75, from about 0.25 to about 0.70, from about 0.25 to about 0.65, from about 0.25 to about 0.6, from about 0.25 to about 0.55, from about 0.25 to about 0.5, from about 0.25 to about 0.45, from about 0.25 to about 0.4, from about 0.25 to about 0.35, from about 0.25 to about 0.3, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.70, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.35 to about 0.8, from about 0.35 to about 0.75, from about 0.35 to about 0.70, from about 0.35 to about 0.65, from about 0.35 to about 0.6, from about 0.35 to about 0.55, from about 0.35 to about 0.5, from about 0.35 to about 0.45, from about 0.35 to about 0.4, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.70, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.45 to about 0.8, from about 0.45 to about 0.75, from about 0.45 to about 0.70, from about 0.45 to about 0.65, from about 0.45 to about 0.6, from about 0.45 to about 0.55, from about 0.45 to about 0.5, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.70, from about 0.5 to about 0.65, from about 0.EC of 5 to about 0.6, about 0.5 to about 0.55, about 0.55 to about 0.8, about 0.55 to about 0.75, about 0.55 to about 0.70, about 0.55 to about 0.65, about 0.55 to about 0.6, about 0.6 to about 0.8, about 0.6 to about 0.75, about 0.6 to about 0.70, about 0.6 to about 0.65, about 0.65 to about 0.8, about 0.65 to about 0.75, about 0.65 to about 0.70, about 0.7 to about 0.8, about 0.7 to about 0.75, or about 0.75 to about 0.8). 50 has

[0362] In some embodiments, the EC 50 is determined in a 72-hour cell killing assay using human CD8+ T cells and STEAP1-expressing LNCaP-X1.2 cells. In some embodiments, the EC 50 is from about 0.05 to about 0.4 (e.g., about 0.05, about 0.06, about 0.07, about 0.08, about 0.09, about 0.1, about 0.15, about 0.2, about 0.25, about 0.3, about 0.35, or about 0.4). In some embodiments, the EC 50 is about 0.08 or about 0.3. In some embodiments, the EC 50 is about 0.08. In some embodiments, the EC 50 is about 0.3.

[0363] In some embodiments, the EC 50 is determined in a 72-hour cell killing assay using human CD8+ T cells and STEAP1-expressing LNCaP X1.2KO3-13 cells. In some embodiments, the EC 50 is from about 0.1 to about 0.8 (e.g., about 0.1, about 0.15, about 0.2, about 0.25, about 0.3, about 0.35, about 0.4, about 0.45, about 0.5, about 0.55, about 0.6, about 0.65, about 0.7, about 0.75, or about 0.8). In some embodiments, the EC 50 is about 0.1 or about 0.7. In some embodiments, the EC 50 is about 0.1. In some embodiments, the EC 50 is about 0.7.

[0364] In some embodiments, the multispecific antigen-binding molecule binds monovalently to STEAP1. In other embodiments, the multispecific antigen-binding molecule binds polyvalently (e.g., bivalently) to STEAP1.

[0365] An antibody that binds to a specific STEAP1 epitope In certain embodiments, the antibody of the invention comprises a first antigen-binding domain that binds to the STEAP1 protein. In some cases, the first antigen-binding domain binds to the human STEAP1 protein. In other cases, the first antigen-binding domain binds to a primate STEAP1 protein, such as a STEAP1 protein from cynomolgus monkey or Pongo abelii.

[0366] In some embodiments, the antibody comprises a first antigen-binding domain that binds to human STEAP1 at one or more residues selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281, wherein residue positions 101, 102, 103, 195, 198, 202, and 281 correspond to positions 101, 102, 103, 195, 198, 202, and 281 shown in SEQ ID NO: 65. In some cases, the first antigen-binding domain binds to at least one residue selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of SEQ ID NO: 65.

[0367] In some cases, residues from the first antigen-binding domain form a hydrogen bond with at least one residue selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281. In some cases, at least one residue selected from Leu56, Ser73, Asn74, Gly101, Tyr103, and Tyr107 of the VH of the first antigen-binding domain forms a hydrogen bond with at least one residue selected from Ser101, His102, Gln103, Trp195, Gln198, Gln202, and Lys281 of STEAP1, and residue positions 56, 73, 74, 101, 103, and 107 correspond to positions 56, 73, 74, 101, 103, and 107 shown in SEQ ID NO: 18. In some cases, at least one residue selected from Tyr35 or Tyr54 of the VL of the first antigen-binding domain forms a hydrogen bond with at least one residue selected from Gln202 or Gln201, and residue positions 35 and 54 correspond to positions 35 and 54 shown in SEQ ID NO: 8. In some cases, residues Asn203 and / or Lys204 of human STEAP1 form van der Waals interactions with one or more VL CDR residues. In some cases, the residues forming the hydrogen bond are as shown in Table 3.

Table 3

[0368] In some embodiments, the antibody of the invention is a monospecific antibody as described above under Section A "Antigen-Binding Molecules That Bind to STEAP1". In some cases, the antibody comprises a VH region comprising CDR-H1, CDR-H2, and CDR-H3 of a VH sequence selected from SEQ ID NOs: 7, 17-25, 30-34, 38, and 68; and a VL region comprising CDR-L1, CDR-L2, and CDR-L3 of a VL sequence selected from SEQ ID NOs: 8, 26-29, 39, and 69. In some cases, the antibody comprises six CDRs, CDR-H1 is Xaa 1 Xaa 2comprising YMA (SEQ ID NO: 35); wherein, Xaa 1 is Asp (D) or Asn (N); and Xaa 2 is His (H), Tyr (Y), or Phe (F); CDR-H2 comprises YIXaa 3 YDGXaa 4 Xaa 5 TXaa 6 and comprises YGDSVKG (SEQ ID NO: 36); wherein, Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D), or Leu (L); Xaa 5 is Ser (S), Asp (D), or Asn (N); and Xaa 6 is Ser (S) or Tyr (Y); CDR-H3 comprises RSGXaa 7 YHVGYAMXaa 8 Xaa 9 and comprises (SEQ ID NO: 37); wherein, Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6.

[0369] In some cases, the antibody comprises six CDRs, CDR-H1 comprises GFTFSXaa 10 Xaa 11 and comprises (SEQ ID NO: 63); In the formula, Xaa 10 is Asn (N) or Asp (D); and Xaa 11 is Tyr (Y), Phe (F) or His (H); CDR-H2 contains Xaa 12 YDGXaa 13 Xaa 14 (SEQ ID NO: 64); In the formula, Xaa 12 is Asp (D) or Ser (S); Xaa 13 is Gly (G), Asp (D) or Leu (L); and Xaa 14 is Ser (S), Asp (D) or Asn (N); CDR-H3 contains RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); In the formula, Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 contains the amino acid sequence of SEQ ID NO: 4; CDR-L2 contains the amino acid sequence of SEQ ID NO: 5; and CDR-L3 contains the amino acid sequence of SEQ ID NO: 6.

[0370] In some embodiments, the antibody of the invention is a multispecific antibody as described above under Section B, "Multispecific Antigen-Binding Molecules". In some cases, the antibody comprises (A) an anti-STEAP1 heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and / or CDR-H3 of a VH sequence selected from SEQ ID NOs: 7, 17-25, 30-34, 38, and 68; and / or an anti-STEAP1 light chain variable region (VL) that binds to STEAP1 and comprises CDR-L1, CDR-L2, and / or CDR-L3 of a VL sequence selected from SEQ ID NOs: 8, 26-29, 39, and 69, as a first antigen-binding domain; and (B) a second antigen-binding domain that binds to a T cell receptor (e.g., CD3).

[0371] In some cases, the antibody comprises (A) an anti-STEAP1 heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3; and an anti-STEAP1 light chain variable region (VL) that binds to STEAP1 and comprises CDR-L1, CDR-L2, and CDR-L3, as a first antigen-binding domain; wherein CDR-H1 comprises 1 Xaa 2 YMA (SEQ ID NO: 35); wherein Xaa 1 is Asp (D) or Asn (N); and Xaa 2 is His (H), Tyr (Y), or Phe (F); CDR-H2 comprises 3 YIXaa 4 YDGXaa 5 Xaa 6 TXaa wherein Xaa 3 is Asp (D) or Ser (S); Xaa 4 is Gly (G), Asp (D), or Leu (L); Xaa 5 is Ser (S), Asp (D), or Asn (N); and Xaa 6 is Ser (S) or Tyr (Y); and CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe (F) or Tyr (Y); Xaa 8 is Asn (N) or Asp (D); and Xaa 9 is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor (e.g., CD3).

[0372] In some embodiments, the antibody comprises (A) a first antigen-binding domain that binds to STEAP1 and comprises an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3; and an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3; where CDR-H1 is GFTFSXaa 10 Xaa 11 (SEQ ID NO: 63); wherein Xaa 10 is Asn (N) or Asp (D); and Xaa 11 is Tyr (Y), Phe (F), or His (H); CDR-H2 is Xaa 12 YDGXaa 13 Xaa 14 (SEQ ID NO: 64); wherein Xaa 12is Asp(D) or Ser(S); Xaa 13 is Gly(G), Asp(D) or Leu(L); and Xaa 14 is Ser(S), Asp(D) or Asn(N); CDR-H3 is RSGXaa 7 YHVGYAMXaa 8 Xaa 9 (SEQ ID NO: 37); wherein Xaa 7 is Phe(F) or Tyr(Y); Xaa 8 is Asn(N) or Asp(D); and Xaa 9 is Ala(A) or Gly(G); CDR-L1 contains the amino acid sequence of SEQ ID NO: 4; CDR-L2 contains the amino acid sequence of SEQ ID NO: 5; and / or CDR-L3 contains the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor (e.g., CD3).

[0373] A peptide linker that fuses the first and second antigen-binding domains In some embodiments, the multispecific antigen-binding molecule of the invention (e.g., a bispecific or trispecific antigen-binding molecule) features a structure in which the C-terminus of the first antigen-binding domain is fused via a peptide linker to the N-terminus of the second antigen-binding domain. The peptide linker can be 5 to 20 amino acids in length (e.g., 5 to 10, 10 to 15, or 15 to 20, such as 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids in length). In some embodiments, the peptide linker contains the native amino acid sequence of the variable heavy chain hinge region (e.g., DKTHT). In some embodiments, the peptide linker is (Gly4Ser) n linker (or (G4S) ncomprising a linker), wherein n is 1 to 10, 2 to 10, 3 to 10, 4 to 10, 5 to 10, 6 to 10, 2 to 6, 2 to 6, 3 to 6, or 4 to 6. In some cases, n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, the peptide linker comprises a G4SG2 linker. In some embodiments, the peptide linker comprises a G4SG2 linker and a hinge region (e.g., DKTHT). In some embodiments, the peptide linker comprises a plurality of glycines, alanines, or combinations thereof.

[0374] Fc domain The antigen-binding molecules of the present invention (e.g., monospecific and / or multispecific antigen-binding molecules, e.g., bispecific or trispecific antigen-binding molecules) may be characterized by an Fc domain. The Fc domain may be an IgG Fc domain (e.g., IgG1, IgG2 or IgG4 Fc domain). For example, the Fc domain may be a human Fc domain. In some embodiments, the Fc domain comprises one or more amino acid substitutions that reduce binding to Fc receptors and / or effector functions. For example, in some embodiments, the one or more amino acid substitutions that reduce binding to Fc receptors and / or effector functions are at one or more positions selected from the group consisting of L234, L235, and P329 (e.g., the first Fc subunit and the second Fc subunit each comprise the amino acid substitutions L234A, L235A, and P329G). The Fc receptor may be, for example, an Fcγ receptor. Thus, the antigen-binding molecules of the present invention (e.g., monospecific and / or multispecific antigen-binding molecules, e.g., bispecific or trispecific antigen-binding molecules) can be configured to reduce antibody-dependent cell-mediated cytotoxicity (ADCC).

[0375] In some cases, the Fc domain includes modifications configured to promote the association of a first Fc subunit with a second Fc subunit. The "knob-in-hole" engineering of bispecific antibodies may be utilized to generate a first arm containing a knob and a second arm containing a hole to which the knob of the first arm binds. The knob of the multispecific antigen-binding molecule of the present invention can be, in one embodiment, an anti-STEAP1 arm. Alternatively, the knob of the multispecific antigen-binding molecule of the present invention can be an anti-CD3 arm. The hole of the multispecific antigen-binding molecule of the present invention can be, in one embodiment, an anti-STEAP1 arm. Alternatively, the hole of the multispecific antigen-binding molecule of the present invention can be an anti-CD3 arm. Multispecific antigen-binding molecules such as bispecific antibodies may also be engineered using immunoglobulin crossover (also known as Fab domain exchange or CrossMab format) technology (see, e.g., WO2009 / 080253; Schaefer et al., Proc. Natl. Acad. Sci. USA, 108:11187-11192 (2011)). Multispecific antibodies may also be made by manipulating the electrostatic steering effect to create antibody Fc heterodimer molecules (WO2009 / 089004A1), by cross-linking two or more antibodies or fragments (see, e.g., U.S. Patent No. 4,676,980 and Brennan et al., Science, 229:81 (1985)); or by using leucine zippers for producing bispecific antibodies (see, e.g., Kostelny et al., J. Immunol., 148(5):1547-1553 (1992)).

[0376] By replacing the amino acid residues in the CH3 domain of the second Fc subunit with amino acid residues having a larger side chain volume, a protrusion (e.g., a knob) can be generated within the CH3 domain of the second Fc subunit that can be positioned within a cavity (e.g., a hole) in the CH3 domain of the first Fc subunit. By replacing the amino acid residues in the CH3 domain of the first Fc subunit with amino acid residues having a smaller side chain volume, a cavity (e.g., a hole) can be generated within the CH3 domain of the first Fc subunit that can be positioned within a protrusion (e.g., a knob) in the CH3 domain of the second Fc subunit. In some embodiments, the CH3 domain of the second Fc subunit comprises an amino acid substitution at T366, and the CH3 domain of the first Fc subunit comprises amino acid substitutions at one, two, or all three of T366, L368, and / or Y407 (all EU numbering). In some embodiments, the CH3 domain of the second Fc subunit comprises the amino acid substitution T366W, and the CH3 domain of the first Fc subunit comprises amino acid substitutions at one, two, or all three of T366S, L368A, and / or Y407V (all EU numbering).

[0377] In some embodiments, the multispecific antigen-binding molecule described herein comprises an anti-STEAP1 arm comprising N297G (EU numbering) and T366W (EU numbering) substitutions in the heavy chain, and an anti-CD3 arm comprising N297G (EU numbering), T366S (EU numbering), L368A (EU numbering), and Y407V (EU numbering) substitutions in the heavy chain. In some embodiments, the multispecific antigen-binding molecule described herein comprises an anti-STEAP1 arm comprising N297G (EU numbering) and T366W (EU numbering) substitutions in the heavy chain, and an anti-CD3 arm comprising N297G (EU numbering), T366S (EU numbering), L368A (EU numbering), and Y407V (EU numbering) substitutions in the heavy chain.

[0378] In some embodiments, the multispecific antigen-binding molecules described herein comprise: a) a first heavy chain / light chain pair that binds to a first antigen comprising a first heavy chain polypeptide (H1) and a first light chain polypeptide (L1); and b) a second heavy chain / light chain pair that binds to a second antigen comprising a second heavy chain polypeptide (H2) and a second light chain polypeptide (L2), wherein each H1 and H2 comprises a heavy chain variable domain (VH) and a heavy chain constant domain (CH1), and each L1 and L2 comprises a light chain variable domain (VL) and a light chain constant domain (CL), and (i) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with a positively charged residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with a negatively charged residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with a negatively charged residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with a positively charged residue; and the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with a positively charged residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with a negatively charged residue; or (ii) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with a negatively charged residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with a positively charged residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with a positively charged residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with a negatively charged residue; and the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with a negatively charged residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with a positively charged residue. In some embodiments, the positively charged residue is selected from R and K, and the negatively charged residue is selected from D and E. In some embodiments, the positively charged residue is R. In other embodiments, the positively charged residue is K.In some embodiments, the negatively charged residue is D. In other embodiments, the negatively charged residue is E. In some embodiments, the first antigen is STEAP1 and the second antigen is CD3. In other embodiments, the first antigen is CD3 and the second antigen is STEAP1.

[0379] For example, in some embodiments, the multispecific antigen-binding molecule described herein comprises an anti-STEAP1 arm comprising a first heavy chain polypeptide (H1) and a first light chain polypeptide (L1), and an anti-CD3 arm comprising a second heavy chain polypeptide (H2) and a second light chain polypeptide (L2), wherein each of H1 and H2 comprises a heavy chain variable domain (VH) and a heavy chain constant domain (CH1), and each of L1 and L2 comprises a light chain variable domain (VL) and a light chain constant domain (VL), and (i) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with an R or K residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with a D or E residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with a D or E residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with an R or K residue; the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with an R or K residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with a D or E residue; or (ii) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with a D or E residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with an R or K residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with an R or K residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with a D or E residue; the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with a D or E residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with an R or K residue.

[0380] In some embodiments, the multispecific antigen-binding molecules described herein comprise an anti-STEAP1 arm comprising a first heavy chain polypeptide (H1) and a first light chain polypeptide (L1), and an anti-CD3 arm comprising a second heavy chain polypeptide (H2) and a second light chain polypeptide (L2), wherein each H1 and H2 comprises a heavy chain variable domain (VH) and a heavy chain constant domain (CH1), and each L1 and L2 comprises a light chain variable domain (VL) and a light chain constant domain (VL), and (i) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with a K residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with an E residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with an E residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with a K residue; the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with a K residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with an E residue; or (ii) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with an E residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with a K residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with a K residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with an E residue; the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with an E residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with a K residue.

[0381] For example, in other embodiments, the multispecific antigen-binding molecule described herein comprises an anti-CD3 arm comprising a first heavy chain polypeptide (H1) and a first light chain polypeptide (L1), and an anti-STEAP1 arm comprising a second heavy chain polypeptide (H2) and a second light chain polypeptide (L2), wherein each of H1 and H2 comprises a heavy chain variable domain (VH) and a heavy chain constant domain (CH1), and each of L1 and L2 comprises a light chain variable domain (VL) and a light chain constant domain (VL), and (i) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with an R or K residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with a D or E residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with a D or E residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with an R or K residue; the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with an R or K residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with a D or E residue; or (ii) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with a D or E residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with an R or K residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with an R or K residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with a D or E residue; the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with a D or E residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with an R or K residue.

[0382] In some embodiments, the multispecific antigen-binding molecules described herein comprise an anti-CD3 arm comprising a first heavy chain polypeptide (H1) and a first light chain polypeptide (L1), and an anti-STEAP1 arm comprising a second heavy chain polypeptide (H2) and a second light chain polypeptide (L2), wherein each H1 and H2 comprises a heavy chain variable domain (VH) and a heavy chain constant domain (CH1), and each L1 and L2 comprises a light chain variable domain (VL) and a light chain constant domain (VL), and (i) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with a K residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with an E residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with an E residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with a K residue; the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with a K residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with an E residue; or (ii) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with an E residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with a K residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with a K residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with an E residue; the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with an E residue, and the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with a K residue.

[0383] In some embodiments, the multispecific antigen-binding molecules described herein comprise an anti-STEAP1 arm with Q39K (Kabat numbering) and S183E (EU numbering) substitutions in the heavy chain and Q38E (Kabat numbering) and V133K (EU numbering) substitutions in the light chain, and an anti-CD3 arm with Q39E (Kabat numbering) substitution in the heavy chain and Q38K (Kabat numbering) substitution in the light chain.

[0384] In some embodiments, the multispecific antigen-binding molecules described herein comprise an anti-CD3 arm with Q39K (Kabat numbering) and S183E (EU numbering) substitutions in the heavy chain and Q38E (Kabat numbering) and V133K (EU numbering) substitutions in the light chain, and an anti-STEAP1 arm with Q39E (Kabat numbering) substitution in the heavy chain and Q38K (Kabat numbering) substitution in the light chain.

[0385] In some embodiments, the multispecific antigen-binding molecules described herein comprise an anti-STEAP1 arm with Q39E (Kabat numbering) and S183K (EU numbering) substitutions in the heavy chain and Q38K (Kabat numbering) and V133E (EU numbering) substitutions in the light chain, and an anti-CD3 arm with Q39K (Kabat numbering) substitution in the heavy chain and Q38E (Kabat numbering) substitution in the light chain.

[0386] In some embodiments, the multispecific antigen-binding molecules described herein comprise an anti-CD3 arm with Q39E (Kabat numbering) and S183K (EU numbering) substitutions in the heavy chain and Q38K (Kabat numbering) and V133E (EU numbering) substitutions in the light chain, and an anti-STEAP1 arm with Q39K (Kabat numbering) substitution in the heavy chain and Q38E (Kabat numbering) substitution in the light chain.

[0387] In some embodiments, the multispecific antigen-binding molecules described herein comprise: a) a first heavy chain / light chain pair that binds to a first antigen comprising a first heavy chain polypeptide (H1) and a first light chain polypeptide (L1), and b) a second heavy chain / light chain pair that binds to a second antigen comprising a second heavy chain polypeptide (H2) and a second light chain polypeptide (L2), wherein each H1 and H2 comprises a heavy chain variable domain (VH) and a heavy chain constant domain (CH1), and each L1 and L2 comprises a light chain variable domain (VL) and a light chain constant domain (CL), and (i) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with a positively charged residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with a negatively charged residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with a negatively charged residue, the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with a positively charged residue, the amino acid at S183 (EU numbering) in the CH1 domain of H2 is replaced with a negatively charged residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with a positively charged residue, the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with a negatively charged residue, and the amino acid at V133 (EU numbering) in the CL domain of L2 is replaced with a positively charged residue;or (ii) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with a negatively charged residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with a positively charged residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with a positively charged residue, the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with a negatively charged residue, the amino acid at S183 (EU numbering) in the CH1 domain of H2 is replaced with a positively charged residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with a negatively charged residue, the amino acid at Q38 (Kabat numbering) in the VL domain of L2 is replaced with a positively charged residue, and the amino acid at V133 (EU numbering) in the CL domain of L2 is replaced with a negatively charged residue. In some embodiments, the positively charged residue is selected from R and K, and the negatively charged residue is selected from D and E. In some embodiments, the positively charged residue is R. In other embodiments, the positively charged residue is K. In some embodiments, the negatively charged residue is D. In other embodiments, the negatively charged residue is E. In some embodiments, the first antigen is STEAP1 and the second antigen is CD3. In other embodiments, the first antigen is CD3 and the second antigen is STEAP1.;

[0388] For example, in some embodiments, the multispecific antigen-binding molecules described herein include an anti-STEAP1 arm comprising a first heavy chain polypeptide (H1) and a first light chain polypeptide (L1), and an anti-CD3 arm comprising a second heavy chain polypeptide (H2) and a second light chain polypeptide (L2), wherein each of H1 and H2 comprises a heavy chain variable domain (VH) and a heavy chain constant domain (CH1), and each of L1 and L2 comprises a light chain variable domain (VL) and a light chain constant domain (CL), and (i) the amino acid at S183 (EU numbering) in the CH1 domain of H1 is replaced with an R or K residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H1 is replaced with a D or E residue, the amino acid at V133 (EU numbering) in the CL domain of L1 is replaced with a D or E residue, the amino acid at Q38 (Kabat numbering) in the VL domain of L1 is replaced with an R or K residue, the amino acid at S183 (EU numbering) in the CH1 domain of H2 is replaced with a D or E residue, the amino acid at Q39 (Kabat numbering) in the VH domain of H2 is replaced with an R or K resi...

Claims

**Claim 1** A multispecific antigen-binding molecule comprising: (A) a heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3 of a VH sequence selected from SEQ ID NOs: 7, 17-25, 30-34, 38, and 68; and a light chain variable region (VL) that binds to STEAP1 and comprises CDR-L1, CDR-L2, and CDR-L3 of a VL sequence selected from SEQ ID NOs: 8, 26-29, 39, and 69, a first antigen-binding domain; and (B) a second antigen-binding domain that binds to a T cell receptor. **Claim 2** A multispecific antigen-binding molecule comprising: (A) a heavy chain variable region (VH) that binds to STEAP1 and comprises CDR-H1, CDR-H2, and CDR-H3, and a light chain variable region (VL) that binds to STEAP1 and comprises CDR-L1, CDR-L2, and CDR-L3, a first antigen-binding domain; wherein CDR-H1 is Xaa １ Xaa ２ includes YMA (SEQ ID NO: 35); in the formula Xaa １ is Asp(D) or Asn(N); and Xaa ２ is His (H), Tyr (Y), or Phe (F); CDR-H2 is YIXaa ３ YDGXaa ４ Xaa ５ TXaa ６ comprises YGDSSVK (SEQ ID NO: 36); in the formula Xaa ３ is Asp(D) or Ser(S); Xaa ４ is Gly (G), Asp (D) or Leu (L); Xaa ５ is Ser (S), Asp (D) or Asn (N); and Xaa ６ is Ser (S) or Tyr (Y); and CDR-H3 is RSGXaa ７ YHVGYAMXaa ８ Xaa ９ (SEQ ID NO: 37); in the formula Xaa ７ is Phe (F) or Tyr (Y); Xaa ８ is Asn (N) or Asp (D); and Xaa ９ is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6; and (B) a second antigen-binding domain that binds to a T cell receptor. **Claim 3** The multispecific antigen-binding molecule according to claim 1 or 2, wherein CDR-H1 comprises the amino acid sequence of SEQ ID NO: 10, 1, or 9. **Claim 4** The multispecific antigen-binding molecule according to any one of claims 1 to 3, wherein CDR-H2 comprises the amino acid sequence of SEQ ID NO: 2, 11, 12, or 13. **Claim 5** The multispecific antigen-binding molecule according to any one of claims 1 to 4, wherein CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15. **Claim 6** The multispecific antigen-binding molecule according to any one of claims 1 to 5, wherein the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 16; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO:

6. **Claim 7** The multispecific antigen-binding molecule according to any one of claims 1 to 5, wherein the first antigen-binding domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and A multispecific antigen-binding molecule comprising CDR-L3 comprising the amino acid sequence of SEQ ID NO:

6. **Claim 8** The multispecific antigen-binding molecule according to any one of claims 1 to 5, wherein the first antigen-binding domain CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 11; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and A multispecific antigen-binding molecule comprising CDR-L3 comprising the amino acid sequence of SEQ ID NO:

6. **Claim 9** The multispecific antigen-binding molecule according to any one of claims 1 to 5, wherein the first antigen-binding domain CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and A multispecific antigen-binding molecule comprising CDR-L3 comprising the amino acid sequence of SEQ ID NO:

6. **Claim 10** The multispecific antigen-binding molecule according to any one of claims 1 to 5, wherein the first antigen-binding domain CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and A multispecific antigen-binding molecule comprising CDR-L3 comprising the amino acid sequence of SEQ ID NO:

6. **Claim 11** The multispecific antigen-binding molecule according to any one of claims 1 to 5, wherein the first antigen-binding domain CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 13; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and A multispecific antigen-binding molecule comprising CDR-L3 comprising the amino acid sequence of SEQ ID NO:

6. **Claim 12** The multispecific antigen-binding molecule according to any one of claims 1 to 11, wherein the multispecific antigen-binding molecule is a humanized antibody.

13. The first antigen-binding domain and the second antigen-binding domain each independently include an IgG framework region and optionally an IgG １ or an IgG ４ framework region, the multispecific antigen-binding molecule according to any one of claims 1 to 12.

14. The multispecific antigen-binding molecule according to any one of claims 1 to 13, wherein the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68.

15. The multispecific antigen-binding molecule according to any one of claims 1 to 14, wherein the first antigen-binding domain comprises an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69.

16. The multispecific antigen-binding molecule according to any one of claims 1 to 15, wherein the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 68, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO:

69.

17. The multispecific antigen-binding molecule according to any one of claims 1 to 15, wherein the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 34, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO:

27.

18. The multispecific antigen-binding molecule according to any one of claims 1 to 15, wherein the first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 30, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO:

27.

19. The multispecific antigen-binding molecule according to any one of claims 1 to 15, wherein the first antigen-binding domain comprises an anti-STEAP1 heavy-chain variable region having a VH sequence with at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 31, and an anti-STEAP1 light-chain variable region having a VL sequence with at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

27.

20. The multispecific antigen-binding molecule according to any one of claims 1 to 15, wherein the first antigen-binding domain comprises an anti-STEAP1 heavy-chain variable region having a VH sequence with at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 32, and an anti-STEAP1 light-chain variable region having a VL sequence with at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

27.

21. The multispecific antigen-binding molecule according to any one of claims 1 to 15, wherein the first antigen-binding domain comprises an anti-STEAP1 heavy-chain variable region having a VH sequence with at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 33, and an anti-STEAP1 light-chain variable region having a VL sequence with at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

27.

22. The multispecific antigen-binding molecule according to any one of claims 1 to 21, wherein the T cell receptor is cluster of differentiation 3 (CD3).

23. The multispecific antigen-binding molecule according to claim 22, wherein the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy-chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light-chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3, and wherein the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the sequences of SEQ ID NOs: 48 to 53.

24. The multispecific antigen-binding molecule according to claim 23, wherein the second antigen-binding domain that binds to CD3 comprises a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 54, and a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

55.

25. The multispecific antigen-binding molecule according to claim 22, wherein the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3, and the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the sequences of SEQ ID NOs: 40-45.

26. The multispecific antigen-binding molecule according to claim 25, wherein the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 46, and an anti-CD3 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

47.

27. The multispecific antigen-binding molecule comprises one or more heavy chain constant domains, and the one or more heavy chain constant domains are a first CH1 (CH1 １ ), a first CH2 (CH2 １ ), a first CH3 (CH3 １ ), a second CH1 (CH1 ２ ), a second CH2 (CH2 ２ ), and a second CH3 (CH3 ２ ) domain, and the multispecific antigen-binding molecule according to any one of claims 1 to 26.

28. The multispecific antigen-binding molecule according to claim 27, wherein at least one of the one or more heavy chain constant domains is paired with another heavy chain constant domain.

29. said CH3 １ domain and said CH3 ２ domains each contain a protrusion or a cavity, and the １ protrusion or cavity of said CH3 domain is such that the ２ multispecific antigen-binding molecule according to claim 28, wherein the cavity or protrusion of said CH3 domain can each be disposed in the cavity or protrusion of said CH3 domain.

30. said CH3 １ domain and said CH3 ２ The multispecific antigen-binding molecule according to claim 29, wherein the domain and the domain associate at an interface between the protrusion and the cavity.

31. said CH2 １ domain and said CH2 ２ domains each comprise a protrusion or a cavity, and the protrusion or cavity of said CH2 １ domain is respectively capable of being disposed in the cavity or protrusion of said CH2 ２ domain, the multispecific antigen-binding molecule according to any one of claims 27 to 30.

32. said CH2 １ domain and said CH2 ２ The multispecific antigen-binding molecule according to claim 31, wherein the domain and the CH2 domain associate at an interface between the protrusion and the cavity.

33. The first antigen-binding domain comprises an anti-STEAP1 heavy chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 83 and an anti-STEAP1 light chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 82; the second antigen-binding domain comprises an anti-CD3 heavy chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 85 and an anti-CD3 light chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO:

84. The multispecific antigen-binding molecule according to any one of claims 22 and 27 to 32.

34. The first antigen-binding domain comprises an anti-STEAP1 heavy chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 85 and an anti-STEAP1 light chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 84; the second antigen-binding domain comprises an anti-CD3 heavy chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 83 and an anti-CD3 light chain constant region sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO:

82. The multispecific antigen-binding molecule according to any one of claims 22 and 27 to 32.

35. The multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 73, an anti-STEAP1 light chain comprising SEQ ID NO: 72, an anti-CD3 heavy chain comprising SEQ ID NO: 81, and an anti-CD3 light chain comprising SEQ ID NO:

80. The multispecific antigen-binding molecule according to any one of claims 22 and 27 to 32.

36. The multispecific antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 73, an anti-STEAP1 light chain comprising SEQ ID NO: 72, an anti-CD3 heavy chain comprising SEQ ID NO: 79, and an anti-CD3 light chain comprising SEQ ID NO:

78. The multispecific antigen-binding molecule according to any one of claims 22 and 27 to 32.

37. The antigen-binding molecule is a single-chain Fv (scFv), trispecific (Fab ３ ), bispecific (Fab ２ ), diabody ((V Ｌ -V Ｈ )) ２ or (V Ｈ -V Ｌ )) ２ ), tribody (trivalent), tetrabody (tetravalent), minibody ((scF Ｖ -C Ｈ )) ２ ), bispecific single-chain Fv (Bis-scFv), IgGdeltaCH2, scFv-Fc or (scFv) ２ -Fc, the multispecific antigen-binding molecule according to any one of claims 1 to 36.

38. The multispecific antigen-binding molecule according to any one of claims 1 to 37, wherein the multispecific antigen-binding molecule is a multispecific antibody, preferably a bispecific or trispecific antibody.

39. The multispecific antigen-binding molecule according to any one of claims 1 to 38, wherein the multispecific antigen-binding molecule further comprises a third antigen-binding domain that binds to a tumor-associated antigen.

40. The multispecific antigen-binding molecule according to claim 39, wherein the tumor-associated antigen is a receptor expressed on prostate cancer cells or Ewing sarcoma.

41. The multispecific antigen-binding molecule according to claim 39 or 40, wherein the tumor-associated antigen is prostate-specific membrane antigen (PSMA), STEAP2, prostate stem cell antigen (PSCA), epithelial cell adhesion molecule (EpCAM), prostate-specific antigen (PSA), prostate acid phosphatase (PAP), or HBA-71.

42. The multispecific antigen-binding molecule according to any one of claims 1 to 41, wherein the multispecific antigen-binding molecule binds to human STEAP1, cynomolgus STEAP1, or a combination thereof, and preferably, the multispecific antigen-binding molecule binds to human STEAP1 of SEQ ID NO:

65.

43. The multispecific antigen-binding molecule according to any one of claims 1 to 42, wherein the first antigen-binding domain binds to at least one residue selected from Ser101, His102, Gln103, and Lys281 of STEAP1, and the residue positions 101, 102, 103, and 281 correspond to the positions 101, 102, 103, and 281 shown in SEQ ID NO:

65.

44. The multispecific antigen-binding molecule according to any one of claims 1 to 43, wherein the first antigen-binding domain binds to Ser101, His102, Gln103, and Lys281 of STEAP1.

45. The multispecific antigen-binding molecule has a C of about 11, 11.5, 12, 12.6, 13, 13.5, 15, 18, 20, 23.4, 25, 27.9, 29.1, or 30 μg / mL ｍａｘ The multispecific antigen-binding molecule according to any one of claims 1 to 44, having the same.

46. The multispecific antigen-binding molecule has a C of about 11 μg / mL to about 30 μg / mL ｍａｘ The multispecific antigen-binding molecule according to any one of claims 1 to 44, which has such a property.

47. The multispecific antigen-binding molecule has a C of about 20 μg / mL to about 28 μg / mL ｍａｘ The multispecific antigen-binding molecule according to claim 46, which has such a property.

48. The multispecific antigen-binding molecule having a C of about 24 μg / mL ｍａｘ The multispecific antigen-binding molecule according to claim 47, which has

49. The multispecific antigen-binding molecule has an EC of about 0.6, 0.56, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.09, 0.05, or less ５０ The multispecific antigen-binding molecule according to any one of claims 1 to 48, having the same.

50. The multispecific antigen-binding molecule has an EC of from about 0.05 to about 0.8 ５０ The multispecific antigen-binding molecule according to any one of claims 1 to 48, having such an EC value.

51. said EC ５０ was determined in a cell killing assay at 72 hours using human CD8+ T cells and STEAP1-expressing LNCaP-X1.2 cells, and said EC ５０ is from about 0.05 to about 0.4, the multispecific antigen-binding molecule of claim 50.

52. Said EC ５０ The multispecific antigen-binding molecule according to claim 51, wherein said EC is about 0.08 or about 0.

3.

53. said EC ５０ is determined in a cell killing assay at 72 hours using human CD8+ T cells and STEAP1-expressing LNCaP X1.2KO3-13 cells, and said EC ５０ is from about 0.1 to about 0.8, the multispecific antigen-binding molecule of claim 50.

54. Said EC ５０ The multispecific antigen-binding molecule according to claim 53, wherein the value is about 0.1 or about 0.

7.

55. An antigen-binding molecule that binds to STEAP1, comprising a CDR-H1, CDR-H2, and CDR-H3 of a VH sequence selected from SEQ ID NO: 7, 17-25, 30-34, 38, and 68, an anti-STEAP1 heavy chain variable region (VH); and a CDR-L1, CDR-L2, and CDR-L3 of a VL sequence selected from SEQ ID NO: 8, 26-29, 39, and 69, an anti-STEAP1 light chain variable region (VL).

56. An antigen-binding molecule that binds to STEAP1, comprising an anti-STEAP1 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3; and an anti-STEAP1 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3; Here, CDR-H1 is Xaa １ Xaa ２ and includes YMA (SEQ ID NO: 35); Wherein, Xaa １ is Asp (D) or Asn (N); and Xaa ２ is His (H), Tyr (Y), or Phe (F); CDR-H2 is YIXaa ３ YDGXaa ４ Xaa ５ TXaa ６ comprises YGDSSVK (SEQ ID NO: 36); Wherein, Xaa ３ is Asp(D) or Ser(S); Xaa ４ is Gly (G), Asp (D) or Leu (L); Xaa ５ is Ser (S), Asp (D) or Asn (N); and Xaa ６ is Ser (S) or Tyr (Y); CDR-H3 is RSGXaa ７ YHVGYAMXaa ８ Xaa ９ (SEQ ID NO: 37); Wherein, Xaa ７ is Phe (F) or Tyr (Y); Xaa ８ is Asn (N) or Asp (D); and Xaa ９ is Ala (A) or Gly (G); CDR-L1 comprises the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprises the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprises the amino acid sequence of SEQ ID NO: 6, an antigen-binding molecule.

57. The antigen-binding molecule according to claim 55 or 56, wherein the CDR-H1 comprises the amino acid sequence of SEQ ID NO: 10, 1, or 9.

58. The antigen-binding molecule according to any one of claims 55-57, wherein the CDR-H2 comprises the amino acid sequence of SEQ ID NO: 2, 11, 12, or 13.

59. The antigen-binding molecule according to any one of claims 55-58, wherein the CDR-H3 comprises the amino acid sequence of SEQ ID NO: 16, 3, 14, or 15.

60. The antigen-binding molecule according to any one of claims 55-59, wherein the antigen-binding molecule is CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 16; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6, an antigen-binding molecule.

61. The antigen-binding molecule according to any one of claims 55-59, wherein the antigen-binding molecule is CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6, an antigen-binding molecule.

62. An antigen-binding molecule according to any one of claims 55 to 59, wherein the antigen-binding molecule comprises: CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 11; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO:

6.

63. An antigen-binding molecule according to any one of claims 55 to 59, wherein the antigen-binding molecule comprises: CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO:

6.

64. An antigen-binding molecule according to any one of claims 55 to 59, wherein the antigen-binding molecule comprises: CDR-H1 comprising the amino acid sequence of SEQ ID NO: 9; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 12; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 14; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO:

6.

65. An antigen-binding molecule according to any one of claims 55 to 59, wherein the antigen-binding molecule comprises: CDR-H1 comprising the amino acid sequence of SEQ ID NO: 10; CDR-H2 comprising the amino acid sequence of SEQ ID NO: 13; CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15; CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and CDR-L3 comprising the amino acid sequence of SEQ ID NO:

6.

66. The antigen-binding molecule according to any one of claims 55 to 65, wherein the antigen-binding molecule is a humanized antibody.

67. The antigen-binding molecule includes an IgG framework region and optionally an IgG １ framework region, and the antigen-binding molecule according to any one of claims 55 to 66.

68. An antigen-binding molecule according to any one of claims 55 to 67, comprising a VH variable region of an anti-STEAP1 heavy chain having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 7, 17-25, 30-34, 38 or 68.

69. An antigen-binding molecule according to any one of claims 55 to 68, comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 8, 26-29, 39 or 69.

70. An antigen-binding molecule according to any one of claims 55 to 69, comprising an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 68, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO:

69.

71. An antigen-binding molecule according to any one of claims 55 to 69, comprising an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 34, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO:

27.

72. An antigen-binding molecule according to any one of claims 55 to 69, comprising an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 30, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO:

27.

73. An antigen-binding molecule according to any one of claims 55 to 69, comprising an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 31, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO:

27.

74. An antigen-binding molecule according to any one of claims 55 to 69, comprising an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO: 32, and an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity to SEQ ID NO:

27. **Claim 75** An antigen-binding molecule according to any one of claims 55 to 69, comprising a VH region of an anti-STEAP1 heavy chain variable region having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 33, and a VL region of an anti-STEAP1 light chain variable region having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

27. **Claim 76** The antigen-binding molecule according to any one of claims 55 to 75, wherein the antigen-binding molecule comprises an anti-STEAP1 heavy chain constant region sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 83 and an anti-STEAP1 light chain constant region sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 82; or the antigen-binding molecule comprises an anti-STEAP1 heavy chain constant region sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 85 and an anti-STEAP1 light chain constant region sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

84. **Claim 77** The antigen-binding molecule according to claim 76, wherein the antigen-binding molecule comprises an anti-STEAP1 heavy chain comprising SEQ ID NO: 73 and an anti-STEAP1 light chain comprising SEQ ID NO:

72. **Claim 78** The antigen-binding molecule according to any one of claims 55 to 77, wherein the antigen-binding molecule is a full-length antibody or a fragment thereof. **Claim 79** The antigen-binding molecule is Fab, Fab', F(ab') ２ , Fv, Fd, single-chain Fv (scFv), trispecific (Fab ３ ), bispecific (Fab ２ ), diabody ((V Ｌ -V Ｈ ), ２ or (V Ｈ -V Ｌ ), ２ ), tribody (trivalent), tetrabody (tetravalent), minibody ((scF Ｖ -C Ｈ ), ２ ), bispecific single-chain Fv (Bis-scFv), IgGdeltaCH2, scFv-Fc or (scFv) ２ -Fc, and is the antigen-binding molecule according to any one of claims 55 to 78. **Claim 80** The antigen-binding molecule according to any one of claims 55 to 79, wherein the antigen-binding molecule further comprises an antigen-binding domain that binds to a T cell receptor. **Claim 81** The antigen-binding molecule according to any one of claims 55 to 80, wherein the antigen-binding molecule is a multispecific antibody, preferably the antigen-binding molecule is a bispecific antibody or a trispecific antibody. **Claim 82** The antigen-binding molecule according to claim 80 or 81, wherein the T cell receptor is cluster of differentiation 3 (CD3). **Claim 83** The antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region (VH) containing CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light chain variable region (VL) containing CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the amino acid sequences of SEQ ID NOs: 48 to 53. The antigen-binding molecule according to claim 82.

84. The antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region containing a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 54, and an anti-CD3 light chain variable region containing a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

55. The antigen-binding molecule according to claim 83.

85. The antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region (VH) containing CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light chain variable region (VL) containing CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the amino acid sequences of SEQ ID NOs: 40 to 45. The antigen-binding molecule according to claim 82.

86. The antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region containing a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 46, and an anti-CD3 light chain variable region containing a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

47. The antigen-binding molecule according to claim 83.

87. The antigen-binding molecule comprises an anti-CD3 heavy chain containing SEQ ID NO: 79 and an anti-CD3 light chain containing SEQ ID NO:

78. The antigen-binding molecule according to claim 82.

88. The antigen-binding molecule comprises an anti-CD3 heavy chain containing SEQ ID NO: 81 and an anti-CD3 light chain containing SEQ ID NO:

80. The antigen-binding molecule according to claim 82.

89. The antigen-binding molecule further comprises an additional antigen-binding domain that binds to a tumor-associated antigen. The antigen-binding molecule according to any one of claims 55 to 88.

90. The antigen-binding molecule according to claim 89, wherein the tumor-associated antigen is a receptor expressed on prostate cancer cells or Ewing's sarcoma.

91. The antigen-binding molecule according to claim 89 or 90, wherein the tumor-associated antigen is prostate-specific membrane antigen (PSMA), STEAP2, prostate stem cell antigen (PSCA), epithelial cell adhesion molecule (EpCAM), prostate-specific antigen (PSA), prostate acid phosphatase (PAP), or HBA-71.

92. The antigen-binding molecule according to any one of claims 55 to 91, wherein the antigen-binding molecule binds to human STEAP1, cynomolgus STEAP1, or a combination thereof, and preferably, the antigen-binding molecule binds to human STEAP1 of SEQ ID NO:

65.

93. The antigen-binding molecule according to any one of claims 55 to 92, wherein the antigen-binding molecule binds to at least one residue selected from Ser101, His102, Gln103, and Lys281 of STEAP1, and the residue positions 101, 102, 103, and 281 correspond to the positions 101, 102, 103, and 281 shown in SEQ ID NO:

65.

94. The antigen-binding molecule according to any one of claims 55 to 93, wherein the antigen-binding molecule binds to Ser101, His102, Gln103, and Lys281 of SEQ ID NO:

65.

95. An antibody comprising a first antigen-binding domain that binds to human STEAP1 at one or more residues selected from Ser101, His102, Gln103, and Lys281, wherein the residue positions 101, 102, 103, and 281 correspond to the positions 101, 102, 103, and 281 shown in SEQ ID NO:

65.

96. The antibody according to claim 95, wherein the first antigen-binding domain binds to Ser101, His102, Gln103, and Lys281 of SEQ ID NO:

65.

97. The antibody according to claim 95 or 96, wherein the heavy chain variable region of the first antigen-binding domain forms a hydrogen bond with at least one residue selected from Ser101, His102, Gln103, and Lys281.

98. The Leu56, Ser73, and Asn74 of the heavy chain variable region of the first antigen-binding domain form hydrogen bonds with Ser101, His102, Gln103, and Lys281 of STEAP1, and the residue positions of the heavy chain variable region correspond to positions 56, 73, and 74 shown in SEQ ID NO:

18. The antibody according to any one of claims 95 to 97.

99. The first antigen-binding domain comprises a CDR-H1, CDR-H2, and CDR-H3 of a VH sequence selected from SEQ ID NOs: 7, 17 to 25, 30 to 34, 38, and 68, an anti-STEAP1 heavy chain variable region (VH); and a CDR-L1, CDR-L2, and CDR-L3 of a VL sequence selected from SEQ ID NOs: 8, 26 to 29, 39, and 69, an anti-STEAP1 light chain variable region (VL) of three CDRs. The antibody according to any one of claims 95 to 98.

100. The first antigen-binding domain comprises an anti-STEAP1 heavy chain variable region comprising a VH sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NOs: 7, 17 to 25, 30 to 34, 38, or 68. The antibody according to any one of claims 95 to 99.

101. The first antigen-binding domain comprises an anti-STEAP1 light chain variable region comprising a VL sequence having at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NOs: 8, 26 to 29, 39, or 69. The antibody according to any one of claims 95 to 100.

102. The antibody further comprises a second antigen-binding domain that binds to a T cell receptor. The antibody according to any one of claims 95 to 101.

103. The T cell receptor is cluster of differentiation 3 (CD3). The antibody according to claim 102.

104. The second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3. The CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the amino acid sequences of SEQ ID NOs: 48 to 53. The antibody according to claim 103.

105. The antibody according to claim 104, wherein the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region having a VH sequence with at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 54, and an anti-CD3 light chain variable region having a VL sequence with at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

55.

106. The antibody according to claim 103, wherein the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region (VH) comprising CDR-H1, CDR-H2, and CDR-H3, and an anti-CD3 light chain variable region (VL) comprising CDR-L1, CDR-L2, and CDR-L3, and the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 each comprise the amino acid sequences of SEQ ID NOs: 40 to 45.

107. The antibody according to claim 106, wherein the second antigen-binding domain that binds to CD3 comprises an anti-CD3 heavy chain variable region having a VH sequence with at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 46, and an anti-CD3 light chain variable region having a VL sequence with at least 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:

47.

108. The antibody according to any one of claims 95 to 107, wherein the multispecific antigen-binding molecule further comprises a third antigen-binding domain that binds to a tumor-associated antigen.

109. The antibody according to claim 108, wherein the tumor-associated antigen is a receptor expressed on prostate cancer cells.

110. The antibody according to claim 108 or 109, wherein the tumor-associated antigen is prostate-specific membrane antigen (PSMA), STEAP2, prostate stem cell antigen (PSCA), epithelial cell adhesion molecule (EpCAM), prostate-specific antigen (PSA), or prostate acid phosphatase (PAP).

111. One or more isolated nucleic acids encoding the multispecific antigen-binding molecule according to any one of claims 1 to 54, the antigen-binding molecule according to any one of claims 55 to 94, or the antibody according to any one of claims 95 to 110, individually or together.

112. One or more vectors comprising the one or more isolated nucleic acids according to claim 111, individually or together.

113. One or more host cells comprising, individually or together, one or more isolated nucleic acids according to claim 111 or one or more vectors according to claim 112.

114. One or more host cells according to claim 113, wherein the host cell is a mammalian cell.

115. One or more host cells according to claim 114, wherein the mammalian cell is a Chinese hamster ovary (CHO) cell.

116. One or more host cells according to claim 113, wherein the host cell is an insect cell.

117. One or more host cells according to claim 113, wherein the host cell is a prokaryotic cell.

118. A method for producing a multispecific antigen-binding molecule according to any one of claims 1 to 54, an antigen-binding molecule according to any one of claims 55 to 94, or an antibody according to any one of claims 95 to 110, comprising culturing one or more host cells according to any one of claims 113 to 117 in a culture medium.

119. The method according to claim 118, further comprising harvesting from the one or more host cells or the culture medium a multispecific antigen-binding molecule according to any one of claims 1 to 54, an antigen-binding molecule according to any one of claims 55 to 94, or an antibody according to any one of claims 95 to 110.

120. A pharmaceutical composition comprising a multispecific antigen-binding molecule according to any one of claims 1 to 54, an antigen-binding molecule according to any one of claims 55 to 94, or an antibody according to any one of claims 95 to 110.

121. The pharmaceutical composition according to claim 120, further comprising a pharmaceutically acceptable carrier, excipient, or diluent.

122. The pharmaceutical composition according to claim 120 or 121 for use as a medicament.

123. The pharmaceutical composition according to claim 120 or 121 for use in the treatment or delay of progression of STEAP1-expressing cancer.

124. The pharmaceutical composition according to claim 120 or 121 for use in the treatment or delay of progression of prostate cancer or Ewing sarcoma.

125. The multispecific antigen-binding molecule according to any one of claims 1 to 54, the antigen-binding molecule according to any one of claims 55 to 94, or the antibody according to any one of claims 95 to 110 for use in treating or delaying the progression of STEAP1-expressing cancer in a subject in need thereof.

126. The multispecific antigen-binding molecule according to any one of claims 1 to 54, the antigen-binding molecule according to any one of claims 55 to 94, or the antibody according to any one of claims 95 to 110 for use in inhibiting or reducing the growth of STEAP1-expressing cancer cells.

127. The multispecific antigen-binding molecule for use according to claim 125 or 126, the antigen-binding molecule for such use, or the antibody for such use, wherein the STEAP1-expressing cancer is a solid tumor.

128. The multispecific antigen-binding molecule for use according to any one of claims 125 to 127, the antigen-binding molecule for such use, or the antibody for such use, wherein the STEAP1-expressing cancer is prostate cancer or Ewing sarcoma.

129. The multispecific antigen-binding molecule for use according to any one of claims 125 to 128, the antigen-binding molecule for such use, or the antibody for such use, which is used in combination with an additional therapeutic agent or an additional treatment regimen.

130. The multispecific antigen-binding molecule for use according to claim 129, the antigen-binding molecule for such use, or the antibody for such use, wherein the additional therapeutic agent comprises a chemotherapeutic agent, an immunotherapeutic agent, a targeted therapy, radiotherapy, or a combination thereof.

131. The multispecific antigen-binding molecule for use according to claim 129 or 130, the antigen-binding molecule for such use, or the antibody for such use, wherein the additional therapeutic agent comprises a first-line, second-line, or third-line therapy.

132. The multispecific antigen-binding molecule for use according to claim 129, the antigen-binding molecule for such use, or the antibody for such use, wherein the additional treatment regimen comprises surgery.

133. The multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody, and the additional therapeutic agent are administered simultaneously, a multispecific antigen-binding molecule for use according to any one of claims 129 to 131, an antigen-binding molecule for such use, or an antibody for such use.

134. The multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody, and the additional therapeutic agent are administered sequentially, a multispecific antigen-binding molecule for use according to any one of claims 129 to 131, an antigen-binding molecule for such use, or an antibody for such use.

135. The multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered first before the additional therapeutic agent is administered, a multispecific antigen-binding molecule for use according to any one of claims 129 to 131, an antigen-binding molecule for such use, or an antibody for such use.

136. The multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered after the additional therapeutic agent is administered, a multispecific antigen-binding molecule for use according to any one of claims 129 to 131, an antigen-binding molecule for such use, or an antibody for such use.

137. The multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered systemically, a multispecific antigen-binding molecule for use according to any one of claims 125 to 136, an antigen-binding molecule for such use, or an antibody for such use.

138. The multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered locally, a multispecific antigen-binding molecule for use according to any one of claims 125 to 136, an antigen-binding molecule for such use, or an antibody for such use.

139. The multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered parenterally, a multispecific antigen-binding molecule for use according to any one of claims 125 to 136, an antigen-binding molecule for such use, or an antibody for such use.

140. The multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered intravenously or subcutaneously, a multispecific antigen-binding molecule for use according to any one of claims 125 to 136, an antigen-binding molecule for such use, or an antibody for such use.

141. A multispecific antigen-binding molecule for use according to any one of claims 125 to 136, an antigen-binding molecule for such use, or an antibody for such use, wherein the subject is a human.

142. Use of a multispecific antigen-binding molecule according to any one of claims 1 to 54, an antigen-binding molecule according to any one of claims 55 to 94, or an antibody according to any one of claims 95 to 110, in the manufacture of a medicament for treating or delaying the progression of STEAP1-expressing cancer, optionally for treating or delaying the progression of prostate cancer or Ewing sarcoma, in a subject in need of treatment or delay of progression of STEAP1-expressing cancer.

143. Use of a multispecific antigen-binding molecule according to any one of claims 1 to 54, an antigen-binding molecule according to any one of claims 55 to 94, or an antibody according to any one of claims 95 to 110, in the manufacture of a medicament 16, optionally for the manufacture of prostate cancer cells or Ewing sarcoma cells.

144. A method for treating or delaying the progression of STEAP1-expressing cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of a multispecific antigen-binding molecule according to any one of claims 1 to 54, an antigen-binding molecule according to any one of claims 55 to 94, or an antibody according to any one of claims 95 to 110.

145. The method according to claim 144, wherein the STEAP1-expressing cancer is a solid tumor.

146. The method according to claim 144 or 145, wherein the STEAP1-expressing cancer is prostate cancer or Ewing sarcoma.

147. The method according to any one of claims 144 to 146, further comprising administering to the subject an additional therapeutic agent or an additional treatment regimen.

148. The method according to claim 147, wherein the additional therapeutic agent comprises a chemotherapeutic agent, an immunotherapeutic agent, a targeted therapy, radiation therapy, or a combination thereof.

149. The method according to claim 148, wherein the additional therapeutic agent comprises a first-line, second-line, or third-line therapy.

150. The method according to claim 148, wherein the additional treatment regimen comprises surgery.

151. The method according to any one of claims 144 to 150, wherein the multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody and the additional therapeutic agent are administered simultaneously.

152. The method according to any one of claims 144 to 150, wherein the multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody and the additional therapeutic agent are administered continuously.

153. The method according to claim 152, wherein the multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered first before administering the additional therapeutic agent.

154. The method according to claim 152, wherein the multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered after administering the additional therapeutic agent.

155. The method according to any one of claims 144 to 154, wherein the multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered systemically.

156. The method according to any one of claims 144 to 154, wherein the multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered locally.

157. The method according to any one of claims 144 to 156, wherein the multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered parenterally.

158. The method according to any one of claims 144 to 157, wherein the multispecific antigen-binding molecule, the antigen-binding molecule, or the antibody is administered intravenously or subcutaneously.

159. The method according to any one of claims 144 to 158, wherein the subject is a human.

160. A method of inhibiting or reducing the proliferation of STEAP1-expressing cells, the method comprising contacting the cells with a multispecific antigen-binding molecule according to any one of claims 1 to 54, an antigen-binding molecule according to any one of claims 55 to 94, or an antibody according to any one of claims 95 to 110 for a time sufficient to inhibit the proliferation of the cells.

161. The method according to claim 160, wherein the cells are prostate cancer cells or Ewing sarcoma cells.

162. The method according to claim 160 or 161, wherein the method is an in vivo method.

163. The method according to claim 160 or 161, wherein the method is an in vitro or ex vivo method.

164. A kit comprising the multispecific antigen-binding molecule according to any one of claims 1 to 54, the antigen-binding molecule according to any one of claims 55 to 94, or the antibody according to any one of claims 95 to 110, the one or more isolated nucleic acids according to claim 111, the one or more vectors according to claim 112, the one or more host cells according to any one of claims 113 to 117, or the pharmaceutical composition according to any one of claims 120 to 124, optionally comprising a set of instructions.

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