B7h3 / epha2 antibodies and methods of use

Abstract

Provided herein are multivalent, multi-specific antibodies that specifically bind B7H3 and EphA2; wherein each paratope specifically binds B7H3 or EphA2, and the paratopes, collectively, specifically bind both B7H3 and EphA2. In certain embodiments, the antibodies are bivalent, trivalent or tetravalent. Also provided are immunoconjugates, which may be antibody-drug conjugates. Further provided are methods of using these antibodies for killing or detecting malignant cells and for treating diseases, including cancer.

Description

Docket No.: AARV-020-PCTB7H3 / EphA2 Antibodies and Methods of UseSTATEMENT AS TO FEDERALLY SPONSORED RESEARCH

[0001] None.REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of the priority date of U. S. Provisional application 63 / 764,538, filed February 27, 2025, the contents of which are incorporated herein by reference.SEQUENCE LISTING

[0003] None.BACKGROUND

[0004] Antibody-drug conjugates (ADCs) represent a significant advance in cancer therapy. ADCs incorporate the specificity of monoclonal antibodies with the potency of cytotoxic drugs. By targeting cancer cells with high precision, ADCs reduce harm to healthy tissues. In an ADC, the monoclonal antibody is designed to bind to a specific antigen that is expressed on the surface of cancer cells. Once bound, the ADC is internalized into the cancer cell, where the cytotoxic agent is released to induce cell death. This targeted delivery allows for the use of highly potent drugs that might be too toxic if delivered systemically. ADCs have shown promise in treating various cancers, including solid tumors and hematological malignancies. These biologies represent a personalized and targeted cancer therapy.BRIEF DESCRIPTION OF THE DRAWINGS

[0005] The accompanying drawings, which are incorporated herein and form a part of the specification, illustrate exemplary embodiments and, together with the description, further serve to enable a person skilled in the pertinent art to make and use these embodiments and others that will be apparent to those skilled in the art. The invention will be more particularly described in conjunction with the following drawings wherein:

[0006] FIG. 1 shows four different formats for multi-specific (e.g., bi-specific) tetravalent symmetric antibodies. Symmetry herein refers to “east-west” symmetry. If east-west epitope binding of paratopes are mirror images, the antibody is symmetric, and if not, the antibody is asymmetric. Fig. 1A: Platform 2 or a Diabody-Fc-Fab format for a symmetric antibody in which the paratopes binding Epitope 1 (paratopes 1 and 2) are in the NW / NE positions, and theDocket No.: AARV-020-PCT paratopes binding Epitope 2 (paratopes 3 and 4) are in the SW / SE positions. Fig. 1B: Platform 4 or a Fab-Diabody-Fc format for a symmetric antibody in which the paratopes binding epitope 1 (paratopes 1 and 2) are in the NW / NE positions, and the paratopes binding epitope 2 (paratopes 3 and 4) are in the SW / SE positions. Fig. 1C: Platform 1 or a Fab-Fc-Fab format for a symmetric antibody in which the paratopes binding Epitope 1 (paratopes 1 and 2) are in the NW / NE positions, and the paratopes binding Epitope 2 (paratopes 3 and 4) are in the SW / SE positions. Fig. 1D: Platform 3 or a Fab-Fab-Fc format for a symmetric antibody in which the paratopes binding Epitope 1 (paratope 1 and paratope 2) are in the NW / NE positions, and the paratopes binding Epitope 2 (paratopes 3 and 4) are in the SW / SE positions.

[0007] FIG. 2 shows four configurations for tetravalent multi-specific (e.g., bi-specific) antibodies in the Platform 2 or Diabody-Fc-Fab format. Fig. 2A. A symmetric antibody where Paratopes 1 and 2 (NW and NE, respectively) bind to Epitope 1; and Paratopes 3 and 4 (SW and SE, respectively) bind to Epitope 2. Fig. 2B. A symmetric antibody where Paratopes 1 and 2 (NW and NE, respectively) bind to Epitope 2; and Paratopes 3 and 4 (SW and SE, respectively) bind to Epitope 1. Fig. 2C. An asymmetric antibody where Paratopes 1 and 4 (NW and SE, respectively) bind to Epitope 1; and Paratopes 2 and 3 (NE and SW, respectively) bind to Epitope 2. Fig. 2D. An asymmetric antibody where Paratopes 1 and 3 (NW and SW, respectively) bind to Epitope 1; and Paratopes 2 and 4 (NE and SE, respectively) bind to Epitope 2.

[0008] FIG. 3 shows four configurations for tetravalent multi-specific (e.g., bi-specific) antibodies in the Platform 4 or Fab-Diabody-Fc format. Fig. 3A. A symmetric antibody where Paratopes 1 and 2 (NW and NE, respectively) bind to Epitope 1; and Paratopes 3 and 4 (SW and SE, respectively) bind to Epitope 2. Fig. 3B. A symmetric antibody where Paratopes 1 and 2 (NW and NE, respectively) bind to Epitope 2; and Paratopes 3 and 4 (SW and SE, respectively) bind to Epitope 1. Fig. 3C. An asymmetric antibody where Paratopes 1 and 4 (NW and SE, respectively) bind to Epitope 1; and Paratopes 2 and 3 (NE and SW, respectively) bind to Epitope 2. Fig. 3D. An asymmetric antibody where Paratopes 1 and 3 (NW and SW, respectively) bind to Epitope 1; and Paratopes 2 and 4 (NE and SE, respectively) bind to Epitope 2.

[0009] FIG. 4 shows eight different formats for multi-specific (e.g., bi-specific) tetravalent antibodies. The positions of the paratopes directed to a first target (say, B7H3) and a second target (say, EphA2) are exemplary. The antibodies can be engineered, e.g., with common light chain variable regions, such that the paratopes directed to specific epitopes can be placed in any arrangement. All these molecules have east-west symmetry, except for Fig. 4B and FIG. 4H. Fig. 4A: Fab-Fc-scFv format. Fig. 4B: Fab / scFv-Fc-Fab / scFv format. Fig. 4C: Diabody-Fc-Diabody format. Fig. 4D: Diabody-Fc-scFv format. Fig. 4E: scFv-Fc-Diabody format. Fig. 4F: scFv-Fc-scFv format. Fig. 4G: Fab-Fc-Diabody format. Fig. 4H: scFv / Fab-Fc-Fab / scFv format.Docket No.: AARV-020-PCT Note that if east-west epitope binding of paratopes are mirror images, the antibody is symmetric, and if not, the antibody is asymmetric.

[0010] FIG. 5 shows three formats for asymmetric bivalent multi-specific (e.g., bispecific) antibodies. Symmetry herein refers to “east-west” symmetry. If east-west epitope binding of paratopes are mirror images, the antibody is symmetric, and if not, the antibody is asymmetric. Fig. 5A: An asymmetric (Fab)2-Fc (IgG) antibody. Fig. 5B: An asymmetric Fab-scFv-Fc antibody. Fig. 5C: An asymmetric diabody-Fc antibody.

[0011] FIGs. 6A-6B show two formats for a trivalent antibody in an asymmetric Fab1 -Diabody-Fc antibody. Asymmetry herein refers to “east-west” asymmetry. 6A shows an Fab attached to an Fc region comprising a hole, while 6B shows an Fab attached to an Fc region comprising a knob. The arrangement of a Fab comprising a Epitope 1 binder ( / .e., a Epitope 1 paratope) or a Epitope 2 binder ( / .e., a Epitope 2 paratope), connected to a diabody region comprising Epitope 1 and Epitope 2 paratopes is exemplary; the paratopes can be placed in any arrangement.

[0012] FIG. 7 shows bivalent mono-specific antibodies with engineered cysteine residues binding B7H3-E1 or EphA2-E1. Fig.7A: antibody binding EphA2-E1 (AB2001); Fig. 7B: antibody binding EphA2-E2 (AB2002); Fig. 7C: antibody binding B7H3-E1 (AB2003); Fig.7D: antibody binding B7H3-E2 (AB2004). Asterix at variable region of heavy or light chain indicates binding to E2 epitope of the target antigen. All antibodies described here may have engineered cysteine residues in the heavy and light chains at sequences VTVSSCSTKGP (SEQ. I D: 1) and GLSSPCTKSFN (SEQ. I D:2) respectively.

[0013] FIG. 8 shows asymmetric bivalent bispecific antibodies in the bis-diabody-Fc format. Fig. 8A: antibody binding B7H3-E1 and EphA2-E1 (AB2024); Fig. 8B: antibody binding B7H3-E1 and EphA2-E2 (AB2032). Asterix at variable region of heavy or light chain indicates binding to E2 epitope of the target antigen. These antibodies may have engineered cysteine residues in heavy chain sequences LLGGPCVFLFP (SEQ. ID NO:3) and CVVVDCSHEDP (SEQ. ID NO:4).

[0014] FIG. 9 shows symmetric tetravalent multi-specific antibodies binding both B7H3 and EphA2 and having a diabody-Fc-Fab (MLITTA2™) format. Fig. 9A: antibodies binding B7H3-E1 and EphA2-E1 without and with engineered cysteine residues (AB2006 and AB2017, respectively); Fig. 9B: antibodies binding B7H3-E1 and EphA2-E2 without and with engineered cysteine residues (AB2007 and AB2028, respectively); Fig. 9C: antibody binding B7H3-E2 and EphA2-E2 without and with engineered cysteine residues (AB2008 and AB2034, respectively);Fig. 9D: antibody binding B7H3-E2 and EphA2-E1 without engineered cysteine residues (AB2009); Fig. 9E: antibodies binding EphA2-E2 and B7H3-E2, without and with engineered cysteine residues (AB2010 and AB2033, respectively); Fig. 9F: antibodies binding EphA2-E2Docket No.: AARV-020-PCT and B7H3-E1, without and with engineered cysteine residues (AB2012 and AB2029, respectively); Fig. 9G: antibody binding EphA2-E1 and B7H3-E2, without engineered cysteine residues (AB2013); Fig. 9H: antibodies binding EphA2-E1 and B7H3-E1, without and with engineered cysteine residues (AB2015 and AB2018, respectively). Fig. 9I: antibody binding EphA2-E2b and B7H3-E1 with engineered cysteine residues and without LALA-PS (AB2027) or with l_AI_A-PS motif (AB2041). EphA2b means that the heavy chain CDRs have the sequences of AB2002 and the light chain CDRs have the sequence of AB2001. Asterix at variable region of heavy or light chain indicates binding to E2 epitope of the target antigen. The antibodies described here may have engineered cysteine residues in the heavy and light chains at sequences VTVSSCSTKGP (SEQ. I D: 1 ) and GLSSPCTKSFN (SEQ. I D:2) respectively. Antibodies with l-ALA-PS motif consists of the following substitutions in Fc domain of the heavy chain at L234A and L235A (CPAPEAAGGPSV; SEQ. ID:94) combined with P331S (KALPASIEKTIS; SEQ. ID:95).

[0015] FIG. 10 shows symmetric tetravalent multi-specific antibodies binding two epitopes of either B7H3 or EphA2 and having a diabody-Fc-Fab (MLITTA2™) format. Fig. 10A: antibody binding EphA2-E2 and EphA2-E1, without engineered cysteine residues (AB2011); Fig. 10B: antibody binding EphA2-E1 and EphA2-E2, without engineered cysteine residues (AB2016); Fig. 10C: antibody binding B7H3-E1 and B7H3-E2, with engineered cysteine residues (AB2023). Asterix at variable region of heavy or light chain indicates binding to E2 epitope of the target antigen. The antibody with engineered cysteine residues described here may have engineered cysteine residues in the heavy and light chains at sequences VTVSSCSTKGP (SEQ. I D: 1) and GLSSPCTKSFN (SEQ. I D:2) respectively.

[0016] FIG. 11 shows asymmetric tetravalent multi-specific antibodies with engineered cysteine residues binding both B7H3 and EphA2 and having a diabody-Fc-Fab (MUTTA2™) format. Fig. 11A: antibody binding EphA2-E1, B7H3-E1, and B7H3-E2 (AB2021);Fig. 11B: antibody binding EphA2-E1, EphA2-E2, B7H3-E1 and B7H3-E2 (AB2022). Asterix at variable region of heavy or light chain indicates binding to E2 epitope of the target antigen. The antibodies described here may have engineered cysteine residues in the heavy and light chains at sequences VTVSSCSTKGP (SEQ. I D: 1) and GLSSPCTKSFN (SEQ. I D:2) respectively.

[0017] FIG. 12 shows symmetric tetravalent multi-specific antibodies with engineered cysteine residues binding both B7H3 and EphA2 and having a Fab-diabody-Fc (MUTTA4™) format. Figs. 12A-B: antibodies binding B7H3-E1 and EphA2-E1 (AB2019 and AB2020); Fig. 12C-D: antibodies binding B7H3-E1 and EphA2-E2 (AB2025 and AB2026), and with the l_AI_A-PS motif (AB2030 and AB2031); Fig. 12E-F: antibodies binding B7H3-E2 and EphA2-E2 (AB2035 and AB2036), and with the LALA-PS motif (AB2037 and AB2038). 12G: antibody binding B7H3-E1 and EphA2-E2b (AB2039) and with LALA-PS motif (AB2040).EphA2b means that the heavy chain CDRs have the sequences of AB2002 and the light chainDocket No.: AARV-020-PCT CDRs have the sequence of AB2001. Asterix at variable region of heavy or light chain indicates binding to E2 epitope of the target antigen. The antibodies described here may have engineered cysteine residues in the heavy and light chains at sequences VTVSSCSTKGP (SEQ. I D: 1) and GLSSPCTKSFN (SEQ. ID:2) respectively. Antibodies with l_AI_A-PS motif consists of the following substitutions in Fc domain of the heavy chain at L234A and L235A (CP PEAAGGPSV,- SEQ. ID:94) combined with P331S (KALP SIEKTIS; SEQ. ID:95).

[0018] FIG. 13 shows scatter plots depicting co-expression of B7H3 (CD276) and EphA2 RNA (analyzed using publicly available GEPIA2 tool, Gene Expression Profiling Interactive Analysis, Zhang Lab, Peking University). Fig. 13A: lung adenocarcinoma (LUAD); Fig. 13B: ovarian cancer (OV).

[0019] FIG. 14 shows R values (correlation coefficients) for co-expression of B7H3 and EphA2 RNA in various cancers. COAD - colon adenocarcinoma; GBM -glioblastoma multiforme, KIRC / KIRP - kidney renal clear cell carcinoma / kidney renal papillary cell carcinoma, LIHC - liver hepatocellular carcinoma, LUAD - lung adenocarcinoma, MESO -mesothelioma, OV - ovarian serous cystadenocarcinoma, PAAD - pancreatic adenocarcinoma, READ - rectum adenocarcinoma, SARC - sarcoma, STAD - stomach adenocarcinoma, TGCT - testicular germ cell tumors, THCA - thyroid carcinoma, THYM - thymoma, UCEC - uterine corpus endometrial carcinoma, UCS - uterine carcinosarcoma, UVM - uveal melanoma, ACC -adrenocortical carcinoma, BLCA - bladder urothelial carcinoma, CESC - cervical squamous cell carcinoma and endocervical adenocarcinoma, ESCA - esophageal carcinoma, HNSC - head and neck squamous cell carcinoma, LUSC - lung squamous cell carcinoma, PRAD - prostate adenocarcinoma, SKCM - skin cutaneous melanoma.

[0020] FIG. 15 shows ECso values of bivalent mono-specific antibodies and IC50 of vc-MMAE ADCs of these antibodies binding B7H3 (AB2003 and AB2004) or EphA2 (AB2001 and AB2002) in BxPC3, JIMT 1, and / or OVCAR3 cell lines. NA - Not Assayed.

[0021] FIG. 16 shows cytotoxicity curves and IC50 values of tetravalent multispecific ADCs in MUTTA2™ format with vcMMAE linker-payload in (wild type) JIMT1 cells. Fig.16A shows cytotoxicity of vc-MMAE ADCs of AB2001, AB2003, AB2004, AB2013, and AB2015;Fig. 16B shows IC50 values of vc-MMAE ADCs of AB2001, AB2003, AB2004, AB2006, AB2009, AB2013, and AB2015; Fig. 16C shows cytotoxicity of vc-MMAE ADCs of AB2001, AB2011, and AB2016; Fig. 16D shows IC50 values of vc-MMAE ADCs of AB2001, AB2002, AB2011, and AB2016; Fig. 16E: shows IC50 values of vc-MMAE ADCs of AB2002, AB2003, AB2004, AB2007, AB2008, AB2010, and AB2012; Fig. 16F shows cytotoxicity of vc-MMAE ADCs of AB2002, AB2003, AB2025, AB2026, AB2027, and AB2028; Fig. 16G shows IC50 values of vc-MMAE ADCs of AB2002, AB2003, AB2025, AB2026, AB2027, and AB2028.Docket No.: AARV-020-PCT

[0022] FIG. 17 shows cytotoxicity curves and IC50 values of tetravalent multispecific ADCs with vcMMAE linker-payload in JIMT1 cells with knockdown (KD) of B7H3 or EphA2. Fig. 17A shows cytotoxicity of vc-MMAE ADCs of AB2002, AB2003, AB2025, AB2026, AB2027, and AB2028 in B7H3 KD cells; Fig. 17B shows IC50 values of vc-MMAE ADCs of AB2002, AB2003, AB2025, AB2026, AB2027, and AB2028 in B7H3 KD cells; Fig. 17C shows cytotoxicity of vc-MMAE ADCs of AB2002, AB2003, AB2025, AB2026, AB2027, and AB2028 in EphA2 KD cells; Fig. 17D shows IC50 values of vc-MMAE ADCs of AB2002, AB2003, AB2025, AB2026, AB2027, and AB2028 in EphA2 KD cells.

[0023] FIG. 18 shows cytotoxicity curves and IC50 values of ADCs with vcMMAE linker-payload conjugated to AB2002, AB2003, AB2025, AB2026, AB2027, and AB2028 in Fig.s 18A, 18B: a mixture (50:50) of JIMT1-B7H3-KD cells (with knockdown of B7H3 gene) and JIMT1-EphA2-KD cells (with knockdown of EphA2 gene); Fig.s 18C, 18D: a mixture (40:40:20) of JIMT1-B7H3-KD cells, JIMT1-EphA2-KD, and wild type JIMT1 cells. Fig.s 18A, 18C:cytotoxicity curves; Fig.s 18B, 18D: IC50 values.

[0024] FIG. 19 shows cytotoxicity curves and IC50 values of ADCs with vcMMAE linker-payload conjugated to AB2002, AB2003, AB2025, AB2026, AB2027, and AB2028 in OVCAR3 cells. Fig. 19A: cytotoxicity curves; Fig. 19B: IC50 values.

[0025] FIG. 20 shows cytotoxicity curves and IC50 values of ADCs with vcMMAE linker-payload conjugated to AB2002, AB2003, AB2025, AB2026, AB2027, and AB2028 in BxPC3 cells. Fig. 20A: cytotoxicity curves; Fig. 20B: IC50 values.

[0026] FIG. 21 shows cytotoxicity curves and IC50 values of ADCs with vcMMAE linker-payload conjugated to AB2002, AB2003, AB2025, AB2027, and AB2029 in H358 cells.Fig. 21 A: cytotoxicity curves; Fig. 21 B: IC50 values.

[0027] FIG. 22 shows cytotoxicity curves and IC50 values of ADCs with AV-DL112B linker-payload conjugated to AB2002, AB2003, mixture of AB2002 and AB2003, and AB2027 in OVCAR3 cells. Fig. 22A: cytotoxicity curves; Fig. 22B: IC50 values.

[0028] FIG. 23 shows cytotoxicity curves and IC50 values of ADCs with AV-DL055B linker-payload conjugated to AB2002, AB2003, AB2025, AB2027, AB2029, and AB2030 in BxPC3 cells. Fig. 23A: cytotoxicity curves; Fig. 23B: IC50 values.

[0029] FIG. 24 shows cytotoxicity curves and IC50 values of ADCs with AV-DL137 linker-payload conjugated to Isotype Antibody (non-binding control), AB2002, AB2003, AB2025, AB2029, and AB2030 in H358 cells. AB2030-MMAE ADC is a positive control for DL137 linker-payload. Fig. 24A: cytotoxicity curves; Fig. 24B: IC50 values. Fig. 24C: B7H3 and EphA2 RNA expression (Log2 values) in H358 cells, a B7H3-high and EphA2-high expressing cell line.Docket No.: AARV-020-PCT

[0030] FIG. 25 shows cytotoxicity curves and IC50 values of ADCs with AV-DL137 linker-payload conjugated to Isotype Antibody (non-binding control), AB2002, AB2003, AB2025, AB2029, and AB2030 in H661 cells. AB2030-MMAE ADC is a positive control for DL137 linker-payload. Fig. 25A: cytotoxicity curves; Fig. 25B: IC50 values. Fig. 25C: expression of B7H3 and EphA2 RNA (Log2values) in H661 cells, showing B7H3-high and EphA2-low expression.

[0031] FIG. 26 shows cytotoxicity curves and IC50 values of ADCs with AV-DL137 linker-payload conjugated to Isotype Antibody (non-binding control), AB2002, AB2003, AB2025, AB2027, AB2029, and AB2030 in PC3 cells. AB2030-MMAE ADC is a positive control for DL137 linker-payload. Fig. 26A: cytotoxicity curves; Fig. 26B: IC50 values. Fig. 26C:expression of B7H3 and EphA2 RNA (Log2values) in PC3 cells, showing B7H3-low and EphA2-high expression.

[0032] FIG. 27 shows cytotoxicity curves and IC50 values of ADCs with AV-DL137 linker-payload conjugated to AB2002, AB2003, and AB2030 in OVCAR3 cells. Fig. 27A: cytotoxicity curves; Fig. 27B: IC50 values. Fig. 27C: expression of B7H3 and EphA2 RNA (Log2values) in OVCAR3 cells, showing B7H3-med and EphA2-high expression.

[0033] FIG. 28 shows Biolayer Interferometry (BLI) analysis to monitor tandem binding of B7H3 and EphA2 antigens to two control mono-specific antibodies (AB2001, AB2003) and two bi-specific tetravalent antibodies (AB2006 and AB2015). Fig.28A: binding to EphA2 antigen followed by binding to B7H3 antigen. Fig. 28B: binding to B7H3 antigen followed by binding to EphA2 antigen.

[0034] FIG. 29 shows Biolayer Interferometry (BLI) analysis to monitor tandem binding of B7H3 and EphA2 antigens to two control mono-specific antibodies (AB2002, AB2003) and one bi-specific tetravalent antibody (AB2027). Fig.29A: binding to EphA2 antigen followed by binding to B7H3 antigen. Fig. 28B: binding to B7H3 antigen followed by binding to EphA2 antigen.

[0035] FIG. 30 shows Biolayer Interferometry (BLI) analysis to monitor tandem binding of B7H3 and EphA2 antigens to two control mono-specific antibodies (AB2002, AB2003) and two bi-specific tetravalent antibodies (AB2025, AB2030). Fig.30A: binding to EphA2 antigen followed by binding to B7H3 antigen. Fig. 30B: binding to B7H3 antigen followed by binding to EphA2 antigen.

[0036] FIG. 31 shows a synthesis scheme for compound AV-DL055B.

[0037] FIG. 32 shows a synthesis scheme for compound AV-DL112B.

[0038] FIG. 33 shows a synthesis scheme for compound AV-DL137.Docket No.: AARV-020-PCT SUMMARY

[0039] Provided herein are multi-specific antibodies (e.g., bi-specific, tri-specific, or tetra-specific antibodies) that specifically bind to epitopes of B7H3 and EphA2. In certain embodiments, the antibodies are tetravalent antibodies. The disclosure contemplates numerous configurations of epitopes to which tetravalent antibodies bind. For example, one of the four paratopes can bind to one epitope of the first target antigen (say, B7H3), and the remaining three paratopes can bind to a same or different epitope of the first target antigen and / or to the second target antigen (say, EphA2). Conversely, one of the four paratopes can bind to an epitope of a second target antigen (say, EphA2), and the remaining three paratopes can bind to the same or different epitopes of the same target antigen and / or to the first target antigen (say, B7H3). In another configuration, two of the four paratopes can bind to the same or different epitopes of a first target antigen, and the remaining two paratopes can bind to the same or different epitopes of a second target antigen. In some embodiments, the antibody has two paratopes that bind to the same epitope of a first target antigen, and two paratopes that bind to the same epitope of the second target antigen.

[0040] In one embodiment, a tetravalent antibody comprises first and second paratopes that bind the same epitope of the first target antigen in the NW / NE positions, and third and fourth paratopes that bind the same epitope of the second target antigen in the SW / SE positions. These arrangements can be reversed.

[0041] The paratopes can take a number of configurations, including, for example, two Fabs and a diabody. In other embodiments, the antibodies comprise two identical heavy chains and two identical light chains. The antibodies can be configured as immunoconjugates and, in particular, as antibody-drug conjugates comprising an antibody having a cytotoxic drug conjugated thereto. Such ADCs are useful for, among other things, the treatment of cancer.DETAILED DESCRIPTIONI. Introduction

[0042] Disclosed herein are multi-specific antibodies (e.g., bi-specific, tri-specific or tetra-specific antibodies) that bind to epitopes of B7H3 and EphA2. As discussed herein, the antibodies can be bivalent, trivalent, tetravalent, or otherwise multivalent. Antibodies described herein may bear names with an “AB” prefix. Such antibody names may be given as, e.g., “AB1234 antibody”. These names may also refer to the named antibody incorporated into an antibody-drug conjugate. Such ADCs may also be referred to as “AB1234-ADC”.

[0043] In the sequences provided herein, all B7H3 / EphA2 antibodies contain variable domains, which include their Complementarity Determining Regions (“CDRs”). It isDocket No.: AARV-020-PCT contemplated that these CDRs can be incorporated into other framework regions and retain their binding specificity.

[0044] Furthermore, variable regions and CDRs from other antibodies that bind B7H3 or EphA2 also can be used in preparing the antibodies of this disclosure.

[0045] In particular, the light chain of the antibodies AB2003 and AB2004, binding to B7H3-E1 and B7H3-E2, respectively, is taken from the antibody trastuzumab. Amino acid sequences of trastuzumab are publicly available, for example, atwww.genome.jp / dbget-bin / www_bget? D03257+D09980. Two variants for LCDR1 are known: (a) the sequence:RASQDVQTAVA (SEQ. ID NO:5), referred to as the “N30Q” variant (the gln-30 residue is underlined in the sequence), and (b) the sequence: RASQDVNTAVA (SEQ. ID NO:6), referred to as the “N30” variant (the asn-30 residue is underlined in the sequence). It is further understood that the N30 variant and the N30Q variant are functionally equivalent for use in the antibodies herein. Thus, chains comprising these LCDR1 variants may be referred to herein as “trastuzumab N30Q light chain” (SEQ. ID NO:27 and SEQ. ID NO:29) or “trastuzumab N30 light chain” (SEQ. ID NO:28 and SEQ. ID NO:30) depending on context. Trastuzumab light chain sequences (both variants) used in AB103 and AB104 further comprise a single engineered cysteine substitution at sequence GLSSPCTKSFN (SEQ. ID NO:2) where the underlined cys residue replaces with the pre-existing valine residue of trastuzumab.A. B7H3

[0046] “B7H3”, also referred to as B7-H3 and CD276, is an immune checkpoint molecule and a member of the B7 family of proteins. B7H3 is thought to have immunosuppressive properties, helping tumors evade immune responses. It is also involved in tumor growth, invasion, metastasis, and angiogenesis.

[0047] Aberrant overexpression of B7H3 has been observed in several human malignancies, including ovarian cancer, pancreatic cancer, breast cancer, non-small cell lung carcinoma, glioblastoma, melanoma, renal cell carcinoma, esophageal cancer, gastric cancer and neuroblastoma. High B7H3 expression is often associated with poor prognosis, increased metastasis, and resistance to treatment. Measures of B7H3 from tumor tissue, blood, and cerebrospinal fluid (CSF) are used as a biomarker for cancer.

[0048] B7H3 has the UniProt accession number Q5ZPR3. The protein is encoded by the CD276 gene, which is located on chromosome 15q24.1.

[0049] Antibodies that specifically bind B7H3 are described in the literature. Examples of ADCs that bind to B7H3 are ifinatamab deruxtecan (developed by Daiichi Sankyo; Nagase-Zembutsu etal., Cancer Sci. 2016 May;107(5):674-81. doi: 10.1111 / cas.12915) and vobramitamab duocarmazine (developed by MacroGenics and Synthon Biopharmaceuticals;Docket No.: AARV-020-PCT Scribner eta / ., Mol Cancer Ther. 2020; 19(11):2235-2244. doi: 10.1158 / 1535-7163. MCT-20-0116). Antibodies known to specifically bind B7H3 are commercially available, e.g., from ThermoFisher and Abeam. The CDRs of any of these antibodies can be used in the bi-specific antibodies of this disclosure.1. AB2003

[0050] Antibody AB2003 is an antibody having an IgG format and paratopes that specifically bind to a first epitope (“E1”) of B7H3 (“B7H3-E1”) (Fig. 7C). Full amino acid sequences of the heavy chain (SEQ. ID NO:26) and light chain of AB2003 (SEQ. ID NO:27, SEQ. ID NO:28) are provided herein.

[0051] Exemplary anti-B7H3 antibodies that bind to the B7H3-E1 epitope have CDR regions including the following sequences, taken from AB2003; the CDR sequences from the light chain are taken from the antibody, trastuzumab:HCDR1: GFTINAYRMH (SEQ. ID NO:19)HCDR2: YIYPNSAYTIY (SEQ. ID NO:20)HCDR3: NLRPFFALDY (SEQ. ID NO:21)LCDR1: RASQDVQTAVA (SEQ. ID NO:5) or RASQDVNTAVA (SEQ. ID NO:6) LCDR2: SASFLYS (SEQ. ID NO:22)LCDR3: QQHYTTPPT (SEQ. ID NO:23)

[0052] Exemplary anti-B7H3 antibodies that bind to the B7H3-E1 epitope can have VH and VL regions including the following sequences, taken from AB2003:

[0053] AB2003 (B7H3-E1) Heavy chain variable region (VH):EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSS (SEQ. ID NO:24)

[0054] AB2003 (B7H3-E1) Light chain variable region (VL):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK (SEQ. ID NO:25)

[0055] In the full amino acid sequences of the heavy and light chains of antibody AB2003, shown below, positions of CDRs are indicated by bold font and underlining. The engineered cysteine residue is shown in uppercase, bold, italics, and underlined font.

[0056] AB2003 (B7H3-E1) IgG Heavy chain:EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPDocket No.: AARV-020-PCT REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:26)

[0057] AB2003 (B7H3-E1) IgG Light chain:DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30 variant) (SEQ. ID NO:28)2. AB2004

[0058] Antibody AB2004 is an antibody having an IgG format and paratopes that specifically bind to a second epitope (“E2”) of B7H3 (“B7H3-E2”) (Fig. 7D). Full amino acid sequences of the heavy chain (SEQ. ID NO:35) and light chain (SEQ. ID NO:27, SEQ. ID NO: 28) of AB2004 are provided herein.

[0059] Exemplary anti-B7H3 antibodies that bind to the B7H3-E2 epitope have CDR regions including the following sequences, taken from AB2004; the CDR sequences from the light chain are taken from the antibody, trastuzumab:HCDR1: GFTIKSNYIH (SEQ. ID NO:31)HCDR2: MIYPTIGNTRY (SEQ. ID NO:32)HCDR3: GVGNDFRALDY (SEQ. ID NO:33)LCDR1: RASQDVQTAVA (SEQ. ID NO:5) or RASQDVNTAVA (SEQ. ID NO:6) LCDR2: SASFLYS (SEQ. ID NO:22)LCDR3: QQHYTTPPT (SEQ. ID NO:23)

[0060] Exemplary anti-B7H3 antibodies that bind to the B7H3-E1 epitope can have VH and VL regions including the following sequences, taken from AB2004:

[0061] AB2004 (B7H3-E2) Heavy chain variable region (VH):EVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSS (SEQ. ID NO:34)

[0062] AB2004 (B7H3-E2) Light chain variable region (VL):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK (SEQ. ID NO:25)Docket No.: AARV-020-PCT

[0063] In the full amino acid sequences of the heavy and light chains of antibody AB2004, shown below, positions of CDRs are indicated by bold font and underlining. The engineered cysteine residue is shown in uppercase, bold, italics, and underlined font.

[0064] AB2004 (B7H3-E2) IgG Heavy chain:EVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSCSTKGPSVFPLAPSS KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:35)

[0065] AB2004 (B7H3-E2) IgG Light chain:DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30 variant) (SEQ. ID NO:28)B. EphA2

[0066] “Ephrin type-A receptor 2”, also referred to as EphA2, is a transmembrane receptor tyrosine kinase (RTK) of the Eph family that binds to membrane-bound ephrin-A family ligands. EphA2 binding to ligands triggers signaling pathways both downstream (forward pathway) of the EphA2 RTK and downstream (reverse pathway) of the ligand. In normal cells, these pathways control cell adhesion. It is involved in various cellular processes, including cell adhesion, shape, and mobility. It plays a significant role in developmental events, particularly within the nervous system. EphA2 is primarily expressed in the lung alveolar type II cells and the small intestine, where it facilitates the active transport of phosphate ions across cell membranes in conjunction with sodium ions.

[0067] The significance of EphA2 in cancer cells comes from the overexpression and constitutive activation (phosphorylation by various kinases in response to oncogenic stimuli), which promotes cell migration and development of cancer stem cell (CSC)-like features. EphA2 is overexpressed in breast cancer, lung cancer, glioblastoma, pancreatic cancer,Docket No.: AARV-020-PCT colorectal cancer, prostate cancer, melanoma, renal cell carcinoma, and head and neck cancers.

[0068] EphA2 has the UniProt accession number P29317. The protein is encoded by the EPHA2 gene, which is located on chromosome 1p36.13.

[0069] Antibodies known to specifically bind EphA2 are described in the literature, for example, DS-8895 (Daiichi Sankyo; Hasegawa et al. Cancer Biol Ther.2016;17(11):1158-1167. doi: 10.1080 / 15384047.2016.1235663) and MEDI-547 (AstraZeneca, Medlmmune; Coffman etal. Cancer Res. 2003;63(22):7907-12. PMID: 14633720.). Antibodies known to bind to EphA2 are commercially available, e.g., from Abeam, R& D Systems, and Sigma-Aldrich. The CDRs of any of these antibodies can be used in the bi-specific and multispecific antibodies of this disclosure.1. AB2001

[0070] Antibody AB2001 is an antibody having an IgG format and two paratopes that specifically bind to EphA2-E1 (epitopel) (Fig. 7A). Full amino acid sequences of the heavy chain (SEQ. ID NO:44) and light chain (SEQ. ID NO:45) of AB2001 are provided herein.

[0071] Exemplary antibodies that bind to EphA2-E1 can have CDR regions including the following sequences, taken from AB2001:HCDR1: GFTIYNSSIH (SEQ. ID NO:36)HCDR2: SIRPYYSHTY (SEQ. ID NO:37) or SIRPYYSHTYY (SEQ. ID NO:92) HCDR3: YYAMDY (SEQ. ID NO:38)LCDR1: RASQSVSSAVA (SEQ. ID NO:39)LCDR2: SASSLYS (SEQ. ID NO:40)LCDR3: QQYYGYGGYPIT (SEQ. ID NO:41).

[0072] Exemplary antibodies that bind to EphA2-E1 can have VH and VL regions including the following sequences, taken from AB2002:

[0073] AB2001 (EphA2-E1) Heavy chain variable region (VH):EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSS (SEQ. ID NO:42)

[0074] AB2001 (EphA2-E1) Light chain variable region ( L):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQYYGYGGYPITFGQGTKVEIK (SEQ. ID NO:43)

[0075] In the full amino acid sequences of the heavy and light chains of antibody AB2004, shown below, positions of CDRs are indicated by bold font and underlining. The engineered cysteine residue is shown in uppercase, bold, italics, and underlined font.Docket No.: AARV-020-PCT

[0076] AB2001 (EphA2-E1) IgG Heavy chain:EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTI SADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSCSTKGPSVFPLAPSSKSTSG GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:44)

[0077] AB2001 (EphA2-E1) IgG Light chain:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQYYGYGGYPITFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPCTKSFNRGEC (SEQ. ID NO:45)2. AB2002

[0078] Antibody AB2002 is an antibody having an IgG format and two paratopes that specifically bind to EphA2-E2 (epitope2) (Fig. 7B). Full amino acid sequences of the heavy chain (SEQ. ID NO:53) and light chain (SEQ. ID NO:54) of AB2002 are provided herein.

[0079] Exemplary antibodies that bind to EphA2-E2 can have CDR regions including the following sequences, taken from AB2002:HCDR1: GFTLYYYPMH (SEQ. ID NO:47)HCDR2: SIDPSPSYTS (SEQ. ID NO:48) or SIDSPSYTSY (SEQ. ID NO:93) HCDR3: SAPSADFGLDY (SEQ. ID NO:49)LCDR1: RASQSVSSAVA (SEQ. ID NO:39)LCDR2: SASSLYS (SEQ. ID NO:40)LCDR3: QQWAYGPFT (SEQ. ID NO:50).

[0080] Exemplary antibodies that bind to EphA2-E2 can have VHand VL regions including the following sequences, taken from AB2002:

[0081] AB2002 (EphA2-E2) Heavy chain variable region (VH):EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSS (SEQ. ID NO:51)

[0082] AB2002 (EphA2-E2) Light chain variable region (VL):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIK (SEQ. ID NO:52)Docket No.: AARV-020-PCT

[0083] In the full amino acid sequences of the heavy and light chains of antibody AB2004, shown below, positions of CDRs are indicated by bold font and underlining. The engineered cysteine residue is shown in uppercase, bold, italics, and underlined font.

[0084] AB2002 (EphA2-E2) IgG Heavy chain:EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSCSTKGPSVFPLAPSS KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:53)

[0085] AB2002 (EphA2-E2) IgG Light chain:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (SEQ. ID NO:54)II. Antibodies

[0086] An “antibody” is a protein or protein complex comprising a framework region from an immunoglobulin gene, which protein or protein complex binds to a target epitope. The framework region of an immunoglobulin gene refers to relatively conserved sequences within the variable region of the immunoglobulin (Ig) heavy chain and light chain. Accordingly, the term “antibody” includes the intact tetrameric antibody, which includes two heavy immunoglobulin chains and two light immunoglobulin chains. The term also includes any binding fragment of a tetrameric antibody. The term also includes engineered antibodies in which various immunoglobulin domains are rearranged, or are added to immunoglobulin chains, for example, to create antibodies with more than two paratopes, as described herein.A. Antibody Structure

[0087] An exemplary antibody structure is an intact tetrameric antibody. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one “light” chain (about 25 kD) and one “heavy” chain (about 50-70 kD). Antibodies can be of (i) any of the five major classes of immunoglobulins, based on the identity of their heavy-chain constant domains - alpha (IgA), delta (I g D), epsilon (IgE), gamma (IgG) and mu (IgM), or (ii) subclasses (isotypes) thereof (e.g., lgG1, lgG2, lgG3, lgG4, lgA1 and lgA2). The light chains can be either lambda or kappa. In an intact antibody, a light chain comprises, from N-terminus to C-terminus, a light chain variable (VL) region and a light chain constant (CL) region. In an intact antibody, aDocket No.: AARV-020-PCT heavy chain comprises, from N-terminus to C-terminus, a heavy chain variable (VH) region, a heavy chain constant 1 (CH1) region, a hinge region, a heavy chain constant 2 (CH2) region, and a heavy chain constant 3 (CH3) region. Two light chains associate with the heavy chain regions comprising a VHregion and a CH1 region, to form two Fab (Fragment antigen-binding) domains. The light chains and heavy chains are held together by covalent bonds (e.g., a disulfide bond) and by non-covalent interactions. The combination of a VL region and a VH region forms the antigen binding domain of the antibody, also referred to as a “paratope”. The combination of the CH2 and CH3 regions are referred to collectively as the Fc (“fragment crystallizable”) region.

[0088] In the formation of antibodies, different chains or portions of chains interact with each other to form higher order structures. In this way, antibody chains or portions of them can be said to associate to form these structures. For example and without limitation, a heavy chain and light chain can associate to form a paratope. Two heavy chains can associate to form an Fc domain. Heavy chain variable regions and light chain variable regions in an scFv molecule, or in a diabody can associate to form one or more paratopes. The association can be effected through a variety of covalent and non-covalent interactions. This includes, without limitation, disulfide bonds, which can connect heavy chains with each other and light chains with heavy chains, as well as hydrogen bonding, hydrophobic interactions, and van der Waals forces. Association between chains or portions of them can occur naturally, so that the higher order structures self-assemble.

[0089] Paratopes can be formed through the association of various light chain variable regions and heavy chain variable regions in a variety of formats, discussed in more detail herein. For example, the association of a light chain and a heavy chain variable region and a polypeptide containing a heavy chain constant 1 region form a Fab domain (VL-CL: VH-CH1) that encompasses one paratope. A single chain comprising a heavy chain variable region and a light chain variable region can associate to form an scFv domain (VL: VH) that encompasses a paratope. Two chains, each comprising a heavy chain variable region and a light chain variable region can associate to form a diabody (VL-VH: VL-VH) that encompasses two paratopes. As used herein, the phrases, “a Fab encompassing a paratope,” “an scFv encompassing a paratope,” and “a diabody encompassing two paratopes,” (and so forth) can be equivalently expressed as “a paratope comprised in a Fab,” “a paratope comprised in an scFv,” and “two paratopes comprised in a diabody.”

[0090] The variable regions of both light and heavy chains in antibodies are composed of framework regions and complementarity-determining regions (CDRs) (also called “hypervariable” regions). There are three CDRs in each variable region, labeled CDR1, CDR2, and CDR3. They typically can have lengths between about 7 and about 25 amino acids. The CDRs play a role in antigen recognition. Framework regions intersperse between the CDRs and provide structural integrity, contributing to proper conformation of the CDRs for antigen binding.Docket No.: AARV-020-PCT

[0091] The phrase “CDR sequence set” refers to the 3 CDRs in the heavy chain (VH) and / or 3 CDRs in the light chain (VL) of a particular antibody. A “light chain” CDR sequence set refers to the light chain CDR sequences. A “heavy chain” CDR sequence set refers to the heavy chain CDR sequences. A “full” CDR sequence set refers to both heavy chain and light chain CDR sequences. CDRs can be predicted based on, for example, IMGT sequence alignment (The international ImMunoGeneTics information system).

[0092] The constant region interacts with other immune cells of the body.Between the Fab and Fc domains of IgG, I g D, and IgA, is the hinge region that provides flexibility to articulate antigen binding.B. Antibody Nomenclature

[0093] Antibodies can exist in natural or genetically modified forms such as humanized, human, single-chain, chimeric, synthetic, recombinant, hybrid, mutated, grafted, and in vitro generated antibodies.

[0094] As used herein, the term “monoclonal antibody” refers to a clonal preparation or composition of antibodies with a single binding specificity and affinity for a given epitope on an antigen (“monoclonal antibody composition”). A “polyclonal antibody” refers to a preparation or composition of antibodies that are raised against a single antigen, but with different binding specificities and affinities (“polyclonal antibody composition”).

[0095] As used herein, the term “chimeric antibody” refers to an antibody having amino acid sequences derived from two or more species. In one embodiment, the variable regions of both light and heavy chains correspond to the variable regions of antibodies derived from one species of mammal (e.g., mouse, rat, rabbit, etc.) with the desired specificity, affinity and capability, while the constant region contains amino acid sequences derived from another species (typically in the subject receiving the therapy, e.g., human) to avoid eliciting an immune response.

[0096] As used herein, the term “humanized antibody” refers to a chimeric antibody in which the CDRs, obtained from the VH and VL regions of a non-human antibody having the desired specificity, affinity and capability are grafted to a human framework sequence. In one embodiment, the framework residues of the humanized antibody are modified to refine and optimize the antibody specificity, affinity and capability. Humanization, i.e., substitution of non-human CDR sequences for the corresponding sequences of a human antibody, can be performed following the methods described in, e.g., U. S. Patent Nos.5,545,806; 5,569,825; 5,633,425; 5,661,016; Riechmann et al., Nature 332:323-327 (1988); Marks et al., Bio / Technology 10:779-783 (1992); Morrison, Nature 368:812-13 (1994); Fishwild et al., Nature Biotechnology 14:845-51 (1996).Docket No.: AARV-020-PCT

[0097] As used herein, the term “human antibody” refers to an antibody produced by a human or an antibody having an amino acid sequence corresponding thereto made by any technique known in the art.

[0098] As used herein, the term “immunoassay” refers to a method for detecting an analyte by detecting binding between the analyte and an antibody that recognizes the analyte.

[0099] Amino acid sequences of antibody drugs can be found, for example, at go.drugbank.com / drugs as well as at opig.stats.ox.ac.uk / webapps / sabdab-sabpred / and opig.stats.ox.ac.uk / webapps / sabdab-sabpred / therasabdab / , Raybould et al. Nucleic Acids Res.48: D383-D388, (2020).[000100] As used herein, the term “polypeptide” refers to a molecule having a sequence of natural and / or unnatural amino acids connected through peptide bonds. The term “peptide” refers to a short polypeptide, typically no more than 30 amino acids long. The amino acid sequence of a polypeptide is referred to as its “primary structure.” The term “protein” refers to a polypeptide having a secondary, tertiary and / or quaternary structure, e.g., structures stabilized by hydrogen bonds, relationships between secondary structures and structures formed of more than one protein. Proteins can be further modified by other attached moieties such as carbohydrate (glycoproteins), lipids (lipoproteins), phosphate groups (phosphoproteins) and the like.[000101] As used herein, an amino acid sequence “consists of” only the amino acids in that sequence.[000102] As used herein, a first amino acid sequence is a “fragment” of a second amino acid sequence if the second amino acid sequence comprises the first amino acid sequence. In certain embodiments, a first amino acid sequence that is a fragment of a second amino acid sequence may have up to 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 fewer amino acids than the second amino acid sequence.[000103] As used herein, a “functional equivalent” of a reference amino acid sequence is a sequence that is not identical to the reference sequence, but that contains minor alterations such as, for example, insertion, deletion or substitution of one or a few amino acids; and retains the function (e.g., antigen binding, immunogenicity) of the reference sequence to which it is equivalent. If a functionally equivalent amino acid sequence contains substitution of one or more amino acids with respect to the reference sequence, these will generally be conservative amino acid substitutions. For example, immunoglobulin chains in a functional equivalent of an antibody as disclosed herein may have at least any of 90%, 95%, 97%, 98%, 99% or 99.5% sequence identity with sequences as disclosed herein. As used herein, “sequence identity" refers to the percentage of amino acid residues that are identical atDocket No.: AARV-020-PCT corresponding positions in the alignment of two protein sequences over a defined region.Unless otherwise specified, sequence identity is determined using the Needleman-Wunsch algorithm with default parameters, by dividing the number of identical residues by the total number of residues in the aligned region and multiplying by 100. In some embodiments, a first amino acid sequence may have a given sequence identity with a second amino acid sequence and comprise the same complementarity determining regions.[000104] Also, immunoglobulin chains in a functional equivalent of an antibody as disclosed herein may have no more than any of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions per immunoglobulin chain. In some embodiments, such differences do not include changes to CDR sequences, and may be made in, e.g., antibody framework regions or spacer sequences. In other embodiments, the substitutions, additions or deletions are not made in one or both of a light chain variable region or a heavy chain variable region. (This includes variable regions of diabodies or other paratope formats.) An antibody comprising one or more engineered cysteine residues is considered a functional equivalent of the reference antibody.[000105] In certain embodiments, a heavy chain variable region can comprise a sequence at the amino terminus of either “EVQ” or “QVQ.” It has been found that heavy chains comprising the sequence “EVQ” provide certain benefits in manufacturing. In certain embodiments, a given spacer sequence between functional portions of an antibody can be exchanged for other spacer sequences. For example, a spacer given as “GGGGG” and be exchanged with “GGGGS” and vice versa. Certain of these changes may improve performance, such as manufacturability. In certain embodiments, antibody sequences having a given level of homology to a reference sequence do not contain changes in CDR sequences, light chain variable region sequences, and / or heavy chain variable region sequences.[000106] The term “cross-linked” with respect to an antibody refers to attachment of the antibody to a solid or semisolid matrix (e.g., Sepharose, beads, microtiter plate), or to another protein or antibody. For example, an antibody can be multimerized to create an antibody complex with multiple (more than 2) antigen-binding sites. The antibody can be multimerized by expressing the antibody as a high-valency isotype (e.g., IgA or IgM, which typically form complexes of 2 or 5 antibodies, respectively). Antibody multimerization can also be carried out by using a cross-linker comprising a reactive group capable of linking proteins (e.g., carbodiimide, NHS esters, etc.). Methods and compositions for cross-linking an antibody to a matrix are described, e.g., in the Abeam and New England Biolab catalogs and websites (available at abcam.com and neb.com). Cross-linker compounds with various reactive groups are described, e.g., in ThermoFisher Scientific catalog and website (available at piercenet.com).Docket No.: AARV-020-PCT C. Antibody Binding[000107] The specificity of antibody binding can be expressed in terms of the dissociation constant (Kd) of the complex between the antibody (or other targeting moiety) and its target, as compared to the dissociation constant of a complex between the antibody and a non-target molecule. A larger (higher) Kd is a parameter or property that describes a lower affinity interaction. Conversely a smaller (lower) Kd is a parameter or property that describes a higher affinity interaction or tighter binding. By way of example only, the Kd for an antibody specifically binding to a target may be in the femtomolar, picomolar, nanomolar, or micromolar range and the Kd for the antibody binding to unrelated material may be in the millimolar or higher range. Binding affinity can be in the nanomolar range (Kd lies between 10'7M and 10'9M), picomolar range (Kd lies between 10'1° M and 10'12M), or femtomolar range (Kd lies between 10’13M and 10’15M).[000108] As used herein, an antibody “specifically binds” or “is specific for” an antigen or epitope of an antigen if it binds the antigen or epitope with a Kd of less than 10'7M (i.e., in the nanomolar range). This includes, for example, Kd lower than any of the following values: 1x10-7M, 1x10-8M, 1x10"9M, IxKT10M, 1 X10’11M, or 1X10’12M. Typically, specific binding is characterized by binding the antigen with sufficient affinity that the antibody is useful as a diagnostic to detect the antigen or epitope and / or as a therapeutic agent in targeting the antigen or epitope.[000109] The term “binds” with respect to a cell type (e.g., an antibody that binds cancer cells), typically indicates that an agent binds a majority of the cells in a pure population of those cells. For example, an antibody that binds a given cell type typically binds, on average, to at least 2 out of 3 cells in a population of the indicated cells (e.g., 67, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% of the cells in the population). In some cases, binding of an antibody to a polypeptide can be assayed by comparing binding of the antibody to a cell that presents the polypeptide which is a target for binding (or lack thereof) of the antibody to that of a cell that does not express the polypeptide. One of skill in the art will recognize that some variability will arise depending on the method and / or threshold of determining binding. Affinity of an antibody for a target can be determined according to methods known in the art, e.g., as reviewed in Ernst et al. Determination of Equilibrium Dissociation Constants, Therapeutic Monoclonal Antibodies (Wiley & Sons ed. 2009).[000110] As used herein, the term “greater affinity” refers to a relative degree of antibody binding where an antibody X binds to target Y more strongly and / or with a lower dissociation constant than to target Z, and in this context antibody X has a greater affinity for target Y than for Z. Likewise, the term "lesser affinity" herein refers to a degree of antibody binding where an antibody X binds to target Y less strongly and / or with a higher dissociationDocket No.: AARV-020-PCT constant than to target Z, and in this context antibody X has a lesser affinity for target Y than for Z. The affinity of binding between an antibody and its target antigen, can be expressed as KA, which is equal to 1 / KDwhere KD is equal to kOfr / kon. The konand kOfr values can be measured using surface plasmon resonance technology, for example, using a Molecular Affinity Screening System (MASS-1) (Sierra Sensors GmbH, Hamburg, Germany).[000111] An antagonist or blocking antibody is an antibody that partially or fully blocks, inhibits or neutralizes a biological activity related to the target antigen relative to the activity under similar physiological conditions when the antibody is not present. Antagonists can be competitive, non-competitive or irreversible. A competitive antagonist is a substance that binds to a natural ligand or receptor at the same site as is used in the natural ligand-receptor interaction or binds allosterically in a manner that induces a change to prevent normal binding of the natural ligand. A non-competitive antagonist binds at a different site, on either the ligand or the receptor, than is used in the natural ligand-receptor interaction, but increases the Kd of the interaction, or lowers a signal resulting from the interaction. An irreversible inhibitor causes, e.g., covalent modifications to the receptor or to the natural ligand which prevent binding of the natural ligand to the receptor.[000112] As used herein, the term “avidity” refers to the overall stability of the binding complex between the antibody and the target antigen. It is governed by three factors, (i) the intrinsic affinity of the antibody for the antigen, (ii) the valency of the antibody, and (iii) the geometric arrangement of the interacting components. Affinity is the strength of the interaction between the antibody and a single target, whereas avidity is an accumulated strength of multiple affinities.[000113] As used herein, an antibody “preferentially binds” binds a first antigen relative to a second antigen if it binds the first antigen with greater affinity than it does the second antigen. Preferential binding can be at least any of the following: 2-fold, 5-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, 500-fold or 1000-fold greater affinity.[000114] As used herein, and antibody “blocks” or “antagonizes” the binding of a ligand to receptor when it reduces or prevents interaction of the ligand with the receptor. In embodiments, the measured level of reduction can be at least any of the following: 5%, 10%, 25%, 50%, 80%, 90%, 95%, 97.5%, 99%, 99.5%, or 99.9% of a control ligand-receptor complex ( / .e., a ligand-receptor complex in the absence of the antibody).[000115] The term “captures” with respect to an antibody target (e.g., antigen, analyte, immune complex), typically indicates that an antibody binds a majority of the antibody targets in a pure population (assuming appropriate molar ratios). For example, an antibody that binds a given antibody target typically binds to at least 2 out of 3 antibody target molecules in a solution (e.g., at least any of the following: 67%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%,Docket No.: AARV-020-PCT 95%, 96%, 97%, 98%, 99%, or 100% of the targets). A researcher of skill will recognize that some variability will arise depending on the method and / or threshold of determining binding.D. Antibody Formats[000116] The following is a non-exhaustive list of different antibody formats, all retaining antigen binding activity:(1) whole immunoglobulins (also referred to as “intact” antibodies) (two light chains and two heavy chains, e.g., a tetramer, e.g., IgG, IgA, IgD, IgE and fragments of IgM).(2) an immunoglobulin polypeptide (a light chain or a heavy chain).(3) an antibody fragment, including rearranged binding regions. These include, for example:• Fv (a monovalent or bi-valent variable region fragment, and can encompass only the variable regions (e.g., VL and / or VH),• Fab (VLC VHCH),• F(ab')2,• Fv (VLVH),• scFv (single chain Fv) (a polypeptide comprising a VLand VHjoined by a linker, e.g., a peptide linker),• (scFv)2, (optionally bi-specific),• sc(Fv)2 (optionally bi-specific),• minibody (sc(Fv)2 fused to CH3 domain)• diabody (noncovalent dimer of heavy chain variable (VH) and light chain variable ( L) regions connected by a peptide linker) (It is understood that while the VHand VLregions on a first chain can be in any order, the order of these regions on the second chain is reversed relative to these regions on the first chain relative to the order of these regions on the first chain) • triabody: trivalent sc(Fv)3 or tri-specific sc(Fv)3.• antibody fragments further include Fd (the portion of the heavy chain included in the Fab fragment) and single domain antibodies (“nanobodies” or “VHH antibodies”). A single domain antibody (sdAb) is a variable domain of either a heavy chain or a light chain, produced by recombinant methods.• Each of these can be referred to as a “domain,” e.g., an Fab domain, a diabody domain, an scFv domain, an Fc domain, etc.Docket No.: AARV-020-PCT (4) a multi-specific antibody (an antibody comprising at least two paratopes that bind to different epitopes)(5) a multivalent antibody (an antibody having two or more paratopes, including bivalent, trivalent and tetravalent antibodies)(6) a fusion protein comprising a binding portion of an immunoglobulin fused to another amino acid sequence (such as a fluorescent protein).[000117] Any of these formats can be mono-specific, or multi-specific, e.g., bispecific, tri-specific or tetra-specific.[000118] In another embodiment, and antibody provided herein can comprise an Fc effector-function-silencing mutations (or “Fc-silencing mutations”). Such antibodies comprise an Fc domain comprising one or more variants selected from: DANG Mutations (D265A and / or N297G); LALA (L234A and / or, L235A); LALA-PG (L234A, L235A, P329G), l_AI_A-PS (L234A, L235A, P331S). Fc-silencing mutations are considered functional equivalents with respect to antibody binding.E. Antibody Symmetry[000119] Antibodies comprising two heavy chains can be symmetric or asymmetric. A symmetric antibody has mirror-image parts. Typically, this will involve having identical heavy chains. An asymmetric antibody is not formatted as a mirror image. In this case, typically, the heavy chains are not identical. More specifically, “east-west” symmetry means that the “east” and “west” portions of the antibody are mirror images of each other. For example, the antibodies in Fig. 2A and 2B show east-west symmetry. In contrast, the antibodies in Fig. 2, Fig. 2C and Fig. 2D do not show east-west symmetry.[000120] An asymmetric antibody typically has two non-identical heavy chains. Usually, paratopes in the same relative position will bind different epitopes. A challenge in producing such antibodies is ensuring that the two different heavy chains pair correctly and selectively without mismatching. Mismatched associations can produce a mixture of mono-specific and bi-specific / multi-specific antibodies. Such chains may not stably associate with one another. Knobs-into-holes or Knob and Holes (KIHs) technology addresses this problem. KIHs involves engineering CH3 domains to create a “knob” in a first heavy chain and a “hole” in a second heavy chain to promote heterodimerization between the first and second heavy chains.[000121] In this approach a 'knob' variant can be obtained by replacement of a small amino acid (e.g., threonine) with a larger one (e.g., tyrosine) in the CH3 domain of an antibody (e.g., T366Y). The knob is designed to insert into a 'hole' in the CH3 domain of another antibody. In one embodiment, a 'hole' is created by replacement of a large residue (e.g., tyrosine) with a smaller one (e.g., threonine), such as in Y407T.Docket No.: AARV-020-PCT [000122] When protein domains or subdomains interact, a knob is a bulky side chain that protrudes into the opposite (“hole”) domain where it is aligned with a small side chain that makes such invasion possible. In this approach, knob and hole variants were anticipated to heterodimerize by virtue of the knob inserting into an appropriately designed hole on the partner CH3 domain. Knobs were constructed by replacing small side chains with the largest side chains, tyrosine or tryptophan. Holes of identical or similar size to the knobs were created by replacing large side chains with the smaller ones, in this case alanine or threonine. This way, two heavy chains that are knob-variants cannot homo-associate because of side chain clashes, and the homo-association of two hole-variants is less favored because of the absence of a stabilizing side-chain interaction. Additionally, a disulfide bond can be introduced near the C-terminus of the CH3 domain to further stabilize the assembled bi-specific / multi-specific antibodies. See, for example, U. S. Pat. No. 7,183,076, incorporated herein by reference.F. Spacer Moieties[000123] Engineered antibodies disclosed herein comprise functional portions attached to each other. This includes, for example, variable regions attached to each other in an scFv or diabody format, different paratope configurations (e.g., Fab, diabody, scFv) attached to each other (e.g., Fab-Diabody or Diabody-Fab), or paratopes attached to an Fc region, either on the amino side or the carboxy side. These regions or portions can be attached through spacer moieties. For example, for a tetravalent antibody of in the Fab-Diabody-Fc format, the C-terminal portion of an CH1 region of a heavy chain in the Fab region is attached to the N-terminal portion of a diabody region. The N-terminus of a diabody can be either a VL or VH region, depending on the format of the diabody region. The C-terminus of the diabody region also can be either a VHor a VL region. It is attached to the N-terminal region of an Fc region. Similarly, for a tetravalent antibody of in the Diabody-Fc-Fab format, the C-terminus of the diabody is attached to the N-terminus of the Fc region, and the C-terminus of the Fc region is attached to the N-terminus of a heavy chain of a Fab region N. The borders of these regions can be determined from the sequences herein and from antibody sequences well known in the art.[000124] Spacers can vary in length; they can be, for example, 0 (no spacer), or 1 to 50 amino acids long. The spacer can have, for example, any of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 amino acids. For example, the polypeptide spacer can have a length between any of 1 to 50, 5 to 50, 1 to 30, 1 to 25, 5 to 25, 5 to 20, 5 to 15, 5 to 10, 15, 20, 1-10 or 1-5 amino acids. In certain embodiments, a spacer is at least 5 amino acids long. In one embodiment, the spacer is or comprises a monomer or polymer of the sequence (GGGGS)n (SEQ. ID NO:7) (e.g., GGGGSGGGGSGGGGSGGGGS (SEQ. ID NO:12), (GGGGA)n (SEQ. ID NO:8), or (GGGGG)n (SEQ. ID NO:9), wherein n is any of 0, 1, 2, 3, 4, 5, 6, 7,Docket No.: AARV-020-PCT 8, 9, or 10. An embodiment of a spacer has the sequence GGGGSGGGGSEPKSSDKTHT (SEQ. ID NO:10) (e.g., to link a diabody region with an Fc region). Another embodiment of a spacer has the sequence GGGGSGGGGSGGGTG (SEQ. ID NO: 11) or GGGGSGGGGSGGGGSGGGGS (SEQ. ID NO:12) (e.g., to link an Fc region with a Fab region). Other exemplary spacers have the sequence: LEDKTHTKVEPKSS (SEQ. ID NO:13), SGSETPGTSESATPESGGG (SEQ. ID NO:14), or GTTAASGSSGGSSSGA (SEQ. ID NO:15). It is specifically contemplated that in each sequence provided herein, the linker sequence GGGGG can be replaced by GGGGS. More specifically, the GGGGSGGGGG (SEQ. ID NO: 16) can be replaced with GGGGSGGGGS (SEQ. ID NO: 17). As used herein regions or portions of an engineered antibody are connected “directly” if no spacer (0 amino acids) or “substantially directly” if a spacer of no more than 4 amino acids links them.[000125] Antibodies of Platform 2 comprise a diabody region attached to an Fc region, and an Fc region attached to a Fab region. In certain embodiments, these regions are attached directly (without a linker). That is, the C-terminus of the variable region of the diabody is directly connected to the N-terminus of the CH2 of the Fc region, and the C-terminus of the Fc region is directly connected to N-terminus of the heavy chain variable region. Reference to attachment to the CH2 region contemplates attachment to the hinge connected to CH2. In other embodiments, linkers can be selected as follows. Between variable regions of a diabody, the spacer can be between 3 and 8 amino acids and can comprise or consist of a pentameric sequence such as GGGGS. Between a diabody region and an Fc region, the spacer can be between 5 and 15 amino acids, and can comprise a pentameric sequence, such as GGGGS (SEQ. ID NO: 18). The linker can be, for example, GGGGSGGGGS (SEQ. ID NO: 17). Between the Fc region and the Fab region, the spacer can be between 10 and 20 amino acids, and can comprise a pentameric sequence, such as GGGGS (SEQ. ID NO: 18). The spacer can be, for example, GGGGSGGGGSGGGTG (SEQ. ID NO:11).[000126] Antibodies of Platform 4 comprise Fab regions attached to a Diabody region, which is attached to an Fc region. In certain embodiments, these regions are attached directly. That is, the C-terminus of the variable region of the Fab region is directly connected to the N-terminus of the diabody region, and the C-terminus of the diabody region is directly connected to N-terminus of the CH2 FC region. Reference to attachment to the CH2 region contemplates attachment to the hinge connected to CH2. In other embodiments, spacer can be selected as follows. Between an Fab region and a diabody region, the spacer can be between 10 and 20 amino acids, and can comprise a pentameric sequence, such as GGGGS (SEQ. ID NO: 18). The spacer can be, for example, GGGGSGGGGSGGGGSGGGGS (SEQ. ID NO: 12).Between variable regions of a diabody, the spacer can be between 3 and 8 amino acids and can comprise or consist of a pentameric sequence such as GGGGS (SEQ. ID NO: 18). Between a diabody region and an Fc region, the spacer can be between 5 and 15 amino acids, and canDocket No.: AARV-020-PCT comprise a pentameric sequence, such as GGGGS (SEQ. ID NO: 18). The linker can be, for example, GGGGSGGGGS (SEQ. ID NO: 15). Tables 1 and 2 show spacers between functional portions of engineered antibodies. “G4S” refers to the sequence “GGGGS” (SEQ. ID NO:18). In (G4S)n, the number n refers to the number of repetitions. Thus, for example, “(G4S)2” refers to the sequence GGGGSGGGGS (SEQ. ID NO:17). A number of “0” means no spacer, or a spacer of 0 amino acids. In any of these antibodies, spacer (G4S)n can be substituted with (G4A)n, (G5)n, or an amino acid sequence comprising an equivalent number of amino acids, which need not be an exact multiple of 5, but could be any of (X5)n + 1, 2, 3 or 4, wherein n is 0 (no spacer), 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.Table 1: Types of spacer combinations between regions of antibodies built on Platform 2 (MUTTA2™)Combination number Spacer 1: Diabody-Fc Spacer 2:Fc-Fab 1 (G4S)0 (no spacer) (G4S)0 (no spacer) 2 (G4S)2 (G4S)4 3 (G4S)2 (G4S)2 4 (G4S)2 (G4S)1 5 (G4S)2 (G4S)0 6 (G4S)1 (G4S)4 7 (G4S)1 (G4S)0 8 (G4S)0 (G4S)4 9 (G4S)0 (G4S)0 10 (G4S)2 (G4S)4Table 2: Types of spacer combinations between regions of antibodies built on Platform 4 (MUTTA4™)Combination number Spacer 3: Fab- Spacer 4:Diabody Diabody-Fc 1 (G4S)0 (no spacer) (G4S)0 (no spacer)2 (G4S)4 (G4S)2 3 (G4S)4 (G4S)1Docket No.: AARV-020-PCT 4 (G4S)4 (G4S)0 5 (G4S)3 (G4S)2 6 (G4S)2 (G4S)2 7 (G4S)1 (G4S)2 8 (G4S)0 (G4S)2 9 (G4S)0 (G4S)1III. Multivalent Antibody Platform Architectures[000127] “Multivalent” antibodies have more than one antigen binding site or paratope. For example, an antibody that has two binding sites is bivalent, an antibody with three binding sites is trivalent, and an antibody with four binding sites is tetravalent.[000128] Contemplated herein are a variety of formats for multi-specific, multivalent antibodies. Variables include the degree of valency, the format of the paratopes, and the arrangement of binding sites for particular epitopes.[000129] A multivalent antibody can have a plurality of binding sites that bind the same epitope as well as one or more binding sites that bind different epitopes. Antibodies in nature, such as IgG molecules, are typically mono-specific and bivalent. An antibody is “mono-specific” if all of its antigen binding sites bind to the same epitope. A multi-specific antibody has at least two different antigen binding sites which each bind to a different epitope or antigen. So, for example, if a bivalent antibody has antigen binding sites that each binds to a different epitope, then the antibody is bi-specific. A trivalent antibody can be monospecific, bi-specific or tri-specific. A tetravalent antibody can be monospecific, bi-specific, tri-specific or tetra-specific.[000130] As used herein, the terms “mono-specific,” “bi-specific,” “tri-specific,” and “tetra-specific,” refer to antibodies that bind one, two, three or four different epitopes, respectively. Such epitopes can be on the same or different target antigen molecules. So, for example, a tri-specific antibody can bind to an epitope of antigen A and two different epitopes of antigen B. For clarity, as used herein, an antibody can be referred to as “bi-specific,” “tri-specific,” and “tetra-specific” “as to target” when that antibody specifically binds only two, three or four different target antigens, respectively, regardless of whether it also binds different epitopes of the same target antigen.[000131] In describing antibodies herein, the orientation of various functional portions of a heavy chain or light chain is described in sequence starting from the amino terminus and proceeding to the carboxy terminus of the molecule. So, for example, an antibody that is tetrameric and bi-specific as to targets A and B, only has paratopes that bind to targets A and B. This contemplates all paratopes specifically binding to target A binding to the sameDocket No.: AARV-020-PCT epitope of target A; all paratopes binding to target B binding to the same epitope or target B; paratopes binding to target A specifically binding to different epitopes of target A; and paratopes binding to target B specifically binding to different epitopes of target B.[000132] In antibodies that have more than one light chain associated with a heavy chain, there is the issue of whether the paratopes formed by these associations bind the same or a different epitope. For example, in the antibodies shown schematically in Figs. 3A and 3B, paratopes 1 and 2 bind the same epitope, as do paratopes 3 and 4 in Figs. 2A and 2B.However, antibodies can be designed such that paratopes 1 and 2 bind different epitopes (ee, e.g., antibodies in Figs. 3C and 3D), where paratopes 3 and 4 bind different epitopes (see e.g., antibodies in Figs. 2C and 2D). Where the paratopes bind the same epitope, and the antibody is symmetric, a single light chain and a single heavy chain expressed in a cell can assemble to form the antibody. Where the paratopes bind different epitopes, and the antibody is asymmetric, the following approaches to antibody assembly can be used. In one approach, each different light chain / heavy chain pair can be expressed in a different cell, and the antibody can be assembled in vitro. In another approach, each heavy chain variable region pairs with a common light chain variable region. Such approaches are well known in the art. See, for example, U. S. Patent 8,642,745 (“Method for making multi-specific antibodies having heteromultimeric and common components”); U. S. Patent 11,033,009 (“Transgenic chicken for production of antibodies having a common light chain”); U. S. Patent 9,303,081 (“Recombinant production of mixtures of antibodies”); and U. S. Patent 11,325,982 (“Biparatopic and multiparatopic antibodies with common light chain and method of use”).[000133] Accordingly, contemplated herein are multivalent, multi-specific antibodies comprising a first paratope that specifically binds B7H3 and a second paratope that specifically binds EphA2, wherein the first and second paratopes share common light chains, light chain variable regions, or light chain CDR sequence sets.[000134] Diabodies comprise a pair of chains that associate to form two paratopes (See, e.g., Fig. 4C). Each chain comprises a VL and a VH region linked to each other. This combination is referred to as a “diabody region.” These regions can be arranged in any order, provided the regions of each partner chain are in an order consistent with formation of the diabody. In certain antibody architectures, such as shown in Figs. 2A, 2B, 3A, and 3B, both paratopes of a diabody bind the same epitope. In this configuration, each diabody region can comprise VL and H regions directed to the same epitope. In other architectures, diabodies can be designed such that the two paratopes bind different epitopes, such as shown in Figs. 2C, 2D, 3C, and 3D. In this configuration, the diabody region of a first chain includes a light or heavy chain variable region that binds a first epitope, and a heavy or light chain variable region (respectively) that binds a second epitope. In this way, each variable region can associate with the appropriate variable region on the diabody region of the other chain.Docket No.: AARV-020-PCT [000135] It is understood that references to “first,” “second,” “third,” and “fourth” regions or portions of antibodies are for nomenclature purposes only, and do not necessarily indicate specific positions of these regions or portions in an antibody, for example, specific positions in the compass rose, or equivalence between different antibody formats.A. Bivalent, Bi-specific Antibodies[000136] This disclosure contemplates a variety of bivalent, bi-specific formats. Each bivalent format comprises two paratopes. Either paratope can be configured to bind an epitope of B7H3 or and epitope of EphA2.1. Bis-Fab-Fc[000137] Referring to Fig. 5, a bi-valent antibody can have tetrameric format comprising two heavy chains and two light chains in the, e.g., IgG configuration, as shown in Fig. 5A. This format is also called “Bis-Fab-Fc” or “(Fab)2-Fc” to refer to the fact that it has two Fab domains and an Fc domain. In this case, one of the Fab paratopes binds B7H3, and the other Fab paratope binds EphA2. This antibody is comprised of two heavy chains and two light chains in which each of the heavy chains has the traditional amino-carboxy configuration of VH-CH1-CH2-CH3. Both light chains also have the traditional amino-carboxy configuration of VL-CL. The bi-specific antibody is asymmetric, that is, it has two different heavy chains, attached to each other, in this case, through a knob-and-hole arrangement.[000138] Contemplated herein is a bivalent antibody in a bis-Fab-Fc format, comprising two light chains and two heavy chains, wherein:the light chains comprise, from N-terminus to C-terminus, a light chain variable (VL) region and light chain constant (CL) region; andthe heavy chains comprise, from N-terminus to C-terminus, (1) a Fab region comprising heavy chain variable (VH) region and heavy chain constant (CH1) region, and (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region; whereinthe two light chains associate with the two Fab regions of heavy chains to form the two paratopes, and the CH2 and CH3 regions associate to form an Fc domain, and wherein one paratope specifically binds to B7H3 and the other paratope specifically binds to EphA2.2. Fab / scFv-Fc[000139] Another format, shown in Fig. 5B, is referred to as “Fab / scFv-Fc.” The antibody has two paratopes, one configured as a Fab and the other configured as scFv. This antibody comprises: (a) a first heavy chain with the configuration, from amino terminus to carboxy terminus, a VHand CH1 region, and an Fc region (CH2-CH3); (b) a second heavy chain comprising an scFv (VL-VHor VH-VL) region and an Fc region (CH2-CH3); and (c) a light chainDocket No.: AARV-020-PCT comprising a VLand CL region. The light chain and heavy chain VH / CH1 portion form a first paratope and the scFv forms a second paratope.[000140] Contemplated herein is a bivalent antibody in a Fab-Fc format, comprising one light chain and two heavy chains, wherein:the light chain comprises, from N-terminus to C-terminus, a light chain variable (VL) region and light chain constant (CL) region;one heavy chain comprises, from N-terminus to C-terminus, (1) a Fab region comprising heavy chain variable (VH) region and heavy chain constant (CH1) region, and (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region; and the other heavy chain comprises, from N-terminus to C-terminus, (1) a scFv region comprising heavy chain variable (VH) region and light chain variable ( L) region, in any order, and (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region; whereinthe light chain associates with the Fab region of one heavy chain to form one paratope, the scFv region forms one paratope, and the CH2 and CH3 regions associate to form an Fc domain; and whereinone paratope specifically binds to B7H3 and the other paratope specifically binds to EphA2.3. Bis-Diabody-Fc[000141] Another format, shown in Fig. 5C, is referred to as “bis-diabody-Fc.” The antibody has two paratopes, both comprised within a diabody. It comprises two heavy chains, each comprising a diabody region comprising a VHregion and a VLregion; and an Fc region. These are typically arranged, from amino to carboxy, asH- L, but they can be arranged as VL-Has well. Each L region of one heavy chain associates with a VH region of the other heavy chain, to form a diabody comprising first and second paratopes.[000142] Contemplated herein is a bivalent antibody in a bis-diabody-Fc format, comprising two heavy chains, wherein:the heavy chains comprise, from N-terminus to C-terminus, (1) a diabody region comprising heavy chain variable (VH) region and light chain variable (VL) region, in any order, and (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region; whereinthe diabody regions associate to form two paratopes, and the CH2 and CH3 regions associate to form an Fc domain, and whereinone paratope specifically binds to B7H3 and the other paratope specifically binds to EphA2.Docket No.: AARV-020-PCT [000143] When this bivalent antibody is bi-specific, the two heavy chains typically do not have the same amino acid sequences. In particular, the heavy chains each comprise variable regions that pair with the variable regions of the other heavy chain to form paratopes against one of the target epitopes. For increased stability, the heavy chains can be configured into knob-into-hole arrangements.a) AB2024[000144] Antibody AB2024 is an antibody having a bis-diabody-Fc format wherein one paratope specifically binds to B7H3-E1 and the other specifically binds to EphA2-E1 (Fig.8A). Full amino acid sequences of the two heavy chains of AB2024 are provided herein.[000145] In the full amino acid sequences of antibody AB2024, shown below, positions at which naturally-occurring amino acids are substituted with cysteine are indicated by bold font and underlining of the residues in heavy chain sequences LLGGPCVFLFP (SEQ. ID NO:3) and CVVVDCSHEDP (SEQ. ID NO:4).[000146] AB2024 Heavy Chain-1 Bis-Diabody-Fc (B7H3-E1 / EphA2-E1; Knob): EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSGGGGSDIQMTQSPSSL SASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPE DFATYYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPCVFLFPPK PKDTLMISRTPEVTCVVVDCSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPMVFDLPPSREEMTKNQVSLWCMVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:56)[000147] AB2024 HeavyChain-2 Bis-Diabody-Fc (EphA2-E1 / B7H3-E1; Hole): EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASV GDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFAT YYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPCVFLFPPKPKDTLMI SRTPEVTCVVVDCSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPIRELMTSNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKT TPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:57) b) AB2032[000148] Antibody AB2032 is an antibody having a bis-diabody-Fc format wherein one paratope specifically binds to B7H3-E1 and the other specifically binds to EphA2-E2 (Fig.8B). Full amino acid sequences of the two heavy chains of AB2032 are provided herein.Docket No.: AARV-020-PCT [000149] In the full amino acid sequences of antibody AB2032, shown below, positions at which naturally-occurring amino acids are substituted with cysteine are indicated by bold font and underlining of the residues in heavy chain sequences LLGGPCVFLFP (SEQ. ID NO:3) and CVVVDCSHEDP (SEQ. ID NO:4).[000150] AB2032 Heavy Chain-1 Bis-Diabody-Fc (B7H3-E1 / EphA2-E2; Knob): EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSGGGGSDIQMTQSPSSL SASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPE DFATYYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPCVFLFPPKPKD TLMISRTPEVTCVVVDCSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPMVFDLPPSREEMTKNQVSLWCMVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:58)[000151] AB2032 HeavyChain-2 Bis-Diabody-Fc (EphA2-E2 / B7H3-E1; Hole): EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQP EDFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPCVFLFPPKPK DTLMISRTPEVTCVVVDCSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPIRELMTSNQVSLSCAVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:59)B. Trivalent, Multi-specific Antibodies[000152] Trivalent antibodies can be mono-specific, bi-specific, or tri-specific.[000153] This disclosure contemplates trivalent, multi-specific antibodies. In such a format, one paratope binds to a first epitope and two paratopes bind to a second, different epitope. Alternatively, each paratope binds to a different epitope, wherein two epitopes are on the same target. Any of the paratopes can be configured to bind any target member of a Target Combination Set as disclosed herein. For example, one paratope can bind to B7H3, and two paratopes can bind to EphA2. Alternatively, one paratope can bind to an epitope of B7H3, one paratope can bind to a first epitope of EphA2, and one paratope can bind to a second epitope of EphA2. Alternatively, one paratope can bind to a first epitope of EphA2, one paratope can bind to a first epitope of B7H3, and one paratope can bind to a second epitope of B7H3.[000154] In an embodiment shown in Fig. 6, the antibody comprises a first paratope configured as a Fab domain, and second and third paratopes configured as a diabody. This format comprises: (a) a first heavy chain comprising a VHregion and a CH1 region, followedDocket No.: AARV-020-PCT by a VH-VL diabody region, and then an Fc region, (b) a second heavy chain comprising a portion comprising a VL-VH diabody region, and an Fc region (note that the VL and VH regions of the diabody region in this and all other antibodies herein can be arranged in either orientation, that is, VL-VH or VH-VL), and (c) a light chain comprising a VL region and a CL region. The light chain and the heavy chain region comprising the VH-CH1 and VL-CL regions forms a first paratope. The diabody regions combine to form a diabody producing second and third paratopes.[000155] In one embodiment, a bi-specific, trivalent antibody in an Fab1-Diabody-Fc format that specifically binds B7H3 and EphA2 comprises:a) a first light chain comprising, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) a first heavy chain comprising, from N-terminus to C-terminus:(i) a first heavy chain region comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;(ii) a first diabody region comprising a second VH region and a second VL region, in either order; and(iii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region comprising a knob or a hole;c) the second heavy chain comprising, from N-terminus to C-terminus:(i) a second diabody region comprising a third VHregion and a third VLregion, in either order; and(iii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region comprising a hole or a knob, respectively;wherein:the two heavy chains are associated by a knob-into-hole arrangement;the first light chain and the first heavy chain region form a first Fab domain comprising a first paratope;the first and second diabody regions form a diabody having a second paratope comprising the third VL region and the second VH region, and a third paratope comprising the second VL region and the third VH region.[000156] Contemplated herein is a multi-specific, trivalent antibody in a Fab1-Diabody-Fc format, comprising one light chain and two heavy chains, wherein:the light chain comprises, from N-terminus to C-terminus, a light chain variable (VL) region and light chain constant (CL) region;one heavy chain comprises, from N-terminus to C-terminus, (1) a Fab region comprising heavy chain variable (VH) region and heavy chain constant (CH1) region, (2) a diabody region comprising heavy chain variable (VH) region and light chain variable (VL) region, in any order,Docket No.: AARV-020-PCT and (3) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region; andthe other heavy chain comprises, from N-terminus to C-terminus, (1) a diabody region comprising heavy chain variable (VH) region and light chain variable (VL) region, in any order, and (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region; whereinthe light chain associates with the Fab region of one heavy chain to form one paratope, the diabody regions form two paratopes, and the CH2 and CH3 regions associate to form an Fc domain; and whereineach paratope specifically binds B7H3 or EphA2, and the paratopes, collectively, specifically bind both B7H3 and EphA2.C. Tetravalent, Multi-specific Antibodies[000157] Tetravalent antibodies can be mono-specific, bi-specific, tri-specific or tetra-specific.[000158] Contemplated herein are bi-specific / multi-specific as to target-specific, tetravalent antibodies that target antigen A and antigen B in any of the following configurations:(1) three paratopes binding to the same epitope of target A; and one paratope binding to an epitope of target B;(2) two paratopes binding to the same first epitope of target A; one paratope binding to a second epitope of target A; and one paratope binding to an epitope of target B;(3) three paratopes each binding to different epitopes of target A, and one paratope binding to an epitope of target B;(4) two paratopes binding to the same epitope of target A, and two paratopes binding to the same epitope of target B;(5) two paratopes each binding to different epitopes of target A, and two paratopes binding to the same epitope of target B;(6) two paratopes each binding to the same epitope of target A, and two paratopes binding to different epitopes of target B;(7) one paratope binding to an epitope of target A and three paratopes binding to the same epitope of target B;(8) one paratope binding to an epitope of target A, two paratopes binding to the same first epitope of target B; one paratope binding to a second epitope of target B;(9) one paratope binding to an epitope of target A and three paratopes each binding to different epitopes of Target B.The paratopes can be placed in any arrangement of the four compass positions consistent with the multi-specific nature of the antibody.Docket No.: AARV-020-PCT [000159] The four paratopes of a tetravalent antibody can be described as being positioned on a compass rose at “northwest,” “northeast,” “southeast,” “and “southwest” positions. Antibodies typically have an asymmetric shape that can be said to include an “east” side, a “west” side, a “north” (toward the N-terminus) side, and a “south” (toward the C-terminus) side. In a tetravalent antibody, for example, binding site positions could be characterized as “northeast,” “northwest,” “southeast,” and “southwest.” Accordingly, two binding sites that bind the same epitope could be related as “northwest-northeast,” “southwest-southeast,” “northeastsoutheast,” “northwest-southwest,” “northwest-southeast,” and “northeast-southwest.” See, for example, Fig. 1 and Fig. 2.[000160] This disclosure contemplates tetravalent, bi-specific / multi-specific antibodies comprising at least one paratope that binds to B7H3 and at least one paratope that binds to EphA2. In one such format, two paratopes bind to B7H3 and two paratopes bind to EphA2. In another format, one paratope binds B7H3 (or EphA2), and three paratopes bind to EphA2 (or B7H3).[000161] This disclosure further contemplates tetravalent, tri-specific antibodies comprising at least one paratope that binds to B7H3, at least one paratope that binds to a second epitope of B7H3, and at least one paratope that binds to EphA2. In one such format, one paratope binds to a first epitope of B7H3, one paratope binds a second epitope of B7H3, and two paratopes bind to EphA2.[000162] In another format, two paratopes bind to B7H3, one paratope bind to a one epitope of EphA2, and one paratope binds to a second epitope of EphA2.[000163] In another format, each paratope binds to a different epitope of the B7H3 and / or EphA2.1. Diabody-Fc-Fab[000164] An antibody platform having a “Diabody-Fc-Fab” configuration is presented in Fig. 1B and Fig. 2. This format can be referred to as Platform 2 (also referred to as MUTTA™2).[000165] In this configuration, the antibody has four paratopes, two configured as a diabody, and two configured as Fab regions. In the north-to-south, or N-terminus-to-C terminus orientations, the diabody regions are positioned north of, or N-terminal to, the Fc region, and the Fab regions are positioned south of, or C-terminal to, the Fc region. Thus, the tetravalent antibody comprises a pair of paratopes comprised a diabody region, an Fc region, and a pair of paratopes comprised in two Fab domains; wherein the antibody is arranged, from N-terminus to C-terminus: diabody, Fc region, and Fab regions.Docket No.: AARV-020-PCT [000166] The antibodies comprise first and second light chains, and first and second heavy chains. In a molecule having a diabody-Fc-Fab configuration with east-west symmetry, the sequences of the first and second light chains can be identical to each other, and the sequences of the first and second heavy chains can be identical to each other.[000167] The first light chain can comprise, from amino terminus to carboxy terminus: (1) a first light chain variable (VL) region and (2) a first light chain constant (CL) region.[000168] The second light chain can comprise, from amino terminus to carboxy terminus: (1) a second light chain variable (VL) region and (2) a second light chain constant (CL) region.[000169] The first heavy chain can comprise, from amino terminus to carboxy terminus: (1) a first Diabody region comprising a first heavy chain variable (VH) region and a third light chain variable (VL) region (in either order); (2) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region (or fragment thereof); and (3) a first heavy chain region comprising a second heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region.[000170] The second heavy chain can comprise, from amino terminus to carboxy terminus: (1) a second diabody region comprising a third heavy chain variable (VH) region and a fourth light chain variable (VL) region (in either order); (2) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region (or fragment thereof); and (3) a second heavy chain region comprising a fourth heavy chain variable (VH) region and a second heavy chain constant 1 (CH1) region.[000171] In this configuration the first and second diabody regions form two paratopes, designated here paratope 1 and paratope 2. Paratope 1 can comprise the first variable heavy region and the fourth variable light region. Paratope 2 can comprise the third variable heavy region and the third variable light region.[000172] The first light chain and the second heavy chain region form a first Fab comprising a paratope designated as paratope 3. The second light chain and the first heavy chain region form a second Fab comprising a paratope designated paratope 4.[000173] In this configuration the diabody region can be connected to the Fc region through a peptide or polypeptide spacer. Similarly, the Fc region can be connected to the Fab region through a peptide or polypeptide spacer.[000174] In the Fab domain, the light chain can be connected to the heavy chain region through one or more disulfide bonds. The Fc regions of the heavy chain also can be connected through one or more disulfide bonds, for example, between the peptide or polypeptide spacers.Docket No.: AARV-020-PCT [000175] Contemplated herein is a multi-specific, tetravalent antibody in a diabody-Fc-Fab format, comprising two heavy chains and two light chains, whereinthe light chains comprise, from N-terminus to C-terminus, a light chain variable region (VL) and light chain constant (CL) region; andthe heavy chains comprise, from N-terminus to C-terminus, (1) a diabody region comprising heavy chain variable region (VH) and light chain variable region (VL), in either order, (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region; whereinthe diabody regions are associated to form a diabody comprising two paratopes, the CH2 and CH3 regions are associated to form an Fc domain, and the light chains and the heavy chain regions are associated to form Fab domains comprising two paratopes; and whereineach paratope specifically binds B7H3 or EphA2; and the paratopes, collectively, specifically bind both B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically bind EphA2. Alternatively, two paratopes specifically bind the same epitope of B7H3 (or EphA2), one paratope specifically binds a one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.[000176] This platform contemplates monospecific, bi-specific, tri-specific, and tetra-specific configurations. In one bi-specific configuration, paratope 1 and paratope 2 bind to the same epitope; and paratope 3 and paratope 4 bind the same epitope, which is different from the epitope bound by paratopes 1 and 2. In another bi-specific configuration, all four paratopes bind the same antigen, but paratopes 1 and 2 bind different epitopes from those bound by paratopes 3 and 4. In a tri-specific configuration, two of the paratopes bind the same epitope, and the other two paratopes each bind different epitopes. In a tetra-specific configuration each paratope binds a different epitope.[000177] In certain embodiments the variable regions of the two light chains, or the entire two light chains, can be identical. This can be especially advantageous in an asymmetric antibody in which the first and second heavy chain variable regions are different, because, in the cell the same light chain associates with either heavy chain region. In comparison, if different light chains are used, they may improperly associate with the incorrect heavy chain region resulting in possibly non-functional antibodies.[000178] The heavy chain variable regions of the diabody regions can be identical, but need not be, because they will normally associate with the correct variable lighy chain regions.Docket No.: AARV-020-PCT [000179] In one format, shown in Fig. 2, a tetravalent, bi-specific / multi-specific antibody comprises first and second heavy chains comprising the same or different amino acid sequence, and comprising, from N-terminus to C-terminus: (a) a pair of paratopes comprised within a diabody (b) an Fc domain; and (c) a pair of paratopes comprised in two Fab domains. In certain embodiments, the antibodies include a pair of identical light chains that associate with the Fab regions of the heavy chains.[000180] In one embodiment, the paratopes binding B7H3 are positioned in the NW / NE positions and the paratopes binding EphA2 are positioned in the SW / SE positions. Alternatively, the paratopes binding EphA2 are positioned in the NW / NE positions and the paratopes binding B7H3 are positioned in the SW / SE positions.a) AB2006[000181] Antibody AB2006 has a symmetric diabody-Fc-Fab format and paratopes that specifically bind to B7H3-E1 (diabody NW / NE) and to EphA2-E1 (Fab SW / SE) (Fig. 9A). Full amino acid sequences of the heavy chain and light chain of AB2006 are provided herein.[000182] In the full amino acid sequences of antibody AB2006 shown below neither the heavy chain nor the light chain of this antibody carries an engineered cysteine residue.[000183] AB2006 Heavy Chain (Platform 2; Diabody-Fc-Fab; B7H3-E1 / EphA2-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSGGGGSDIQMTQSPSSL SASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPE DFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGG GGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYAD SVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:60)[000184] AB2006 Light Chain (Platform 2; Diabody-Fc-Fab; same as light chain of AB2001 binding EphA2-E1 without an engineered cysteine residue):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQYYGYGGYPITFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPVTKSFNRGEC (SEQ. ID NO:46)Docket No.: AARV-020-PCT b) AB2007[000185] Antibody AB2007 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to B7H3-E1 (diabody NW / NE) and to EphA2-E2 (Fab SW / SE) (Fig. 9B). Full amino acid sequences of the heavy chain and light chain of AB2007 are provided herein.[000186] In the full amino acid sequences of antibody AB2007 shown below neither the heavy chain nor the light chain of this antibody carries an engineered cysteine residue.[000187] AB2007 Heavy Chain (Platform 2; Diabody-Fc-Fab; B7H3-E1 / EphA2-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSGGGGSDIQMTQSPSSL SASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPE DFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGG GGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYAD SVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSASTKGPSVFPLA PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:61)[000188] AB2007 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2002 binding EphA2-E2 without an engineered cysteine residue):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (SEQ. ID NO:55)c) AB2008[000189] Antibody AB2008 has a symmetric diabody-Fc-Fab format and paratopes that specifically bind to B7H3-E2 (diabody NW / NE) and to EphA2-E2 (Fab SW / SE) (Fig. 9C). Full amino acid sequences of the heavy chain and light chain of AB2008 are provided herein.[000190] In the full amino acid sequences of antibody AB2008 shown below neither the heavy chain nor the light chain of this antibody carries an engineered cysteine residue.[000191] AB2008 Heavy Chain (Platform 2; Diabody-Fc-Fab; B7H3-E2 / EphA2-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPDocket No.: AARV-020-PCT EDFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG GGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYA DSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSASTKGPSVFPL APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY ICNVNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:62)[000192] AB2008 Light Chain (Platform 2; Diabody-Fc-Fab; same as light chain of AB2002 binding EphA2-E2 without an engineered cysteine residue):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (SEQ. ID NO:55)d) AB2009[000193] Antibody AB2009 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to B7H3-E2 (diabody NW / NE) and to EphA2-E1 (Fab SW / SE) (Fig. 9D). Full amino acid sequences of the heavy chain and light chain of AB2009 are provided herein.[000194] In the full amino acid sequences of antibody AB2009 shown below neither the heavy chain nor the light chain of this antibody carries an engineered cysteine residue.[000195] AB2009 Heavy Chain (Platform 2; Diabody-Fc-Fab; B7H3-E1 / EphA2-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSGGGGSDIQMTQSPSSL SASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPE DFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGG GGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYAD SVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:63)[000196] AB2009 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2001 binding EphA2-E1 without an engineered cysteine residue):Docket No.: AARV-020-PCT DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQYYGYGGYPITFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPVTKSFNRGEC (SEQ. ID NO:46)e) AB2010[000197] Antibody AB2010 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E2 (diabody NW / NE) and to B7H3-E2 (Fab SW / SE) (Fig. 9E). Full amino acid sequences of the heavy chain and light chain of AB2010 are provided herein.[000198] In the full amino acid sequences of antibody AB2010 shown below neither the heavy chain nor the light chain of this antibody carries an engineered cysteine residue.[000199] AB2010 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E2 / B7H3-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQP EDFATYYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG GGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYA DSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSASTKGPSVFPL APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY ICNVNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:64)[000200] AB2010 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2003 binding to B7H3-E2 without an engineered cysteine residue):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (N30Q variant) (SEQ. ID NO:29)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (N30 variant) (SEQ. ID NO:30)Docket No.: AARV-020-PCT f)AB2011[000201] Antibody AB2011 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E2 (diabody NW / NE) and to EphA2-E1 (Fab SW / SE) (Fig. 10A). Full amino acid sequences of the heavy chain and light chain of AB2011 are provided herein.[000202] In the full amino acid sequences of antibody AB2011 shown below neither the heavy chain nor the light chain of this antibody carries an engineered cysteine residue.[000203] AB2011 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E2 / EphA2- E1):EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQP EDFATYYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG GGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYA DSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:65)[000204] AB2011 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2001 binding to EphA2-E1 without an engineered cysteine residue) DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQYYGYGGYPITFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPVTKSFNRGEC (SEQ. ID NO:46)g) AB2012[000205] Antibody AB2012 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E2 (diabody NW / NE) and to B7H3-E1 (Fab SW / SE) (Fig. 9F). Full amino acid sequences of the heavy chain and light chain of AB2012 are provided herein.[000206] In the full amino acid sequences of antibody AB2012 shown below neither the heavy chain nor the light chain of this antibody carries an engineered cysteine residue.[000207] AB2012 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E2 / B7H3-E1):Docket No.: AARV-020-PCT EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQP EDFATYYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG GGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYA DSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSASTKGPSVFPLA PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:66)[000208] AB2012 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2003 binding to B7H3-E1 without an engineered cysteine residue):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (N30Q variant) (SEQ. ID NO:29)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (N30 variant) (SEQ. ID NO:30)h) AB2013[000209] Antibody AB2013 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E1 (diabody NW / NE) and to B7H3-E2 (Fab SW / SE) (Fig. 9G). Full amino acid sequences of the heavy chain and light chain of AB2013 are provided herein.[000210] In the full amino acid sequences of antibody AB2013 shown below neither the heavy chain nor the light chain of this antibody carries an engineered cysteine residue.[000211] AB2013 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E1 / B7H3-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASV GDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFAT YYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTDocket No.: AARV-020-PCT TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSG GGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVKG RFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:67)[000212] AB2013 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2004 binding to B7H3-E2 without an engineered cysteine residue):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (N30Q variant) (SEQ. ID NO:29)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (N30 variant) (SEQ. ID NO:30)i)AB2015[000213] Antibody AB2015 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E1 (diabody NW / NE) and to B7H3-E1 (Fab SW / SE) (Fig. 9H). Full amino acid sequences of the heavy chain and light chain of AB2015 are provided herein.[000214] In the full amino acid sequences of antibody AB2015 shown below neither the heavy chain nor the light chain of this antibody carries an engineered cysteine residue.[000215] AB2015 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E1 / B7H3-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASV GDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFAT YYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGG GSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADS VKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:68)Docket No.: AARV-020-PCT [000216] AB2015 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2003 binding to B7H3-E1 without an engineered cysteine residue):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (N30Q variant) (SEQ. ID NO:29)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (N30 variant) (SEQ. ID NO:30)j)AB2016[000217] Antibody AB2016 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E1 (diabody NW / NE) and to EphA2-E2 (Fab SW / SE) (Fig. 10B). Full amino acid sequences of the heavy chain and light chain of AB2016 are provided herein.[000218] In the full amino acid sequences of antibody AB2016 shown below neither the heavy chain nor the light chain of this antibody carries an engineered cysteine residue.[000219] AB2016 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E1 / EphA2- E2):EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASV GDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFAT YYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGG GSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADS VKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:69)[000220] AB2016 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2002 binding to EphA2-E2 without an engineered cysteine residue):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLDocket No.: AARV-020-PCT LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (SEQ. ID NO:55)k) AB2017[000221] Antibody AB2017 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to B7H3-E1 (diabody NW / NE) and to EphA2-E1 (Fab SW / SE) (Fig. 9A). Full amino acid sequences of the heavy chain and light chain of AB2017 are provided herein.[000222] In the full amino acid sequences of antibody AB2017, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000223] AB2017 Heavy Chain (Platform 2; Diabody-Fc-Fab; B7H3-E1 / EphA2-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSGGGGSDIQMTQSPSSL SASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPE DFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGGGG GTGEVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVKGR FTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSCSTKGPSVFPLAPSSKSTSGGT AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHT (SEQ. ID NQ:70)[000224] AB2017 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2001 binding to EphA2-E1):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQYYGYGGYPITFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPCTKSFNRGEC (SEQ. ID NO:45)l)AB2018[000225] Antibody AB2018 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E1 (diabody NW / NE) and to B7H3-E1 (Fab SW / SE) (Fig. 9H). Full amino acid sequences of the heavy chain and light chain of AB2018 are provided herein.Docket No.: AARV-020-PCT [000226] In the full amino acid sequences of antibody AB2018, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000227] AB2018 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E1 / B7H3-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASV GDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFAT YYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGGGGG TGEVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVKGRF TISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHT (SEQ. ID NO:71)[000228] AB2018 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2003 binding to B7H3-E1):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30 variant) (SEQ. ID NO:28)m) AB2021[000229] Antibody AB2021 is an asymmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E1 (diabody NW / NE) and to B7H3-E1 and B7H3-E2 (Fab SW / SE) (Fig. 11 A). Full amino acid sequences of the heavy chain and light chain of AB2021 are provided herein.[000230] In the full amino acid sequences of antibody AB2021, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at theDocket No.: AARV-020-PCT following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000231] AB2021 Heavy Chain 1 (Platform 2; Diabody-Fc-Fab; EphA2-E1 / B7H3- E1 Knob):EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASV GDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFAT YYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPMVFDLPPSREEMTKNQVSLWCMVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGGGGG TGEVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVKGRF TISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHT (SEQ. ID NO:72)[000232] AB2021 Heavy Chain 2 (Platform 2; Diabody-Fc-Fab; EphA2-E1 / B7H3- E2 Hole):EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASV GDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFAT YYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPIRELMTSNQVSLSCAVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGGGGG TGEVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVKGRF TISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSCSTKGPSVFPLAPSSKST SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK PSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:73)[000233] AB2021 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2003 / AB2004 binding to B7H3-E1 / B7H3-E2):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLDocket No.: AARV-020-PCT LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30 variant) (SEQ. ID NO:28)n) AB2022[000234] Antibody AB2022 is an asymmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E2 and EphA2-E1 (diabody NW / NE) and to B7H3-E1 and B7H3-E2 (Fab SW / SE) (Fig. 11B). Full amino acid sequences of the heavy chain and light chain of AB2022 are provided herein.[000235] In the full amino acid sequences of antibody AB2022, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000236] AB2022 Heavy Chain 1 (Platform 2; Diabody-Fc-Fab; EphA2-E2 / B7H3- E1 Knob):EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQP EDFATYYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPMVFDLPPSREEMTKNQVSLWCMVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG GGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADS VKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:74)[000237] AB2022 Heavy Chain 2 (Platform 2; Diabody-Fc-Fab; EphA2-E1 / B7H3- E2 Hole):EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASV GDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFAT YYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPIRELMTSNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKT TPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGGGGGTGE VQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVKGRFTIS ADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSCSTKGPSVFPLAPSSKSTSGGDocket No.: AARV-020-PCT TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHT (SEQ. ID NO:75)[000238] AB2022 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2003 / AB2004 binding to B7H3-E1 / B7H3-E2 (common light chain)):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30 variant) (SEQ. ID NO:28)o) AB2023[000239] Antibody AB2023 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to B7H3-E1 (diabody NW / NE) and to B7H3-E2 (Fab SW / SE) (Fig. 10C). Full amino acid sequences of the heavy chain and light chain of AB2023 are provided herein.[000240] In the full amino acid sequences of antibody AB2023, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000241] AB2023 Heavy Chain (Platform 2; Diabody-Fc-Fab; B7H3-E1 / B7H3-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSGGGGSDIQMTQSPSSL SASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPE DFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGGGG GTGEVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVKGR FTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSCSTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:76)Docket No.: AARV-020-PCT [000242] AB2023 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2004 binding to B7H3-E2):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTD FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)p) AB2027[000243] Antibody AB2027 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E2b (diabody NW / NE) and to B7H3-E1 (Fab SW / SE) (Fig. 9I). EphA2b means that the heavy chain CDRs have the sequences of AB2002 and the light chain CDRs have the sequence of AB2001. Full amino acid sequences of the heavy chain and light chain of AB2027 are provided herein.[000244] In the full amino acid sequences of antibody AB2027, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000245] AB2027 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E2b / B7H3- E1):EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQP EDFATYYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG GGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADS VKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:77)Docket No.: AARV-020-PCT [000246] AB2027 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2004 binding to B7H3-E2):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTD FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)q) AB2028[000247] Antibody AB2028 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to B7H3-E1 (diabody NW / NE) and to EphA2-E2 (Fab SW / SE) (Fig. 9B). Full amino acid sequences of the heavy chain and light chain of AB2028 are provided herein.[000248] In the full amino acid sequences of antibody AB2028, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000249] AB2028 Heavy Chain (Platform 2; Diabody-Fc-Fab; B7H3-E1 / EphA2-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSGGGGSDIQMTQSPSSL SASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPE DFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGGGG GTGEVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVKGR FTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSCSTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:78)[000250] AB2028 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2002 binding to EphA2-E2):Docket No.: AARV-020-PCT DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (SEQ. ID NO:54)r)AB2029[000251] Antibody AB2029 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E2 (diabody NW / NE) and to B7H3-E1 (Fab SW / SE) and carrying the LALA-PS motif in the Fc-effector region (Fig. 9F). Full amino acid sequences of the heavy chain and light chain of AB2029 are provided herein.[000252] In the full amino acid sequences of antibody AB2029, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2). The LALA-PS motif consists of the following substitutions in Fc domain of the heavy chain at L234A and L235A (CPAPEAAGGPSV,- SEQ. ID:94) combined with P331S (KALPASIEKTIS; SEQ. I D:95), indicated by underlining.[000253] AB2029 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E2 / B7H3-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQP EDFATYYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGGG GGTGEVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVKG RFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:79)[000254] AB2029 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2003 binding to B7H3-E1):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)orDIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDDocket No.: AARV-020-PCT FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)s) AB2033[000255] Antibody AB2033 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E2 (diabody NW / NE) and to B7H3-E2 (Fab SW / SE) (Fig. 9E). Full amino acid sequences of the heavy chain and light chain of AB2033 are provided herein.[000256] In the full amino acid sequences of antibody AB2033, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000257] AB2033 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E2 / B7H3-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQP EDFATYYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG GGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYA DSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSCSTKGPSVFPL APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY ICNVNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:80)[000258] AB2033 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2003 binding to B7H3-E2):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30 variant) (SEQ. ID NO:28)Docket No.: AARV-020-PCT t)AB2034[000259] Antibody AB2034 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to B7H3-E2 (diabody NW / NE) and to EphA2-E2 (Fab SW / SE) (Fig. 9C). Full amino acid sequences of the heavy chain and light chain of AB2034 are provided herein.[000260] In the full amino acid sequences of antibody AB2034, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000261] AB2034 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E2 / B7H3-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQP EDFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG GGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYA DSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSCSTKGPSVFPL APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY ICNVNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:81)[000262] AB2034 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2002 binding to EphA2-E2):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (SEQ. ID NO:54)u) AB2041[000263] Antibody AB2041 is a symmetric antibody having a diabody-Fc-Fab format and paratopes that specifically bind to EphA2-E2b (diabody NW / NE) and to B7H3-E1 (Fab SW / SE) and carrying the LALA-PS motif in the Fc-effector region (Fig. 9I). EphA2b means that the heavy chain CDRs have the sequences of AB2002 and the light chain CDRs have the sequence of AB2001. Full amino acid sequences of the heavy chain and light chain of AB2041 are provided herein.Docket No.: AARV-020-PCT [000264] In the full amino acid sequences of antibody AB2041, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2). The LALA-PS motif consists of the following substitutions in Fc domain of the heavy chain at L234A and L235A (CPAPEAAGGPSV,- SEQ. ID:94) combined with P331S (KALPASIEKTIS; SEQ. I D:95), indicated by underlining.[000265] AB2041 Heavy Chain (Platform 2; Diabody-Fc-Fab; EphA2-E2b / B7H3- E1):EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSS LSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQP EDFATYYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGGGSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG GGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADS VKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHT (SEQ. ID NO:96)[000266] AB2041 Light Chain (Platform 2; Diabody-Fc-Fab; Same as light chain of AB2003 binding to B7H3-E1):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTD FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)2. Fab-Diabody-Fc[000267] An antibody platform having a “Fab-Diabody-Fc” configuration is presented in Fig. 1B and Fig. 3. This format can be referred to as Platform 4. (This format isDocket No.: AARV-020-PCT also referred to as MUTTA™4. MLITTA™ stands for “Multi-epitope Targeting Tetravalent Antibody”.)[000268] In this configuration, the antibody has four paratopes, two configured as Fab regions, and two configured as a diabody. In the north-to-south, or N-terminus-to-C terminus orientations, the Fab regions are positioned north of, or more toward the N-terminus of, the diabody regions. Accordingly, both the Fab regions and the diabody regions are N-terminal of the Fc region. Thus, the tetravalent antibody comprises a pair of paratopes comprised in two Fab domains, a pair of paratopes comprised in a diabody, and an Fc region; wherein the antibody is arranged, from N-terminus to C-terminus: Fab regions, diabody, Fc region.[000269] The antibodies comprise first and second light chains, and first and second heavy chains. In a Fab-diabody-Fc configuration with east-west symmetry, the first and second light chains can be identical to each other, and the first and second heavy chains can be identical to each other.[000270] The first light chain can comprise, from amino terminus to carboxy terminus: (1) a first light chain variable (VL) region and (2) a first light chain constant (CL) region.[000271] The second light chain can comprise, from amino terminus to carboxy terminus: (1) a second light chain variable (VL) region and (2) a second light chain constant (CL) region.[000272] The first heavy chain can comprise, from amino terminus to carboxy terminus: (1) a first heavy chain region comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region; (2) a first diabody region comprising a second heavy chain variable (VH) region and a third light chain variable (VL) region (in either order); and (3) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region (or fragment thereof).[000273] The second heavy chain can comprise, from amino terminus to carboxy terminus: (1) a second heavy chain region comprising a third heavy chain variable (VH) region and a second heavy chain constant 1 (CH1) region; (2) a second diabody region comprising a fourth heavy chain variable (VH) region and a fourth light chain variable ( L) region (in either order); and (3) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region (or fragment thereof).[000274] In this configuration the first light chain and the first heavy chain region form a first Fab comprising a first paratope. The second light chain and the second heavy chain region form a second Fab comprising a second paratope.[000275] The first and second diabody regions form two paratopes, designated here paratope 3 and paratope 4. Paratope 3 can comprise the second variable heavy regionDocket No.: AARV-020-PCT and the fourth variable light region. Paratope 4 can comprise the fourth variable heavy region and the third variable light region.[000276] In this configuration the first heavy chain Fab region can be connected with the diabody region through a peptide or polypeptide spacer. Similarly, the diabody region can be connected to the Fc region through a peptide or polypeptide spacer.[000277] In the Fab region, the light chain can be connected to the heavy chain region through one or more disulfide bonds. The Fc regions of the heavy chain also can be connected through one or more disulfide bonds, for example, between the peptide or polypeptide spacers.[000278] Contemplated herein is a multi-specific, tetravalent antibody in an Fab-diabody-Fc format, comprising two heavy chains and two light chains, whereinthe light chains comprise, from N-terminus to C-terminus, a light chain variable region (VL) and light chain constant (CL) region; andthe heavy chains comprise, from N-terminus to C-terminus, (1) a heavy chain region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, (2) a diabody region comprising heavy chain variable region (VH) and light chain variable region (VL), in either order, and (3) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and; whereinthe light chains and the heavy chain regions are associated to form Fab regions comprising two paratopes, the diabody regions are associated to form a diabody comprising two paratopes, and the CH2 and CH3 regions are associated to form an Fc domain, and wherein each paratope specifically binds B7H3 or EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically EphA2. Alternatively, two paratopes specifically bind a one epitope of B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and EphA2.[000279] This platform contemplates monospecific, bi-specific, tri-specific, and tetra-specific configurations. In one bi-specific configuration, paratope 1 and paratope 2 bind to the same epitope; and paratope 3 and paratope 4 bind the same epitope, which is different from the epitope bound by paratopes 1 and 2. In another bi-specific configuration, paratope 1 and paratope 3 bind to the same epitope; and paratope 2 and paratope 4 bind the same epitope, which is different from the epitope bound by paratopes 1 and 3. In another bi-specific configuration, all four paratopes bind the same antigen, but paratopes 1 and 2 bind different epitopes from those bound by paratopes 3 and 4. In a tri-specific configuration, two of theDocket No.: AARV-020-PCT paratopes bind the same epitope, and the other two paratopes each bind different epitopes. In a tetra-specific configuration each paratope binds a different epitope.[000280] As disclosed herein, antibodies can be engineered in which paratopes that bind two different epitopes share a common light chain.[000281] In one format, shown in Fig. 3, a tetravalent, bi-specific antibody comprises first and second light chains comprising the same or different amino acid sequence, and first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus: a) a first pair of paratopes configured in an Fab format; b) a second pair of paratopes configured in a diabody format; and c) an Fc domain. In certain embodiments, the antibodies include a pair of identical light chains that associate with the Fab regions of the heavy chains.a) AB2019[000282] Antibody AB2019 is a symmetric antibody having a Fab-diabody-Fc format and paratopes that specifically bind to B7H3-E1 (Fab NW / NE) and to EphA2-E1 (diabody SW / SE) (Fig. 12A). Full amino acid sequences of the heavy chain and light chain of AB2019 are provided herein.[000283] In the full amino acid sequences of antibody AB2019, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000284] AB2019 Heavy Chain (Platform 4; Fab-Diabody-Fc; B7H3-E1 / EphA2-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTIYNSS IHWVRQAPGKGLEWVASIRPYYSHTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMD YWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGGGSEPK SSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM HEALHNHYTQKSLSLSPGK (SEQ. ID NO:82)[000285] AB2019 Light Chain (Platform 4; Fab-Diabody-Fc; Same as light chain of AB2003 binding to B7H3-E1):Docket No.: AARV-020-PCT DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTD FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)b) AB2020[000286] Antibody AB2020 is a symmetric antibody having a Fab-diabody-Fc format and paratopes that specifically bind to EphA2-E1 (Fab NW / NE) and to B7H3-E1 (diabody SW / SE) (Fig. 12B). Full amino acid sequences of the heavy chain and light chain of AB2020 are provided herein.[000287] In the full amino acid sequences of antibody AB2020, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine, may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence: VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000288] AB2020 Heavy Chain (Platform 4; Fab-Diabody-Fc; EphA2-E1 / B7H3-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTIYNSSIHWVRQAPGKGLEWVASIRPYYSHTYYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYYAMDYWGQGTLVTVSSCSTKGPSVFPLAPSSKSTSG GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWV RQAPGKGLEWVAYIYPNSAYTIYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALD YWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASF LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSEPKSSD KTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP REEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGK (SEQ. ID NO:83)[000289] AB2020 Light Chain (Platform 4; Fab-Diabody-Fc; Same as AB2001 binding to EphA2-E1):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQYYGYGGYPITFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVDocket No.: AARV-020-PCT VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPCTKSFNRGEC (SEQ. ID NO:45)c) AB2025[000290] Antibody AB2025 is a symmetric antibody having a Fab-diabody-Fc format and paratopes that specifically bind to B7H3-E1 (Fab NW / NE) and to EphA2-E2 (diabody SW / SE) (Fig. 12C). Full amino acid sequences of the heavy chain and light chain of AB2025 are provided herein.[000291] In the full amino acid sequences of antibody AB2025, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000292] AB2025 Heavy Chain (Platform 4; Fab-Diabody-Fc; B7H3-E1 / EphA2-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTLYYYP MHWVRQAPGKGLEWVASIDPSPSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSA DFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLI YSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGSE PKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:84)[000293] AB2025 Light Chain (Platform 4; Fab-Diabody-Fc; Same as light chain of AB2003 binding to B7H3-E1):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTD FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)Docket No.: AARV-020-PCT d) AB2026[000294] Antibody AB2026 is a symmetric antibody having a Fab-diabody-Fc format and paratopes that specifically bind to EphA2-E2 (Fab NW / NE) and to B7H3-E1 (diabody SW / SE) (Fig. 12D). Full amino acid sequences of the heavy chain and light chain of AB2026 are provided herein.[000295] In the full amino acid sequences of antibody AB2026, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine, may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence: VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000296] AB2026 Heavy Chain (Platform 4; Fab-Diabody-Fc; EphA2-E2 / B7H3-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSCSTKGPSVFPLAPSS KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTINAY RMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRP FFALDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLI YSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSE PKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:85)[000297] AB2026 Light Chain (Platform 4; Fab-Diabody-Fc; Same as AB2002 binding to EphA2-E2):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (SEQ. ID NO:54)e) AB2030[000298] Antibody AB2030 is a symmetric antibody having a symmetric Fab-diabody-Fc format and paratopes that specifically bind to B7H3-E1 (Fab NW / NE) and to EphA2-E2 (diabody SW / SE) and carrying the LALA-PS motif in the Fc-effector region (Fig. 12C). Full amino acid sequences of the heavy chain and light chain of AB2030 are provided herein.[000299] In the full amino acid sequences of antibody AB2030, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine, may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain atDocket No.: AARV-020-PCT the following sequence: VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2). The l_AI_A-PS motif consists of the following substitutions in Fc domain of the heavy chain at L234A and L235A (CPAPEAAGGPSV,- SEQ. ID:94) combined with P331S (KALPASIEKTIS; SEQ. I D:95), indicated by underling.[000300] AB2030 Heavy Chain 1 (Platform 4; Fab-Diabody-Fc; B7H3-E1 / EphA2- E2):EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTLYYYP MHWVRQAPGKGLEWVASIDPSPSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSA DFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLI YSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGSE PKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:86)[000301] AB2030 Light Chain (Platform 4; Fab-Diabody-Fc; Same as light chain of AB2003 binding to B7H3-E1):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTD FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)f)AB2031[000302] Antibody AB2031 is a symmetric antibody having a symmetric Fab-diabody-Fc format and paratopes that specifically bind to EphA2-E2 (Fab NW / NE) and to B7H3-E1 (diabody SW / SE) and carrying the LALA-PS motif in the Fc-effector region (Fig. 12D). Full amino acid sequences of the heavy chain and light chain of AB2031 are provided herein.[000303] In the full amino acid sequences of antibody AB2031, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine, may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain atDocket No.: AARV-020-PCT the following sequence: VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2). The l_AI_A-PS motif consists of the following substitutions in Fc domain of the heavy chain at L234A and L235A (CPAPEAAGGPSV,- SEQ. ID:94) combined with P331S (KALPASIEKTIS; SEQ. I D:95), indicated by underlining.[000304] AB2031 Heavy Chain (Platform 4; Fab-Diabody-Fc; EphA2-E2 / B7H3-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSCSTKGPSVFPLAPSS KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTINAY RMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRP FFALDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLI YSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSE PKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:87)[000305] AB2031 Light Chain (Platform 4; Fab-Diabody-Fc; Same as AB2002 binding to EphA2-E2):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (SEQ. ID NO:54)g) AB2035[000306] Antibody AB2035 is a symmetric antibody having a symmetric Fab-diabody-Fc format and paratopes that specifically bind to EphA2-E2 (Fab NW / NE) and to B7H3-E2 (diabody SW / SE) (Fig. 12E). Full amino acid sequences of the heavy chain and light chain of AB2035 are provided herein.[000307] In the full amino acid sequences of antibody AB2035, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine, may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence: VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000308] AB2035 Heavy Chain (Platform 4; Fab-Diabody-Fc; EphA2-E2 / B7H3-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSCSTKGPSVFPLAPSS KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVDocket No.: AARV-020-PCT NHKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTIKSN YIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGN DFRALDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLL IYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGS EPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:88)[000309] AB2031 Light Chain (Platform 4; Fab-Diabody-Fc; Same as AB2002 binding to EphA2-E2):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (SEQ. ID NO:54)h) AB2036[000310] Antibody AB2036 is a symmetric antibody having a symmetric Fab-diabody-Fc format and paratopes that specifically bind to B7H3-E2 (Fab NW / NE) and to EphA2-E2 (diabody SW / SE) (Fig. 12F). Full amino acid sequences of the heavy chain and light chain of AB2036 are provided herein.[000311] In the full amino acid sequences of antibody AB2036, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine, may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence: VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000312] AB2036 Heavy Chain (Platform 4; Fab-Diabody-Fc; B7H3-E2 / EphA2-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSCSTKGPSVFPLAPSS KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTLYYY PMHWVRQAPGKGLEWVASIDPSPSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPS ADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLL IYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGS EPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:89)Docket No.: AARV-020-PCT [000313] AB2036 Light Chain (Platform 4; Fab-Diabody-Fc; Same as light chain of AB2004 binding to B7H3-E2):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTD FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)i)AB2037[000314] Antibody AB2037 is a symmetric antibody having a symmetric Fab-diabody-Fc format and paratopes that specifically bind to EphA2-E2 (Fab NW / NE) and to B7H3-E2 (diabody SW / SE) and carrying the LALA-PS motif in the Fc-effector region (Fig. 12E). Full amino acid sequences of the heavy chain and light chain of AB2037 are provided herein.[000315] In the full amino acid sequences of antibody AB2037, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine, may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence: VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2). The LALA-PS motif consists of the following substitutions in Fc domain of the heavy chain at L234A and L235A (CPAPEAAGGPSV,- SEQ. ID:94) combined with P331S (KALPASIEKTIS; SEQ. I D:95), indicated by underlining.[000316] AB2037 Heavy Chain (Platform 4; Fab-Diabody-Fc; EphA2-E2 / B7H3-E1): EVQLVESGGGLVQPGGSLRLSCAASGFTLYYYPMHWVRQAPGKGLEWVASIDPSPSYTSYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSADFGLDYWGQGTLVTVSSCSTKGPSVFPLAPSS KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTIKSN YIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGN DFRALDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLL IYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGS EPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:90)Docket No.: AARV-020-PCT [000317] AB2037 Light Chain (Platform 4; Fab-Diabody-Fc; Same as AB2002 binding to EphA2-E2):DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (SEQ. ID NO:54)j)AB2038[000318] Antibody AB2038 is a symmetric antibody having a symmetric Fab-diabody-Fc format and paratopes that specifically bind to B7H3-E2 (Fab NW / NE) and to EphA2-E2 (diabody SW / SE) and carrying the LALA-PS motif in the Fc-effector region (Fig. 12F). Full amino acid sequences of the heavy chain and light chain of AB2038 are provided herein.[000319] In the full amino acid sequences of antibody AB2038, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine, may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence: VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2). The LALA-PS motif consists of the following substitutions in Fc domain of the heavy chain at L234A and L235A (CPAPEAAGGPSV,- SEQ. ID:94) combined with P331S (KALPASIEKTIS; SEQ. I D:95), indicated by underlining.[000320] AB2038 Heavy Chain (Platform 4; Fab-Diabody-Fc; B7H3-E2 / EphA2-E2): EVQLVESGGGLVQPGGSLRLSCAASGFTIKSNYIHWVRQAPGKGLEWVAMIYPTIGNTRYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGVGNDFRALDYWGQGTLVTVSSCSTKGPSVFPLAPSS KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTLYYY PMHWVRQAPGKGLEWVASIDPSPSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPS ADFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLL IYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWAYGPFTFGQGTKVEIKGGGGSGGGGS EPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:91)[000321] AB2038 Light Chain (Platform 4; Fab-Diabody-Fc; Same as light chain of AB2004 binding to B7H3-E2):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)Docket No.: AARV-020-PCT or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTD FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)k) AB2039[000322] Antibody AB2039 is a symmetric antibody having a Fab-diabody-Fc format and paratopes that specifically bind to B7H3-E1 (Fab NW / NE) and to EphA2-E2b (diabody SW / SE) (Fig. 12G). EphA2b means that the heavy chain CDRs have the sequences of AB2002 and the light chain CDRs have the sequence of AB2001. Full amino acid sequences of the heavy chain and light chain of AB2039 are provided herein.[000323] In the full amino acid sequences of antibody AB2039, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2).[000324] AB2039 Heavy Chain (Platform 4; Fab-Diabody-Fc; B7H3-E1 / EphA2- E2b):EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTLYYYP MHWVRQAPGKGLEWVASIDPSPSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSA DFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLI YSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGG GSEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:97)[000325] AB2039 Light Chain (Platform 4; Fab-Diabody-Fc; Same as light chain of AB2003 binding to B7H3-E1):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)Docket No.: AARV-020-PCT or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTD FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)I) AB2040[000326] Antibody AB2040 has a symmetric Fab-diabody-Fc format and paratopes that specifically bind to B7H3-E1 (Fab NW / NE) and to EphA2-E2b (diabody SW / SE) and carrying the LALA-PS motif in the Fc-effector region (Fig. 12G). EphA2b means that the heavy chain CDRs have the sequences of AB2002 and the light chain CDRs have the sequence of AB2001. Full amino acid sequences of the heavy chain and light chain of AB2030 are provided herein.[000327] In the full amino acid sequences of antibody AB2040, shown below, positions at which a naturally-occurring amino acid is substituted with cysteine, may be indicated by bold font and underlining. A cysteine substitution is located in the heavy chain at the following sequence: VTVSSCSTKGP (SEQ. ID NO:1), and located in the light chain at the following sequence GLSSPCTKSFN (SEQ. ID NO:2). The LALA-PS motif consists of the following substitutions in Fc domain of the heavy chain at L234A and L235A (CPAPEAAGGPSV,- SEQ. ID:94) combined with P331S (KALPASIEKTIS; SEQ. I D:95), indicated by underlining.[000328] AB2040 Heavy Chain 1 (Platform 4; Fab-Diabody-Fc; B7H3-E1 / EphA2- E2b):EVQLVESGGGLVQPGGSLRLSCAASGFTINAYRMHWVRQAPGKGLEWVAYIYPNSAYTIYADSVK GRFTISADTSKNTAYLQMNSLRAEDTAVYYCARNLRPFFALDYWGQGTLVTVSSCSTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTGGGGSGGGGGGGGTGEVQLVESGGGLVQPGGSLRLSCAASGFTLYYYP MHWVRQAPGKGLEWVASIDPSPSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSAPSA DFGLDYWGQGTLVTVSSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLI YSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQYYGYGGYPITFGQGTKVEIKGGGGSGGG GSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK (SEQ. ID NO:98)[000329] AB2040 Light Chain (Platform 4; Fab-Diabody-Fc; Same as light chain of AB2003 binding to B7H3-E1):DIQMTQSPSSLSASVGDRVTITCRASQDVQTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLDocket No.: AARV-020-PCT LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPC TKSFNRGEC (N30Q variant) (SEQ. ID NO:27)or DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTD FTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFN RGEC (N30 variant) (SEQ. ID NO:28)[000330] Bilaterally symmetric Fab-Diabody-Fc antibodies having identical heavy chains have superior manufacturability. Furthermore, in Fab-diabody-Fc antibodies, the Fab groups are positioned in the amino-terminal part of the antibody, rendering them free for binding. As such, they exhibited the best potency of any of the tetravalent, bi-specific / multi-specific antibodies described here.3. Fab-Fc-scFv (IgG-scFv)[000331] In one format, shown in Fig. 4A, a tetravalent, bi-specific / multi-specific antibody comprises first and second light chains comprising the same amino acid sequence, and first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus: a) a first pair of paratopes comprised in Fab domains; b) an Fc domain; and c) a second pair of paratopes, each comprised in an scFv domain.[000332] In one embodiment, a bi-specific / multi-specific and tetravalent antibody in an Fab-Fc-scFv format that specifically binds B7H3 and EphA2 comprises:first and second light chains and first and second heavy chains, wherein:a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VL region and a second CL region;optionally wherein the first and second light chains comprise the same amino acid sequence;c) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first heavy chain region comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a first scFv region comprising a second VHregion and a third L region, in either order; andd) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second heavy chain region comprising a third VH region and a second CH1 region;Docket No.: AARV-020-PCT (ii) a second Fc region comprising a second CH2 region and a second CH3 region;(iii) a second scFv region comprising a fourth VHregion and a fourth VL region, in either order; andoptionally wherein the first and second heavy chains comprise the same amino acid sequence;wherein:the two heavy chains are associated;the first light chain and the first heavy chain region form a first Fab domain comprising a first paratopethe second light chain and the second heavy chain region form a second Fab domain comprising a second paratopethe third VL region and a second H region of the first scFv region assemble into a third paratope; andthe fourth L region and a fourth VH region of the second scFv region assemble into a fourth paratope.[000333] Contemplated herein is a multi-specific, tetravalent antibody in a Fab-Fc-scFv format, comprising two light chains and two heavy chains, wherein:the light chains comprise, from N-terminus to C-terminus, a light chain variable (VL) region and light chain constant (CL) region; andthe heavy chains comprise, from N-terminus to C-terminus, (1) a Fab region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) an scFv region comprising a heavy chain variable (VH) region and a light chain variable (VL) region, in any order; and whereinthe two light chains associate with the two Fab regions of the heavy chains to form two paratopes, and the two scFv regions of the heavy chains form two paratopes, the CH2 and CH3 regions associate to form an Fc domain, and whereineach paratope specifically binds B7H3 or EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically bind EphA2. Alternatively, two paratopes specifically B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.4. Fab / scFv-Fc-Fab / scFv[000334] In one format, shown in Fig. 4B, a tetravalent, bi-specific / multi-specific antibody comprises two light chains and first and second heavy chains comprising different amino acid sequences. The antibody comprises, from N-terminus to C-terminus: a) a first (NW)Docket No.: AARV-020-PCT paratope comprising a Fab and a second (NE) paratope comprising an scFv; b) an Fc domain; and c) a third (SE) paratope comprising an scFv and a fourth (SW) paratope comprising a Fab.[000335] In one embodiment, a bi-specific and tetravalent antibody in an Fab / scFv / Fab-Fc-Fab / scFv format that specifically binds B7H3 and EphA2 comprises:first and second light chains, and first and second heavy chains, wherein:a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VL region and a second CL region;optionally wherein the first and second light chains comprise the same amino acid sequence;c) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first heavy chain region comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;(ii) a first Fc region comprising a first CH2 region and a first CH3 region;(iii) a second heavy chain region comprising a second VH region and a second CH1 region;d) the second heavy chain comprises, from N-terminus to C-terminus:(i) a first scFv region comprising a third VLregion and a third VHregion;(ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a second scFv region heavy chain region comprising a fourth heavy chain variable (VH) region and a fourth variable light (VL) region;wherein:the two heavy chains are associated;the first light chain and the first heavy chain region form a first Fab domain comprising a first paratope;the third VH region and the third VL region of the first scFv region form a second paratope the second light chain and the second heavy chain region form a second Fab domain comprising a third paratope; andthe fourth VH region and a fourth VL region of the second scFv region form a fourth paratope.[000336] Contemplated herein is a multi-specific, tetravalent antibody in a Fab / scFv-Fc-Fab / scFv format, comprising two light chains and two dissimilar heavy chains, wherein:the light chains comprise, from N-terminus to C-terminus, a light chain variable (VL) region and light chain constant (CL) region; andDocket No.: AARV-020-PCT one heavy chain comprises, from N-terminus to C-terminus, (1) a first Fab region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a second Fab region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, andthe other heavy chain comprises, from N-terminus to C-terminus, (1) a first scFv region comprising a heavy chain variable (VH) region and a light chain variable (VL) region, in any order (2) an Fc region comprising a heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a second scFv region comprising a heavy chain variable (VH) region and a light chain variable (VL) region, in any order; and whereinthe two light chains associate with the two Fab regions of the heavy chains to form two paratopes and the scFv regions form two paratopes, the CH2 and CH3 regions associate to form an Fc domain; and whereineach paratope specifically binds B7H3 or EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically bind EphA2. Alternatively, two paratopes specifically bind B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (B7H3), and one paratope specifically binds a second epitope of EphA2 (B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.5. Diabody-Fc-Diabody[000337] In one format, shown in Fig. 4C, a tetravalent, bi-specific / multi-specific antibody comprises first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus: a) a first pair of paratopes comprised within a diabody; b) an Fc domain; and c) a second pair of paratopes comprised within a diabody.[000338] In one embodiment, a bi-specific / multi-specific and tetravalent antibody in a Diabody-Fc-Diabody format that specifically B7H3 and EphA2 comprises:two identical heavy chains, wherein:a) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first diabody region comprising a first heavy chain variable (VH) region and a first L region, in either order;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a second diabody region comprising a second heavy chain variable (VH) region and a second VL region, in either order;b) the second heavy chain comprises, from N-terminus to C-terminus:(i) a third diabody region comprising a third heavy chain variable (VH) region and a third VLregion, in either order;Docket No.: AARV-020-PCT (ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a fourth diabody region comprising a fourth heavy chain variable (VH) region and a fourth VLregion, in either order;optionally wherein the first and second heavy chains comprise the same amino acid sequence;wherein:the two heavy chains are associated;the first and third second diabody regions form a diabody having a first paratope comprising the first VH region and the third VL region, and a second paratope comprising the third VH region and the first L region;the third and fourth diabody regions form a diabody having a third paratope comprising the fourth VH region and the second VL region, and a fourth paratope comprising the second VH region and the fourth VL region.[000339] Contemplated herein is a multi-specific, tetravalent antibody in a diabody-Fc-diabody format, comprising two heavy chains, wherein:the heavy chains comprise, from N-terminus to C-terminus, (1) a first diabody region comprising a heavy chain variable (VH) region and light chain variable (VL) region, in any order (2) an Fc region comprising a heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a second diabody region comprising a heavy chain variable (VH) region and a light chain variable (VL) region, in any order; whereinthe N-terminal diabody regions associate to form two paratopes, the C-terminal diabody regions associate to comprise two paratopes, and the CH2 and CH3 regions associate to form an Fc domain; and whereineach paratope specifically binds B7H3 and EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically bind EphA2. Alternatively, two paratopes specifically bind B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.6. Diabody-Fc-scFv[000340] In one format, shown in Fig. 4D, a tetravalent, bi-specific / multi-specific antibody comprises first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus: a) a first pair of paratopes comprised within a diabody; b) an Fc domain; and c) a second pair of paratopes, each comprised in an scFv domain.Docket No.: AARV-020-PCT [000341] In one embodiment, a bi-specific / multi-specific and tetravalent antibody in a Diabody-Fc-scFv format that specifically binds B7H3 and a EphA2 comprises:first and second heavy chains, wherein:a) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first diabody region comprising a first heavy chain variable (VH) region and a first VL region, in either order;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a first scFv region comprising a second VL region and a second H region;b) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second diabody region comprising a third heavy chain variable ( H) region and a third VL region, in either order;(ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a second scFv region comprising a fourth VH region and a fourth VL region; optionally wherein the first and second heavy chains comprise the same amino acid sequence;wherein:the two heavy chains are associated;the first and second diabody regions form a diabody having a first paratope comprising the first VHregion and the third VL region, and a second paratope comprising the third VH region and the first VLregion;the second VHregion and the second VL region of the first scFv region form a third paratope; andthe fourth VHregion and a fourth VL region of the second scFv region form a fourth paratope.[000342] Contemplated herein is a multi-specific, tetravalent antibody in a diabody-Fc-diabody format, comprising two heavy chains, wherein:the heavy chains comprise, from N-terminus to C-terminus, (1) a diabody region comprising a heavy chain variable (VH) region and light chain variable (VL) region, in any order (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a scFv region comprising a heavy chain variable (VH) region and a light chain variable (VL) region, in any order; and whereinthe diabody regions associate to form two paratopes, the scFv regions form two paratopes, and the CH2 and CH3 regions associate to form an Fc domain, and wherein each paratope specifically binds B7H3 and EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and twoDocket No.: AARV-020-PCT paratopes specifically bind EphA2. Alternatively, two paratopes specifically bind B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.7. scFv-Fc-diabody[000343] In one format, shown in Fig. 4E, a tetravalent, bi-specific / multi-specific antibody comprises first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus: a) a first pair of paratopes, each comprised in an scFv domain; b) an Fc domain; and c) a second pair of paratopes comprised within a diabody.[000344] In one embodiment, a bi-specific and tetravalent antibody in a scFv-Fc-Diabody format that specifically binds B7H3 and EphA2 comprises:first and second heavy chains, wherein:a) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first scFv region comprising a first VL region and a first VH region;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a first diabody region comprising a second heavy chain variable (VH) region and a second VLregion, in either order;d) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second scFv region comprising a third VHregion and a third VL region;(ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a second diabody region comprising a fourth heavy chain variable (VH) region and a fourth VLregion, in either order;optionally wherein the first and second heavy chains comprise the same amino acid sequence; andwherein:the two heavy chains are associated;the first VH region and the first VL region of the first scFv region form a first paratope; the third VH region and a third VL region of the second scFv region form a second paratope; andthe first and second diabody regions form a diabody having a third paratope comprising the fourth VL region and the second VH region, and a fourth paratope comprising the second VL region and the fourth VHregion.Docket No.: AARV-020-PCT [000345] Contemplated herein is a multi-specific, tetravalent antibody in a scFv-Fc-diabody format, comprising two heavy chains, wherein:the heavy chains comprise, from N-terminus to C-terminus, (1) a scFv region comprising a heavy chain variable (VH) region and a light chain variable (VL) region, in any order, (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a diabody region comprising a heavy chain variable (VH) region and light chain variable (VL) region, in any order; and whereinthe scFv regions comprise two paratopes, the diabody regions associate to form two paratopes, and the CH2 and CH3 regions associate to form an Fc domain; and wherein each paratope specifically binds B7H3 and EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically bind EphA2. Alternatively, two paratopes specifically bind B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.8. scFv-Fc-scFv[000346] In one format, shown in Fig. 4F, a tetravalent, bi-specific / multi-specific antibody comprises first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus: a) a first pair of paratopes, each comprised as an scFv region; b) an Fc domain; and c) a second pair of paratopes, each comprised as an scFv region.[000347] In one embodiment, a bi-specific and tetravalent antibody in a scFv-Fc-scFv format that specifically binds B7H3 and EphA2 comprises:a first and second heavy chains, wherein:a) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first scFv region comprising a first VL region and a first H region;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a second scFv region comprising a second VH region and a second VL region; b) the second heavy chain comprises, from N-terminus to C-terminus:(i) a third scFv region comprising a third VL region and a third VH region;(ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a fourth scFv region comprising a fourth VH region and a fourth VL region; optionally wherein the first and second heavy chains comprise the same amino acid sequence; andwherein:Docket No.: AARV-020-PCT the two heavy chains are associated;the first VHregion and the first VL region of the first scFv region form a first paratope; the second VHregion and the second VL region of the second scFv region form a first paratope;the third VHregion and a third L region of the third scFv region form a third paratope; andthe fourth VHregion and the fourth VLregion of the fourth scFv region form a fourth paratope.[000348] Contemplated herein is a multi-specific, tetravalent antibody in a scFv-Fc-diabody format, comprising two heavy chains, wherein:the heavy chains comprise, from N-terminus to C-terminus, (1) a scFv region comprising a heavy chain variable (VH) region and a light chain variable (VL) region, in any order, (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a scFv region comprising a heavy chain variable (VH) region and a light chain variable (VL) region, in any order; and whereinthe scFv regions form four paratopes, and the CH2 and CH3 regions associate to form an Fc domain, and whereineach paratope specifically binds B7H3 and EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically bind EphA2. Alternatively, two paratopes specifically bind B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.9. Fab-Fc-Diabody (IgG-Diabody)[000349] In one format, shown in Fig. 4G, a tetravalent, bi-specific / multi-specific antibody comprises first and second light chains comprising the same amino acid sequence, and first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus: a) a first pair of paratopes comprised in Fab domains; b) an Fc domain; and c) a second pair of paratopes, comprised as a diabody.[000350] In one embodiment, a bi-specific and tetravalent antibody in an Fab-Fc-Diabody format that specifically binds B7H3 and EphA2 comprises:first and second light chains and first and second heavy chains, wherein:a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VLregion and a second CL region;Docket No.: AARV-020-PCT optionally wherein the first and second light chains comprise the same amino acid sequence;c) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first heavy chain region comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a first diabody region comprising a second VH region and a third VL region, in either order; andd) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second heavy chain region comprising a third heavy chain variable (VH) region and a second heavy chain constant 1 (CH1) region;(ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a second diabody region comprising a fourth H region and a fourth VL region, in either order;optionally wherein the first and second heavy chains comprise the same amino acid sequence andwherein:the two heavy chains are associated;the first light chain and the first heavy chain region form a first Fab domain comprising a first paratope; andthe second light chain and the second heavy chain region form a second Fab domain comprising a second paratope;the first and second diabody regions form a diabody having a third paratope comprising the second VH region and the fourth VL region, and a fourth paratope comprising the fourth VH region and the third VL region.[000351] Contemplated herein is a multi-specific, tetravalent antibody in a Fab-Fc-Diabody format, comprising two light chains and two heavy chains, wherein:the light chains comprise, from N-terminus to C-terminus, a light chain variable (VL) region and light chain constant (CL) region; andthe heavy chain comprises, from N-terminus to C-terminus, (1) a Fab region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a diabody region comprising a heavy chain variable (VH) region and a light chain variable region 1 (VL) region, in any order; whereinDocket No.: AARV-020-PCT the light chains associate with the Fab regions of the heavy chains to form two paratopes, the diabody regions associate to comprise two paratopes, the CH2 and CH3 regions associate to form an Fc domain; and whereineach paratope specifically binds B7H3 and EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically bind EphA2. Alternatively, two paratopes specifically bind B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.10. scFv / Fab-Fc-Fab / scFv[000352] In one format, shown in Fig. 4H, a tetravalent, bi-specific / multi-specific antibody comprises two copies of a single light chain, and first and second heavy chains comprising the different amino acid sequences. The antibody comprises, from N-terminus to C-terminus: a) a first (NW) paratope comprising an scFv and a second (NE) paratope comprising an Fab; b) an Fc domain; and c) a third (SW) paratope comprising an Fab and a fourth (SE) paratope comprising a scFv.[000353] In one embodiment, a bi-specific and tetravalent antibody in an scFv / Fab-Fc-Fab / scFv format that specifically binds B7H3 and EphA2 comprises:[000354] first and second light chains and first and second heavy chains, wherein: a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VLregion and a second CL region;optionally wherein the first and second light chains comprise the same amino acid sequence;c) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first scFv region comprising a third VL region and a first H region;(ii) a first Fc region comprising a first CH2 region and a first CH3 region;(iii) a first heavy chain region comprising a second H region and a first CH1 region; d) the second heavy chain comprises, from N-terminus to C-terminus:(i) a first heavy chain region comprising a third heavy chain variable (VH) region and a second heavy chain constant 1 (CH1) region;(ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a second scFv region comprising a fourth heavy chain variable (VH) region and a fourth variable light (VL) region;Docket No.: AARV-020-PCT wherein:the two heavy chains are associated;the first VLregion and a first VH region of the first scFv region form a first paratope the second light chain and the second heavy chain region form a second Fab domain comprising a second paratope;the first light chain and the first heavy chain region form a first Fab domain comprising a third paratope; andthe fourth VH region and a fourth VL region of the second scFv region form a fourth paratope.[000355] Contemplated herein is a multi-specific, tetravalent antibody in a scFv / Fab-Fc-Fab / scFv format, comprising two light chains and two dissimilar heavy chains, wherein:the light chains comprise, from N-terminus to C-terminus, a light chain variable (VL) region and light chain constant (CL) region; andone heavy chain comprises, from N-terminus to C-terminus, (1) a scFv region comprising a heavy chain variable (VH) region and a light chain variable (VL) region, in any order, (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a Fab region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, andthe other heavy chain comprises, from N-terminus to C-terminus, (1) a Fab region comprising a heavy chain variable (VH) region and a heavy chain constant region 1 (CH1), (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a scFv region comprising a heavy chain variable (VH) region and a light chain variable (VL) region, in any order; and whereinthe light chains associate with the Fab regions of the heavy chains to form two paratopes, the scFv regions of the heavy chains form two paratopes, the CH2 and CH3 regions associate to form an Fc domain; and whereineach paratope specifically binds B7H3 and EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically bind EphA2. Alternatively, two paratopes specifically bind B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.11. Fab-Fc-Fab (IgG-Fab)[000356] An antibody platform having a “Fab-Fc-Fab” configuration is presented in Fig. 1C. This format can be referred to as Platform 1 (also referred to as MUTTA™1).Docket No.: AARV-020-PCT [000357] In this configuration, the antibody has four paratopes, all configured as Fab regions. In the north-to-south, or N-terminus-to-C terminus, orientations, first Fab regions are positioned north of, or N-terminal to, the Fc region, and second Fab regions are positioned south of, or C-terminal to, the Fc region. Thus, the tetravalent antibody comprises a pair of paratopes comprised Fab regions, an Fc domain, and a pair of paratopes comprised in two Fab domains; wherein the antibody is arranged, from N-terminus to C-terminus: Fab regions, Fc region, and Fab regions.[000358] In one embodiment, a bi-specific and tetravalent antibody in an Fab-Fc-Fab format that specifically binds B7H3 and EphA2 comprises:[000359] comprises first, second, third and fourth light chains and first and second heavy chains, wherein:a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VL region and a second CL region;c) the third light chain comprises, from N-terminus to C-terminus, a third VLregion and a third CL region;d) the fourth light chain comprises, from N-terminus to C-terminus, a fourth VLregion and a fourth CL region;e) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first heavy chain region comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region;(iii) a second heavy chain region comprising a second heavy chain variable (VH) region and a second heavy chain constant 1 (CH1) region; andf) the second heavy chain comprises, from N-terminus to C-terminus:(i) a third heavy chain region comprising a third heavy chain variable (VH) region and a third heavy chain constant 1 (CH1) region;(ii) a second Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region;(iii) a fourth heavy chain region comprising a fourth heavy chain variable (VH) region and a fourth heavy chain constant 1 (CH1) region; andwherein:the two heavy chains are associated;the first light chain and the first heavy chain region form a first Fab domain comprising a first paratope;Docket No.: AARV-020-PCT the second light chain and the second heavy chain region form a second Fab domain comprising a second paratope;the third chain and the third heavy chain region form a third Fab domain comprising a third paratope; andthe fourth light chain and the fourth heavy chain region form a fourth Fab domain comprising a fourth paratope.[000360] Contemplated herein is a multi-specific, tetravalent antibody in an Fab-Fc-Fab format, comprising two heavy chains and four light chains, whereinthe light chains comprise, from N-terminus to C-terminus, a light chain variable region (VL) and light chain constant (CL) region; andthe heavy chains comprise, from N-terminus to C-terminus, (1) first a heavy chain region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, (2) an Fc domain comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a second a heavy chain region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region; and whereinthe light chains and the heavy chain regions are associated to form Fab regions comprising four paratopes, and the CH2 and CH3 regions are associated to form an Fc domain, and whereineach paratope specifically binds B7H3 and EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically bind EphA2. Alternatively, two paratopes specifically bind B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.12. Fab-Fab-Fc (Fab-IgG)[000361] An antibody platform having a “Fab-Fc-Fab” configuration is presented in Fig. 1D. This format can be referred to as Platform 3 (also referred to as MUTTA™3).[000362] In this configuration, the antibody has four paratopes, all configured as Fab regions. In the north-to-south, or N-terminus-to-C terminus, orientations, first Fab regions are positioned north of, or N-terminal to, second Fab regions, which are positioned north of, or N-terminal to, the Fc region. Thus, the tetravalent antibody comprises a pair of paratopes comprised in two Fab domains, a pair of paratopes comprised in two Fab domains, and an Fc region; wherein the antibody is arranged, from N-terminus to C-terminus: Fab regions, Fab regions, and Fc region.[000363] In one embodiment, a bi-specific and tetravalent antibody in an Fab-Fab-Fc format that specifically binds B7H3 and EphA2 comprises:Docket No.: AARV-020-PCT first, second third and fourth light chains and first and second heavy chains, wherein: a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VLregion and a second CL region;c) the third light chain comprises, from N-terminus to C-terminus, a third VL region and a third CL region;d) the fourth light chain comprises, from N-terminus to C-terminus, a fourth VL region and a fourth CL region;e) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first heavy chain region comprising a first heavy chain variable ( H) region and a first heavy chain constant 1 (CH1) region;(ii) a second heavy chain region comprising a second heavy chain variable ( H) region and a second heavy chain constant 1 (CH1) region; and(iii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region;f) the second heavy chain comprises, from N-terminus to C-terminus:(i) a third heavy chain region comprising a third heavy chain variable (VH) region and a third heavy chain constant 1 (CH1) region;(ii) a fourth heavy chain region comprising a fourth heavy chain variable (VH) region and a fourth heavy chain constant 1 (CH1) region; and(iii) a second Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region;wherein:the two heavy chains are associated;the first light chain and the first heavy chain region form a first Fab domain comprising a first paratope;the second light chain and the third heavy chain region form a second Fab domain comprising a second paratope;the third chain and the second heavy chain region form a third Fab domain comprising a third paratope; andthe fourth light chain and the fourth heavy chain region form a fourth Fab domain comprising a fourth paratope.[000364] Contemplated herein is a multi-specific, tetravalent antibody in an Fab-Fab-Fc format, comprising two heavy chains and four light chains, whereinthe light chains comprise, from N-terminus to C-terminus, a light chain variable region (VL) and light chain constant (CL) region; andDocket No.: AARV-020-PCT the heavy chains comprise, from N-terminus to C-terminus, (1) first a heavy chain region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, (2) second a heavy chain region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, and (3) an Fc domain comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and; whereinthe light chains and the heavy chain regions are associated to form Fab regions comprising four paratopes, and the CH2 and CH3 regions are associated to form an Fc domain, and whereineach paratope specifically binds B7H3 and EphA2; and the paratopes, collectively, specifically bind B7H3 and EphA2, e.g., wherein, two paratopes specifically bind B7H3, and two paratopes specifically bind EphA2. Alternatively, two paratopes specifically bind B7H3 (or EphA2), one paratope specifically binds one epitope of EphA2 (or B7H3), and one paratope specifically binds a second epitope of EphA2 (or B7H3). Alternatively, each paratope specifically binds a different epitope of B7H3 and / or EphA2.[000365] Tetravalent antibodies as disclosed herein can have paratopes directed to a variety of epitopes and arranged in a variety of ways. Exemplary arrangements are described in the following Table 3 in which the paratopes are designated by compass position (NW, NE, SW, and SE), pursuant to FIGS. 1-5.Table 3Antibody Antibody Engineered Target(s) and locations Type Name CysControl AB001 Yes Isotype non-binding ADC IgG controlIgG AB2001 Yes EphA2-ElIgG AB2002 Yes EphA2-E2IgG AB2003 Yes B7H3-E1IgG AB2004 Yes B7H3-E2Bis- AB2024 Yes B7H3-El / EphA2-El Diabody-FcBis- AB2032 Yes B7H3-El / EphA2-E2 Diabody-FcPlatform AB2006 No B7H3-E1 (NW, NE) / EphA2-El 2 (SE, SW)Platform AB2007 No B7H3-E1 (NW, NE) / EphA2-E2 2 (SE, SW)Docket No.: AARV-020-PCT Platform AB2008 No B7H3-E2 (NW, NE) / EphA2-E2(SE, SW)Platform AV2009 No B7H3-E2 (NW, NE) / EphA2-El (SE, SW)Platform AB2010 No EphA2-E2 (NW, NE) / B7H3-E2(SE, SW)Platform AB2011 No EphA2-E2 (NW, NE) / EphA2-El (SE, SW)Platform AB2012 No EphA2-E2 (NW, NE) / B7H3-E1(SE, SW)Platform AB2013 No EphA2-El (NW, NE) / B7H3-E2(SE, SW)Platform AB2015 No EphA2-El (NW, NE) / B7H3-E1(SE, SW)Platform AB2016 No EphA2-El (NW, NE) / EphA2-E2(SE, SW)Platform AB2017 Yes B7H3-E1 (NW, NE) / EphA2-El (SE, SW)Platform AB2018 Yes EphA2-El (NW, NE) / B7H3-E1(SE, SW)Platform AB2021 Yes EphA2-El (NW, NE) / B7H3-E1,B7H3-E2 (SE, SW)Platform AB2022 Yes EphA2-E2, EphA2-El (NW, NE) / B7H3-E1, B7H3-E2 (SE, SW) Platform AB2023 Yes B7H3-E1 (NW, NE) / B7H3-E2(SE, SW)Platform AV2027 Yes EphA2-E2b (NW, NE) / B7H3-E1(SE, SW)Platform AB2028 Yes B7H3-E1 (NW, NE) / EphA2-E2(SE, SW)Platform AB2029 Yes EphA2-E2 (NW, NE) / B7H3-E1(SE, SW)Platform AB2033 Yes EphA2-E2 (NW, NE) / B7H3-E2(SE, SW)Docket No.: AARV-020-PCT Platform AB2034 Yes B7H3-E2 (NW, NE) / EphA2-E2 2 (SE, SW)Platform AV2041 Yes EphA2-E2b (NW, NE) / B7H3-E1 2 (SE, SW)Platform AB2019 Yes B7H3-E1 (NW, NE) / EphA2-El 4 (SE, SW)Platform AB2020 Yes EphA2-El (NW, NE) / B7H3-E1 4 (SE, SW)Platform AB2025 Yes B7H3-E1 (NW, NE) / EphA2-E2 4 (SE, SW)Platform AB2026 Yes EphA2-E2 (NW, NE) / B7H3-E1 4 (SE, SW)Platform AB2030 Yes B7H3-E1 (NW, NE) / EphA2-E2 4 (SE, SW)Platform AB2031 Yes EphA2-E2 (NW, NE) / B7H3-E1 4 (SE, SW)Platform AB2035 Yes EphA2-E2 (NW, NE) / B7H3-E2 4 (SE, SW)Platform AB2036 Yes B7H3-E2 (NW, NE) / EphA2-E2 4 (SE, SW)Platform AB2037 Yes EphA2-E2 (NW, NE) / B7H3-E2 4 (SE, SW)Platform AB2038 Yes B7H3-E2 (NW, NE) / EphA2-El 4 (SE, SW)Platform AB2039 Yes B7H3-E1 (NW, NE) / EphA2-E2b 4 (SE, SW)Platform AB2040 Yes B7H3-E1 (NW, NE) / EphA2-E2b 4 (SE, SW)[000366] Antibodies in any of these possible configurations are contemplated herein. For example, an antibody could be described as having paratopes in the NW and NE positions directed to a first epitope on a first antigen, and paratopes in the SW and SE positions directed to a second epitope on a second antigen. Alternatively, an antibody could be described as having paratopes in the NW and NE positions directed to a first epitope on a first antigen, and paratopes in the SW and SE positions directed to a second epitope on the same firstDocket No.: AARV-020-PCT antigen. Or, an antibody could be described as having a paratope in the NW position directed to a first epitope on a first antigen, a paratope in the NE position directed to a second epitope of the same first antigen, and paratopes in the SW and SE positions directed to a third epitope on a second antigen. Or, an antibody could be described as having a paratope in the NW position directed to a first epitope on a first antigen, a paratope in the SW position directed to a second epitope on the first antigen, and paratopes in the NE and SE positions directed to a third epitope on a second antigen.IV. Antibody Conjugates[000367] An antibody conjugated to a chemical entity (i.e., “payload) is referred to herein as an “antibody conjugate” or an “immunoconjugate”. Conjugation can be effected by covalent coupling or non-covalent interactions (e.g., ionic, van der Waals, electrostatic, or hydrogen bonds). The chemical entity conjugated to the antibody also can be referred to as a moiety. Chemical moieties or payloads include, without limitation, a drug, a radionuclide, a biotin, RNA, an antibiotic, a protein and a detectable moiety (e.g., a fluorophore).[000368] As used herein the term “antibody-drug conjugate” or “ADC” refers to an immunoconjugate wherein an antibody is conjugated to a drug, such as a cytotoxic drug, or an immune stimulator. Cytotoxic drugs include, without limitation, maytansinoid, DM-1, DM-4, auristatin, monomethyl auristatin E, monomethyl auristatin F, dolastatin, tubulysin, eribulin, cryptophycin, benzodiazepine, indolino-benzodiazepine, isoquinolidino-benzodiazepine, pyrrolo-benzodiazepine, alpha-amanitin, trichothene, camptothecin derivatives (SN-38, exatecan, belotecan, DXd, topotecan, samrotecan), duocarmycin, DGN549, CC1065, calicheamicin, N-acetyl calicheamicin, an enediyne antibiotic, taxane, doxorubicin derivatives, anthracycline and stereoisomers, azanofide, as well as isosteres, analogs, heterodimers, homodimers or derivatives of the foregoing. Cytotoxic drugs may also comprise any of the drug “payloads” in Colombo et al. Cancer Discov (2024) 14 (11): 2089-2108.[000369] As used herein, the term “labeled antibody” refers to an antibody conjugated to a detectable label such that the presence of a target may be detected by detecting the presence of the detectable label bound to the target (via the antibody). As used herein, the term “detectable label” refers to a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means. Examples of detectable labels are described herein and include, without limitation, colorimetric, fluorescent, chemiluminescent, enzymatic, and radioactive labels. For the purposes of the present disclosure, a detectable label can also be a moiety that does not itself produce a signal (e.g., biotin), but that binds to a second moiety that is able to produce a signal (e.g., labeled avidin or streptavidin).Docket No.: AARV-020-PCT [000370] The term “small molecule” refers to an organic or inorganic molecule having a size up to about 5000 Da, up to about 2000 Da, or up to about 1000 Da.[000371] “Potency” refers to IC50 of a compound for killing cells, e.g., in culture.[000372] Many conjugation methods are known in the art. In some embodiments, the payload is attached to the antibody through a linker. These include, without limitation, conjugation through cysteine residues, and conjugation through lysine, tyrosine or arginine residues, In some embodiments, conjugation involves covalent binding through a linker.A. Cysteine Residue Conjugation[000373] Cysteine residue conjugation involves targeting the thiol (-SH) group of cysteine residues in an antibody. This can be achieved, for example, by reducing existing disulfide bonds to expose free thiols or by engineering additional cysteine residues into the antibody. The exposed thiol groups are reactive and can be conjugated with, for example, maleimide-functionalized drugs or labels, forming stable thioether bonds.B. Lysine Residue Conjugation[000374] Lysine residue conjugation involves targeting the amine groups (-NH2) on the side chains of lysine residues. This can be done, for example, by using N-hydroxysuccinimide (NHS) esters, which react with the amine groups to form stable amide bonds.C. Linker Chemistries[000375] Payloads are conjugated to antibodies typically though linkers. Linkers include cleavable linkers and non-cleavable linkers. Cleavable linkers are typically sensitive to cleavage in the intracellular environment but not substantially sensitive to the extracellular environment, such that the conjugate is cleaved from the antibody when it is internalized. In some embodiments, the cleavable linker is a chemical cleavable linker. In some embodiments, the cleavable linker is an enzyme cleavable linker. Examples of cleavable linkers include linkers comprising hydrazone, disulfide, valine-citrulline, or beta-glucuronide groups.[000376] In some embodiments, the linker is a peptidyl linker that is cleavable by an intracellular peptidase or protease enzyme. Typically, the peptidyl linker is at least two amino acids long or at least three or four amino acids long. Cleaving agents can include cathepsins B and D and plasmin (see, e.g., Dubowchik and Walker, 1999, Pharm. Therapeutics 83:67-123). Most typical are peptidyl linkers that are cleavable by enzymes that are present in certain cells. For example, a peptidyl linker that is cleavable by the thiol-dependent protease cathepsin-B, which is highly expressed in cancerous tissue, can be used (e.g., a linker comprising a Phe-Leu or a Gly-Phe-Leu-Gly peptide). Other such linkers are described, e.g., in U. S. PatentNo.6, 214, 345. In specific embodiments, the peptidyl linker cleavable by an intracellular proteaseDocket No.: AARV-020-PCT comprises a Val-Cit linker or a Phe-Lys dipeptide (see, e.g., U. S. patent 6,214,345, which describes the synthesis of doxorubicin with the Val-Cit linker). In some embodiments, the linker is a maleimidocaproyl-L-valine-L-citrulline-p-aminobenzyloxycarbonyl linker (Mc-Val-Cit-PAB). In some embodiments, the linker-payload is Mc-VC-PAB-MMAE or vedotin:[000377] In some embodiments, the ADC is[000378] In some embodiments, the cleavable linker is pH-sensitive, i.e., sensitive to hydrolysis at certain pH values. Typically, the pH-sensitive linker is hydrolyzable under acidic conditions. For example, an acid-labile linker that is hydrolyzable in the lysosome (e.g., a hydrazone, semicarbazone, thiosemicarbazone, cis-aconitic amide, orthoester, acetal, ketal, or the like) can be used. (See, e.g., U. S. Patent Nos.5, 122,368; 5,824,805; 5,622,929; Dubowchik and Walker, 1999, Pharm. Therapeutics 83:67-123; Neville etal, 1989, Biol. Chem.264: 14653-14661.) Such linkers are relatively stable under neutral pH conditions, such as those in the blood, but are unstable at below pH 5.5 or 5.0, the approximate pH of the lysosome. In certain embodiments, the hydrolyzable linker is a thioether linker (such as, e.g., a thioether attached to the therapeutic agent via an acylhydrazone bond (see, e.g., U. S. Patent No. 5,622,929)).[000379] In some embodiments, the cleavable linker is cleavable under reducing conditions. Disulfide linkers include those that can be formed using SATA (N-succinimidyl-S-acetylthioacetate), SPDP (N-succinimidyl-3-(2-pyridyldithio)propionate), SPDB (N- succinimidyl-3-(2-pyridyldithio)butyrate) and SMPT (N-succinimidyl-oxycarbonyl- alpha- methyl-alpha-(2-pyridyl-dithio)toluene), SPDB and SMPT. {See, e.g., Thorpe etal, 1987, Cancer Res.47:5924-5931; Wawrzynczak et al, In Immunoconjugates: Antibody Conjugates in Radioimagery and Therapy of Cancer (C. W. Vogel ed., Oxford U. Press, 1987. See also U. S. PatentNo.4, 880, 935.)Docket No.: AARV-020-PCT [000380] In some embodiments, the linker-payload is ozogamicin. In some embodiments, the linker-payload is[000381] In some embodiments, the ADC is:Ab[000382] In some embodiments, the linker-payload is emtansine:Docket No.: AARV-020-PCT[000383] In some embodiments, the ADC is:[000384] In some embodiments, the linker-payload is pasudotox. In some embodiments, the ADC comprises an antibody and four pasudotox moieties conjugated thereto.[000385] In some embodiments, the linker-payload is deruxtecan:[000386] In some embodiments, the ADC is:Docket No.: AARV-020-PCT[000387] In some embodiments, the linker-payload is govitecan:[000389] In some embodiments, the linker-payload is teserine:Docket No.: AARV-020-PCT[000390] In some embodiments, the ADC is:[000391] In some embodiments, the linker-payload is AV-DL055BDocket No.: AARV-020-PCT In some embodiments, the ADC is an antibody as disclosed herein covalently attached to AV-DL055B (e.g., through the maleimide moiety).[000393] In some embodiments, the ADC is an antibody as disclosed herein covalently attached to AV-DL112B (e.g., through the maleimide moiety).[000394] In some embodiments, the linker-payload is AV-DL137:[000395] In some embodiments, the ADC is an antibody as disclosed herein covalently attached to AV-DL137 (e.g., through the maleimide moiety).[000396] The linker can also be a malonate linker (Johnson et al, 1995, Anticancer Res.15: 1387-93), a maleimidobenzoyl linker (Lau et al, 1995, Bioorg-M ed-Chem.3(10): 1299-1304), or a 3'-N-amide analog (Lau et al, 1995, Bioorg-M ed-Chem.3(10): 1305- 12). The linker also can be a non-cleavable linker, such as an maleimido-alkylene- or maleimide-aryl linker thatDocket No.: AARV-020-PCT is directly attached to the payload. The payload of an ADC comprising a non-cleavable linker is released by degradation of the antibody.[000397] Linkers also can be conjugated to an antibody through a non-natural amino acid, disulfide re-bridging, a peptide tag, glycan modification, or an enzymatic modification method used to generate site-specific immunoconjugates. In some embodiments, the linker comprises a maleimide or a dibromo maleimide. In some embodiments, the linker comprises an iodoacetamide. In some embodiments, the linker comprises a pyridyl disulfide.D. Drug-Antibody Ratio[000398] The drug-antibody ratio, or “DAR”, refers to the number of payload moieties conjugated to an antibody or the average number of payload moieties conjugated to antibodies in an ADC. DAR is a function of the number of conjugatable sites on an antibody. When disulfide bonds of an antibody are reduced, producing reactive thiols, this may allow a DAR between 1 and 12 via cysteine residue conjugation. However, the introduction of additional cysteine residues into an immunoglobulin chain can significantly increase the possible DAR. The DAR of an ADC can be, for example, at least any of the following: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 or more.E. Cysteine-substituted Antibodies[000399] A cysteine-substituted antibody is an antibody comprising at least one constant region immunoglobulin amino acid residue that has been substituted with a cysteine residue that is not present in the naturally occurring antibody. (See, e.g., Junutula et al. Nature Biotechnology, 2008:26(8):925-32, doi: 10.1038 / nbt.1480). Such a cysteine residue can also be referred to as “engineered cysteine residue.” Antibodies comprising an engineered cysteine residue are sometimes referred to as “THIOMABs™”. A non-naturally occurring substitution is one that is not isotypic. The thiol group(s) of the cysteine-substituted antibodies can be conjugated to a drug moiety (e.g., via a linker) to form a drug conjugate. Cysteine-substituted sites may be used to conjugate the antibody to other moieties, such as drug moieties or linkerdrug moieties, to create an immunoconjugate, as described further herein. In one embodiment, the substituted residues in the heavy chain constant regions can include residues A118C, T155C, S157C, V266C, H285C, R301C, V303C, T307C, G316C, Y436C and L441C. These sites are based on Ell numbering, as known In the art and described at www.imgt.org / IMGTScientificChart / Numbering / Hu_IGHGnber.html and Edelman, G. M. et al., Proc. Natl. Acad. USA, 63, 78-85 (1969). PM ID: 5257969. The substituted residues in the light chain constant region can include residue V205C (Kabat numbering; Kabat, E. A. et al., Sequences of proteins of immunological interest. 5thEdition - US Department of Health and Human Services, NIH publication no. 91-3242, pp 662,680,689 (1991)). In some embodiments, the constant region is of isotype lgG1, lgG2, lgG3 or lgG4.Docket No.: AARV-020-PCT [000400] Any form of antibody may be so engineered to incorporate a cysteine substitution. Cysteine-substituted antibodies of this disclosure preferably retain the antigen binding capability of their wild type, parent antibody counterparts. Thus, cysteine-substituted antibodies are capable of binding, preferably specifically, to antigens, e.g., tumor-associated antigens, cell surface receptor proteins, and other cell surface molecules.[000401] Cysteine-substituted antibodies of the present disclosure may be site-specifically and efficiently coupled with a thiol-reactive reagent. The thiol-reactive reagent may be a multifunctional linker reagent, a capture reagent (e.g., a biotin-linker reagent), a detection label (e.g., a fluorophore reagent), a solid phase immobilization reagent (e.g., SEPHAROSE, polystyrene, or glass), or a drug-linker intermediate. One example of a thiol-reactive reagent is N-ethyl maleimide (NEM). In an exemplary embodiment, reaction of a cysteine-substituted antibody with a biotin-linker reagent provides a biotinylated cysteine-substituted antibody by which the presence and reactivity of the engineered cysteine residue may be detected and measured. Reaction of a cysteine-substituted antibody with a multifunctional linker reagent provides a cysteine-substituted antibody with a functionalized linker which may be further reacted with a drug moiety reagent or other label. Reaction of a cysteine-substituted antibody with a drug-linker intermediate provides a cysteine-substituted antibody drug conjugate.V. Nucleic Acids, Recombinant Cells And Methods Of Making[000402] Provided herein are nucleic acid molecules encoding immunoglobulin chains of the antibodies of this disclosure. The antibodies of this disclosure can comprise a plurality of different polypeptides assembled into an antibody. For example, an antibody can comprise two identical heavy chains and two identical light chains. Alternatively, an antibody can comprise two different heavy chains. Further combinations of different polypeptides are possible, such as, for example, two different heavy chains and one or two different light chains. Therefore, further provided herein are nucleic acid molecules or collections of nucleic acid molecules that, as an ensemble, encode polypeptides which, when assembled, produce the antibodies of this disclosure.A. Nucleic Acid Molecules[000403] Antibodies of this disclosure can be made by expressing polypeptides from nucleic acid molecules that encode them. Any person skilled in the art can generate numerous nucleotide sequences that encode the amino acid sequences of the polypeptides herein using the genetic code. Such sequences may include preferred codons of the expression system used. Nucleic acids comprising nucleotide sequences that encode heavy chain and light chain molecules can be incorporated into recombinant DNA molecules (such as expression vectors), transfected into cells, expressed by the cells in culture, harvested and purified. SuchDocket No.: AARV-020-PCT methods are well known in the fields of molecular biology, cell biology and biopharmaceutical manufacturing.[000404] A nucleic acid molecule encodes a polypeptide if it comprises a nucleotide sequence that, upon transcription and / or translation, produce the polypeptide. This includes, without limitation, contiguous nucleotide sequences that encode a polypeptide and noncontiguous nucleotide sequences that encode a polypeptide. Noncontiguous nucleotide sequences encoding a polypeptide include, for example, nucleotide sequences that include both introns and exons. Such non-coding sequences are spliced out of messenger RNAs.B. Expression Constructs and Vectors[000405] The nucleic acid molecules encoding immunoglobulin molecules can be incorporated into an expression construct for expression. An expression construct is a polynucleotide comprising an expression control sequence operatively linked with a heterologous nucleotide sequence (i.e., a sequence to which the expression control sequence is not normally connected to in nature) that is to be expressed.[000406] An expression control sequence is a nucleotide sequence that regulates transcription and / or translation of a nucleotide sequence operatively linked thereto. Expression control sequences include promoters, enhancers, repressors (transcription regulatory sequences) and ribosome binding sites (translation regulatory sequences). Suitable regulatory sequences may be derived from a variety of sources, including bacterial, fungal, viral, mammalian, or insect genes.[000407] A nucleotide sequence is “operatively linked” with an expression control sequence when the expression control sequence functions in a cell to regulate transcription of the nucleotide sequence. This includes initiating transcription of the nucleotide sequence through an interaction between a polymerase and a transcriptional regulatory sequence such as, for example, a promoter.[000408] Promoters typically used in eukaryotic expression systems include, without limitation, the following. CMV (Cytomegalovirus) promoter, EF-1a (Elongation Factor-1 alpha) promoter, SV40 (Simian Virus 40) promoter, PGK (Phosphoglycerate kinase) promoter, CAG promoter, AOX1 (Alcohol oxidase 1) promoter, GAP (Glyceraldehyde-3-phosphate dehydrogenase) promoter. Some promoters used in yeast, such as Saccharomyces cerevisiae, are ADH (Alcohol dehydrogenase) promoter, GAL1 and GAL10 promoters.[000409] An expression vector is a polynucleotide comprising an expression construct and sequences sufficient for replication in a host cell or insertion into a host chromosome. A vector can comprise any intermediary vehicle for a nucleic acid molecule which enables said nucleic acid molecule, for example, to be introduced into prokaryotic and / or eukaryotic cells and / or integrated into a genome. Exemplary vectors for transfection of cellsDocket No.: AARV-020-PCT include, for example, a plasmid, a viral vector (e.g., a retrovirus, a lentivirus, an adenovirus, a papovavirus (e.g., SV40, polyoma) a parvovirus (e.g., adeno-associated virus), or a herpes simplex virus), a bacterial artificial chromosome, and a yeast artificial chromosome. The term “plasmid” as used herein generally refers to a construct of extrachromosomal genetic material, usually a circular DNA duplex, which can replicate independently of chromosomal DNA. The vector should be compatible with the host cell used. Other sequences, such as an origin of replication, DNA restriction sites, enhancers, and sequences conferring inducibility of transcription may be incorporated into the expression vector.[000410] The recombinant expression vectors may also contain a marker gene which facilitates the selection of host cells transformed or transfected with a vector for expressing an antibody described herein.[000411] The recombinant expression vectors may also contain expression cassettes which encode a fusion moiety which provides increased expression or stability of the recombinant peptide; increased solubility of the recombinant peptide; or that aids in the purification of the target recombinant peptide by acting as a ligand in affinity purification, including for example, tags and labels described herein (e.g., a (His)e tag). A recombinant peptide and its fusion moiety are collectively termed a “fusion protein.” Further, a proteolytic cleavage site may be added to the fusion protein to allow separation of the recombinant peptide from the fusion moiety subsequent to purification of the fusion protein. Typical fusion expression vectors include pGEX (Amrad Corp., Melbourne, Australia), pMAL (New England Biolabs, Beverly, MA) and pRIT5 (Pharmacia, Piscataway, NJ) which fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the recombinant protein.[000412] The recombinant expression vectors may also contain a signal peptide. Signal peptides can be used for efficient secretion of recombinant proteins. Signal peptides are short N-terminal amino acid sequences, to direct proteins to the secretory pathway. In some embodiments, the recombinant expression vector comprises a signal peptide.C. Recombinant Cells[000413] Antibodies as disclosed herein can be made by culturing cells engineered to express nucleic acid constructs encoding immunoglobulin polypeptides. In some embodiments, the antibodies disclosed herein are made by culturing cells engineered to express nucleic acid constructs encoding immunoglobulin polypeptides.[000414] The recombinant host cell can be generated using any cell suitable for producing a polypeptide, for example, suitable for producing an antibody. For example, to introduce a nucleic acid (e.g., a vector) into a cell, the cell may be transfected or transformed, depending upon the vector employed. In some embodiments, the recombinant host cell is generated by introducing a nucleic acid (e.g., a vector) into a cell. In some embodiments, a cellDocket No.: AARV-020-PCT is transfected with the nucleic acid to generate the recombinant host cell. In some embodiments a cell is transformed with the nucleic acid to generate the recombinant host cell. In some embodiments a cell is transfected with the nucleic acid to generate the recombinant host cell.[000415] Methods for transfecting cells with recombinant DNA molecules are known in the art and include, for example, electroporation, liposomes and exosomes, and transfection via viral vectors.[000416] Suitable host cells include a wide variety of prokaryotic and eukaryotic host cells. For example, the proteins described herein may be expressed in a mammalian cell (e.g., CHO, 293); an insect cell (e.g., in Sf9 cell or a high five (BTI-Tn-5B1-4) cell); a yeast cell (e.g., Pichia pastoris or and Saccharomyces cerevisiae) a bacterial cell (e.g., E. coli) or a plant cell (e.g., Arabidopsis).[000417] Mammalian cells that may be suitable include, among others: a Chinese hamster ovary (CHO) cell, an NSO cell, an SP2 / 0 cell, a human embryonic kidney HEK 293 cell, or a Per. C6 cell). Suitable expression vectors for directing expression in mammalian cells generally include a promoter (e.g., derived from viral genomes such as polyoma, Adenovirus 2, cytomegalovirus and Simian Virus 40), as well as other transcriptional and translational control sequences. Examples of mammalian expression vectors include pCDM8, pOmni, and pMT2PC.[000418] Yeast and fungal host cells suitable for expressing an antibody include, but are not limited to Saccharomyces cerevisiae, Schizosaccharomyces pombe, the genera Pichia or Kluyveromyces and various species of the genus Aspergillus. Examples of vectors for expression in yeast S. cerevisiae include pYepSed, pMFa, pJRY88, and pYES2 (Invitrogen Corporation, San Diego, CA). Protocols for the transformation of yeast and fungi are well known to those of ordinary skill in the art.D. Antibody Production[000419] Transformed / transfected cells are grown under suitable conditions that allow them to express the recombinant antibody.[000420] The number of different immunoglobulin chains that must be expressed in a cell to produce an antibody depends on the configuration of the antibody. Generally, fewer different chains results in more effective antibody assembly.[000421] Antibodies described herein may contain one or two different heavy chains, depending on architecture. Antibodies with the same heavy chain require only production of only one heavy chain in a cell, and they will associate naturally. If the antibody comprises different heavy chains, two polypeptides are produced, and knob-into-hole arrangements can facilitate proper assembly of antibodies, discouraging association of two “knob” chains or two “hole” chains.Docket No.: AARV-020-PCT [000422] Light chains also will associate with their respective heavy chains. Where the antibody comprises two of the same heavy chains, then only one light chain needs to be expressed. However, in certain asymmetric antibodies, two different light chains may be needed to associate with the asymmetric heavy chains. It may be noted that in certain situations, it may be possible to produce two different paratopes that comprise different heavy chain regions and the same light chain. An antibody against a target or epitope having a particular light chain can be created by creating libraries in which the light chain variable region is fixed and the heavy chain variable region of antibodies in the library have diverse sequences. Accordingly, if such a library or libraries are screened against different epitopes, then antibodies that bind each different epitope will have the same light chain variable region and different heavy chain variable regions.[000423] For cells that secrete the recombinant antibody chains, culture medium comprising the immunoglobulin molecules is harvested and antibodies are purified from the medium using protein A or protein G chromatography, which binds specifically to the Fc region of antibodies. In certain embodiments, recombinant cells containing light chains and / or heavy chains are lysed, and the immunoglobulin chains are purified from the lysate using standard biochemical procedures.[000424] If desired, purified antibodies are then conjugated with payloads of the kind and by the methods of which are described herein.VI. Pharmaceutical Compositions[000425] Further provided herein is a composition comprising an antibody, immunoconjugate, nucleic acid molecule, vector or recombinant cell described herein, optionally with a suitable diluent, e.g., a pharmaceutically acceptable carrier. The composition can for example, comprise one or more antibodies or immunoconjugates.[000426] In one embodiment, a pharmaceutical composition comprises an antibody or immunoconjugate as described herein formulated in a pharmaceutically acceptable carrier. The composition is typically formulated for intravenous injection. Accordingly, the carrier can be an aqueous carrier, such as sterilized water or saline solution. The composition can further comprise ingredients to stabilize the antibody molecules. These can include, for example, sugars and polyols, which assist in freeze-drying. Mannitol also can be used as a tonicity adjuster and bulking agent in freeze-dried formulations. Surfactants, such as polysorbate 20 or polysorbate 80 are also commonly used in monoclonal antibody formulations. Buffers, such as phosphate, histidine and citrate, are frequently used in such formulations.[000427] In some embodiments, the composition is formulated for intradermal injection. In some embodiments, the composition is formulated for subcutaneous injection. In some embodiments, the composition is formulated for intramuscular injection. In someDocket No.: AARV-020-PCT embodiments, the composition is formulated for intraperitoneal injection. In some embodiments, the composition is formulated for intranodal injection. In some embodiments, the composition is formulated for intrasplenic injection.[000428] The compositions described herein can be prepared by perse known methods for the preparation of pharmaceutically acceptable compositions that can be administered to subjects, such that an effective quantity of the active substance is combined in a mixture with a pharmaceutically acceptable vehicle.[000429] The term “pharmaceutically acceptable” refers to a carrier that is compatible with the other ingredients of a pharmaceutical composition and can be safely administered to a subject. The term is used synonymously with “physiologically acceptable” and “pharmacologically acceptable”. Pharmaceutical compositions and techniques for their preparation and use are known to those of skill in the art in light of the present disclosure. For a detailed listing of suitable pharmacological compositions and techniques for their administration one may refer to texts such as Remington’s Pharmaceutical Sciences, 17thed. 1985; Brunton et al., “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” McGraw-Hill, 2005; University of the Sciences in Philadelphia (eds.), “Remington: The Science and Practice of Pharmacy,” Lippincott Williams & Wilkins, 2005; and University of the Sciences in Philadelphia (eds.), “Remington: The Principles of Pharmacy Practice,” Lippincott Williams & Wilkins, 2008.[000430] Pharmaceutically acceptable carriers will generally be sterile, at least for human use. A pharmaceutical composition will generally comprise agents for buffering and preservation in storage, and can include buffers and carriers for appropriate delivery, depending on the route of administration. Examples of pharmaceutically acceptable carriers include, without limitation, normal (0.9%) saline, phosphate-buffered saline (PBS), Hank’s balanced salt solution (HBSS), and multiple electrolyte solutions such as PlasmaLyte ATM (Baxter).[000431] Suitable diluents for polypeptides, including antibodies and / or cells include but are not limited to saline solutions, pH buffered solutions and glycerol solutions or other solutions suitable for freezing polypeptides and / or cells.[000432] Suitable diluents for nucleic acids include but are not limited to water and saline solutions.[000433] Pharmaceutical compositions include, without limitation, lyophilized powders or aqueous or non-aqueous sterile injectable solutions or suspensions, which may further contain antioxidants, buffers, bacteriostats and solutes that render the compositions substantially compatible with the tissues or the blood of an intended recipient. Other components that may be present in such compositions include water, surfactants (such as Tween), alcohols, polyols, glycerin and vegetable oils, for example. Exemplary injection solutions and suspensions may be prepared from sterile powders, granules, tablets, orDocket No.: AARV-020-PCT concentrated solutions or suspensions. The composition may be supplied, for example, but not by way of limitation, as a lyophilized powder which is reconstituted with sterile water or saline prior to administration to the patient.[000434] Pharmaceutical compositions may comprise a pharmaceutically acceptable carrier. Suitable pharmaceutically acceptable carriers include essentially chemically inert and nontoxic compositions that do not interfere with the effectiveness of the biological activity of the pharmaceutical composition. Examples of suitable pharmaceutical carriers include, but are not limited to, water, saline solutions, glycerol solutions, ethanol, N-(1(2,3-dioleyloxy)propyl)N, N, N-trimethylammonium chloride (DOTMA), diolesylphosphotidyl-ethanolamine (DOPE), and liposomes. Such compositions should contain a therapeutically effective amount of the compound, optionally with a suitable amount of carrier so as to provide the form for direct administration to the patient. The terms “dose” and “dosage” are used interchangeably herein. A dose refers to the amount of active ingredient given to an individual at each administration. For the present invention, the dose can refer to the concentration of the antibody or associated components, e.g., the amount of therapeutic agent or dosage of radiolabel. The dose will vary depending on a number of factors, including frequency of administration; size and tolerance of the individual; severity of the condition; risk of side effects; the route of administration; and the imaging modality of the detectable label (if present). One of skill in the art will recognize that the dose can be modified depending on the above factors and / or based on therapeutic progress. The term “dosage form” refers to the particular format of the pharmaceutical, and depends on the route of administration. For example, a dosage form can be in a liquid, e.g., a saline solution for injection.VII. Methods of UseA. Methods of Treatment1. Diseases[000435] Provided herein are methods of treating a disease in a subject that comprises administering to the subject an effective amount of a nucleic acid, an antibody or an immunoconjugate of this disclosure. An “effective amount” is an amount sufficient for an antibody or immunoconjugate to accomplish a stated purpose relative to the absence of the compound. The stated purpose may be, for example, killing pathological cells, either in vitro or in vivo, or producing a therapeutic benefit to a subject. An example of an “effective amount” is an amount sufficient to contribute to the treatment, prevention, or reduction of a symptom or symptoms of a disease, which could also be referred to as a “therapeutically effective amount.” A “reduction” of, or “reducing” a symptom means elimination of, or decreasing of the severity or frequency of, the symptom. A “prophylactically effective amount” of a substance (e.g., an antibody) is an amount of that substance, when administered to a subject, will prevent or delayDocket No.: AARV-020-PCT the onset or reoccurrence of a disease, pathology or condition, or its symptoms, or reduce the likelihood of such. An effective amount does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, an effective amount may be administered in one or more administrations. The exact amounts will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20thEdition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins).[000436] For any antibody or ADC described herein, the therapeutically effective amount can be initially estimated or determined using cell culture assays. Target concentrations will be those concentrations of antibody or ADC that are capable of a desired result (e.g., slowing cell growth), as measured using the methods described herein or known in the art. As is well known in the art, therapeutically effective amounts for use in humans can also be determined from animal models. For example, a dose for humans can be formulated to achieve a concentration that has been found to be effective in animals. The dosage in humans can be adjusted by monitoring effectiveness and adjusting the dosage upwards or downwards, as described above. Adjusting the dose to achieve maximal efficacy in humans based on the methods described above and other methods is well within the capabilities of the ordinarily skilled artisan.[000437] In certain embodiments, the antibody comprises at least one paratope that specifically an epitope of B7H3, e.g., an epitope targeted by the B7H3 antibodies (AB2003 and AB2004); and at least one paratope that binds an epitope of EphA2, e.g., targeted by the EphA2 antibodies (AB2001 and AB2002). The paratopes can have the amino acid sequences of the variable regions, or complete light chains, of these antibodies.[000438] Cancers that can be treated include, without limitation, such as: ACC -Adrenocortical Carcinoma; BLCA - Bladder Urothelial Carcinoma; BRCA-Breast Cancer; CESC - Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma; CHOL-cholangiocarcinoma; COAD - Colon Adenocarcinoma; ESCA - Esophageal Carcinoma; GBM -Glioblastoma Multiforme; HNSC - Head and Neck Squamous Cell Carcinoma; KICH- Kidney Chromophobe; KIRC - Kidney Renal Clear Cell Carcinoma; KIRP - Kidney Renal Papillary Cell Carcinoma; LGG- Brain Lower Grade Glioma; LUAD - Lung Adenocarcinoma; LUSC - Lung Squamous Cell Carcinoma; MESO - Mesothelioma; OV - Ovarian Cancer; PAAD - Pancreatic Adenocarcinoma; PRAD - Prostate Adenocarcinoma; READ - Rectum Adenocarcinoma; SARC - Sarcoma; SKCM - Skin Cutaneous Melanoma; STAD - Stomach Adenocarcinoma; Stomach Adenocarcinoma; STES - Stomach and Esophageal carcinoma; TGCT, Testicular Germ CellDocket No.: AARV-020-PCT Tumors; THCA - Thyroid Carcinoma; THYM - Thymoma; LICEC - Uterine Corpus Endometrial Carcinoma; UCS - Uterine Carcinosarcoma; UVM - Uveal Melanoma.[000439] Cancer cells that express both EphA2 and B7H3 are expected to be present in mixed populations in which different cells express each of these biomarkers to a different degree. Without wishing to be limited by theory, bi-specific, ADC antibodies are expected to be more effective against such populations than monospecific ADC antibodies.2. Routes of Administration[000440] Pharmaceutical compositions comprising antibodies of this disclosure can be administered to a subject by any suitable route of administration.[000441] Intravenous administration involves delivering the pharmaceutical composition directly into the bloodstream which facilitates rapid systemic distribution and enables immediate therapeutic action. Intravenous administration can comprise administration of a bolus or can comprise a slow infusion depending on the desired pharmacokinetic profile in the therapeutic indication.[000442] Intraperitoneal administration involves introducing the pharmaceutical composition into the peritoneal cavity. This mode of administration is especially useful for diseases localized within the abdominal region, as it offers direct access to the site of pathology.[000443] The pharmaceutical composition can be administered subcutaneously, that is into the fatty tissue underneath the skin.[000444] In intramuscular administration, a pharmaceutical composition is injected into muscle tissue. In certain cancers, the pharmaceutical composition can be administered directly into the tumor.[000445] For diseases of the central nervous system the composition can be administered intrathecally or intraventricularly, e.g., into the spinal canal or the brain ventricles.3. Treatment Regimen[000446] The treatment regimen for cancers using the antibodies or ADCs of this disclosure is customized to the cancer in the patient. However, exemplary regimens for existing treatments include the following. Between 1 mg and 12 mg of antibody or ADC per kilogram of body weight is administered as a dose. After an initial dose, the drug can be administered about every week for about every three weeks for five or more cycles, e.g., until remission, sufficient reduction of symptoms, complete reduction of symptoms, or until side effects or toxicity become unmanageable or the drug ceases to have therapeutic benefit.Docket No.: AARV-020-PCT B. Methods of Killing Cells[000447] The antibodies and immunoconjugates of this disclosure are useful for killing cells or labeling cells, either in vitro or in vivo. The methods involve contacting the cells with an antibody or immunoconjugate of this disclosure (e.g., by introducing said antibody or immunoconjugate into a subject in need thereof) and allowing the antibodies to bind to the target cells. Effectiveness of killing cells can be a function of ability to kill target cells, but not non-target cells in a mixed population of cells. Ability to kill cells also can be compared with that of a control, e.g., a control antibody, wherein greater ability of the test antibody compared with the control antibody to kill cells indicates that the test antibody is effective in killing those cells.[000448] Contacting cells from cancer cell lines with the compositions disclosed herein, in vitro, is useful for determining toxicity of the composition on the cells.[000449] Contacting cells in vivo with immunoconjugates labeled with a radioisotope is useful in imaging the location of binding and, therefore, the location of a malignant cell. Detection methods include gamma camera imaging, single photon emission coupled tomography (SPECT), and positron emission tomography (PET).C. Methods of Detection[000450] Antibodies of this disclosure are also useful to detect the presence of cells expressing B7H3 and / or EphA2 in a sample or in a subject. The methods involve contacting the sample or providing the subject with an antibody of this disclosure and detecting binding between the antibody and a cell.[000451] Binding can be detected by providing antibodies bearing detectable labels, and detecting the label.[000452] Methods of detection include, without limitation, enzyme-linked immunosorbent assay (ELISA), immunofluorescence (including fluorescent-activated cell sorting (FACS), surface plasmon resonance, microscopy and immunoprecipitation.[000453] In vivo methods of detection include, for example, positron emission tomography (PET), in which antibodies are conjugated with a radioactive isotope; and magnetic resonance imaging (MRI), in which antibodies are conjugated with MRI contrast agents.[000454] Such methods are also useful in the diagnosis of malignancies. The detection of cells expressing one or more members of a Target Combination Set in amounts above control amounts indicates the presence of malignant cells.SEQUENCE LISTING SEQ. ID DescriptionNO.Docket No.: AARV-020-PCT SEQ. ID Location of engineered cys residue in heavy chainNO:1SEQ. ID Location of engineered cys residue in light chainNO:2SEQ. ID Location of engineered cys residue 1 in heavy chain of bis-diabody-Fc NO:3SEQ. ID Location of engineered cys residue 2 in heavy chain if bis-diabody-Fc NO:4SEQ. ID Trastuzumab LCDR1 N30Q variant (RASQDVQTAVA)NO:5SEQ. ID Trastuzumab LCDR1 N30 variant (RASQDVNTAVA)NO:6SEQ. ID Spacer sequence (GGGGS)nNO:7SEQ. ID Spacer sequence (GGGGA)nNO:8SEQ. ID Spacer sequence (GGGGG)nNO:9SEQ. ID Spacer sequence GGGGSGGGGSEPKSSDKTHTNO:10SEQ. ID Spacer sequence GGGGSGGGGSGGGTGNO:11SEQ. ID Spacer sequence GGGGSGGGGSGGGGSGGGGSNO:12SEQ. ID Spacer sequence LEDKTHTKVEPKSSNO:13SEQ. ID Spacer sequence SGSETPGTSESATPESGGGNO:14SEQ. ID Spacer sequence GTTAASGSSGGSSSGANO:15SEQ. ID Spacer sequence GGGGSGGGGGNO:16SEQ. ID Spacer sequence GGGGSGGGGSNO:17Docket No.: AARV-020-PCT SEQ. ID Spacer sequence GGGGSNO:18SEQ. ID AB2003 (B7H3-E1) HCDR1 of heavy chainNO:19SEQ. ID AB2003 (B7H3-E1) HCDR2 of heavy chainNO:20SEQ. ID AB2003 (B7H3-E1) HCDR3 of heavy chainNO:21SEQ. ID AB2003 (B7H3-E1), AB2004 (B7H3-E2) LCDR2 of light chainNO:22SEQ. ID AB2003 (B7H3-E1), AB2004 (B7H3-E2) LCDR3 of light chainNO:23SEQ. ID AB2003 (B7H3-E1) heavy chain variable regionNO:24SEQ. ID AB2003 (B7H3-E1), AB2004 (B7H3-E2) light chain variable region NO:25SEQ. ID AB2003 (B7H3-E1) heavy chainNO:26SEQ. ID AB2003 (B7H3-E1), AB2004 (B7H3-E2) light chain (N30Q variant) (with NO:27 engineered cys residue)SEQ. ID AB2003 (B7H3-E1), AB2004 (B7H3-E2) light chain (N30 variant) (with NO:28 engineered cys residue)SEQ. ID AB2003 (B7H3-E1), AB2004 (B7H3-E2) light chain (N30Q variant) NO:29 (without engineered cys residue)SEQ. ID AB2003 (B7H3-E1), AB2004 (B7H3-E2) light chain (N30 variant) (without NO:30 engineered cys residue)SEQ. ID AB2004 (B7H3-E2) HCDR1 of heavy chainNO:31SEQ. ID AB2004 (B7H3-E2) HCDR2 of heavy chainNO:32SEQ. ID AB2004 (B7H3-E2) HCDR3 of heavy chainNO:33SEQ. ID AB2004 (B7H3-E2) heavy chain variable regionNO:34Docket No.: AARV-020-PCT SEQ. ID AB2004 (B7H3-E2) heavy chainNO:35SEQ. ID AB2001 (EphA2-El) HCDR1 of heavy chainNO:36SEQ. ID AB2001 (EphA2-El) HCDR2 of heavy chain (SIRPYYSHTY) NO:37SEQ. ID AB2001 (EphA2-El) HCDR3 of heavy chainNO:38SEQ. ID AB2001 (EphA2-El), AB2002 (EphA2-E2) LCDR1 of light chain NO:39SEQ. ID AB2001 (EphA2-El), AB2002 (EphA2-E2) LCDR2 of light chain NO:40SEQ. ID AB2001 (EphA2-El) LCDR3 of light chainNO:41SEQ. ID AB2001 (EphA2-El) heavy chain variable regionNO:42SEQ. ID AB2001 (EphA2-El) light chain variable regionNO:43SEQ. ID AB2001 (EphA2-El) heavy chainNO:44SEQ. ID AB2001 (EphA2-El) light chain (with engineered ™ cys residue) NO:45SEQ. ID AB2001 (EphA2-El) light chain (without engineered ™ cys residue) NO:46SEQ. ID AB2002 (EphA2-E2) HCDR1 of heavy chainNO:47SEQ. ID AB2002 (EphA2-E2) HCDR2 of heavy chain (SIDPSPSYTS) NO:48SEQ. ID AB2002 (EphA2-E2) HCDR3 of heavy chainNO:49SEQ. ID AB2002 (EphA2-E2) LCDR3 of light chainNO:50SEQ. ID AB2002 (EphA2-E2) heavy chain variable regionNO:51Docket No.: AARV-020-PCT SEQ. ID AB2002 (EphA2-E2) light chain variable regionNO:52SEQ. ID AB2002 (EphA2-E2) heavy chainNO:53SEQ. ID AB2002 (EphA2-E2) light chain (with engineered ™ cys residue) NO:54SEQ. ID AB2002 (EphA2-E2) light chain (without engineered ™ cys residue) NO:55SEQ. ID AB2024 heavy chain 2 knob (bis-diabody-Fc; B7H3-El / EphA2-El) NO:56SEQ. ID AB2024 heavy chain 2 hole (bis-diabody-Fc; EphA2-El / B7H3-El) NO:57SEQ. ID AB2032 heavy chain 2 knob (bis-diabody-Fc; B7H3-El / EphA2-E2) NO:58SEQ. ID AB2032 heavy chain 2 hole (bis-diabody-Fc; EphA2-E2 / B7H3-El) NO:59SEQ. ID AB2006 heavy chain (MUTTA™2 diabody-Fab-Fc B7H3-El / EphA2-El) NO:60SEQ. ID AB2007 heavy chain (MUTTA™2 diabody-Fab-Fc B7H3-El / EphA2-E2) NO:61SEQ. ID AB2008 heavy chain (MUTTA™2 diabody-Fab-Fc B7H3-E2 / EphA2-E2) NO:62SEQ. ID AB2009 heavy chain (MUTTA™2 diabody-Fab-Fc B7H3-E2 / EphA2-El) NO:63SEQ. ID AB2010 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-El / B7H3-E2) NO:64SEQ. ID AB2011 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-E2 / EphA2-El) NO:65SEQ. ID AB2012 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-E2 / B7H3-El) NO:66SEQ. ID AB2013 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-El / B7H3-E2) NO:67SEQ. ID AB2015 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-El / B7H3-El) NO:68Docket No.: AARV-020-PCT SEQ. ID AB2016 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-El / EphA2-E2) NO:69SEQ. ID AB2017 heavy chain (MUTTA™2 diabody-Fab-Fc B7H3-El / EphA2-El) NO:70SEQ. ID AB2018 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-El / B7H3-El) NO:71SEQ. ID AB2021 heavy chain 1 knob (MUTTA™2 diabody-Fab-Fc EphA2-El / B7H3- NO:72 El)SEQ. ID AB2021 heavy chain 2 hole (MUTTA™2 diabody-Fab-Fc EphA2-El / B7H3- NO:73 E2)SEQ. ID AB2022 heavy chain 1 knob (MUTTA™2 diabody-Fab-Fc EphA2-E2 / B7H3- NO:74 El)SEQ. ID AB2022 heavy chain 2 hole (MUTTA™2 diabody-Fab-Fc EphA2-El / B7H3- NO:75 E2)SEQ. ID AB2023 heavy chain (MUTTA™2 diabody-Fab-Fc B7H3-E1 / B7H3-E2) NO:76SEQ. ID AB2027 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-E2b / B7H3-El) NO:77SEQ. ID AB2028 heavy chain (MUTTA™2 diabody-Fab-Fc B7H3-El / EphA2-E2) NO:78SEQ. ID AB2029 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-E2 / B7H3-El) NO:79SEQ. ID AB2033 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-E2 / B7H3-E2) NQ:80SEQ. ID AB2034 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-E2 / B7H3-El) NO:81SEQ. ID AB2019 heavy chain (MUTTA™4 diabody-Fab-Fc B7H3-El / EphA2-El) NO:82SEQ. ID AB2020 heavy chain (MUTTA™4 Fab-Diabody-Fc EphA2-El / B7H3-El) NO:83SEQ. ID AB2025 heavy chain (MUTTA™4 Fab-Diabody-Fc B7H3-El / EphA2-E2) NO:84SEQ. ID AB2026 heavy chain (MUTTA™4 Fab-Diabody-Fc EphA2-E2 / B7H3-El) NO:85Docket No.: AARV-020-PCT SEQ. ID AB2030 heavy chain (MUTTA™4 Fab-Diabody-Fc B7H3-El / EphA2-E2) NO:86SEQ. ID AB2031 heavy chain (MUTTA™4 Fab-Diabody-Fc EphA2-E2 / B7H3-El) NO:87SEQ. ID AB2035 heavy chain (MUTTA™4 Fab-Diabody-Fc EphA2-E2 / B7H3-E2) NO:88SEQ. ID AB2036 heavy chain (MUTTA™4 Fab-Diabody-Fc B7H3-E2 / EphA2-E2) NO:89SEQ. ID AB2037 heavy chain (MUTTA™4 Fab-Diabody-Fc EphA2-E2 / B7H3-E2) NQ:90SEQ. ID AB2038 heavy chain (MUTTA™4 Fab-Diabody-Fc B7H3-E2 / EphA2-E2) NO:91SEQ. ID AB2001 (EphA2-El) HCDR2 of heavy chain (SIRPYYSHTYY)NO:92SEQ. ID AB2002 (EphA2-E2) HCDR2 of heavy chain (SIDPSPSYTSY)NO:93SEQ. ID LALA-PS motif part 1 (CPAPEAAGGPSV)NO:94SEQ. ID LALA-PS motif part 2 ( KALPASIEKTIS )NO:95SEQ. ID AB2041 heavy chain (MUTTA™2 diabody-Fab-Fc EphA2-E2b / B7H3-El) NO:96SEQ. ID AB2039 heavy chain (MUTTA™4 Fab-Diabody-Fc B7H3-El / EphA2-E2b) NO:97SEQ. ID AB2040 heavy chain (MUTTA™4 Fab-Diabody-Fc B7H3-El / EphA2-E2b) NO:98EXEMPLARY EMBODIMENTS[000455] 1. An antibody comprising a first paratope and a second paratope, wherein one of the paratopes specifically binds to B7H3 and another of the paratopes specifically binds to EphA2.[000456] 2. The antibody of embodiment 1, wherein the paratopes comprise a variable light chain region and a variable heavy chain region selected from antibodies AB2001, AB2002, AB2003, and AB2004.Docket No.: AARV-020-PCT [000457] 3. The antibody of embodiment 1, wherein the paratopes comprise a variable light chain and a variable heavy chain portion selected from antibodies AB2001, AB2002, AB2003, and AB2004.[000458] 4. The antibody of embodiment 1, comprising an intact, tetrameric antibody or an antigen-binding fragment thereof.[000459] 5. The antibody of embodiment 1, wherein either or both of the first and second paratopes comprises a fragment antigen binding (Fab), a fragment antigen-binding 2 (F(ab’)2), a single chain Fab (scFab), a single chain variable fragment (scFv), a diabody, a single domain antibody (sdAb) or a nanobody (“VHH antibody”).[000460] 6. The antibody of embodiment 1, wherein at least one of the paratopes is a scFv comprising a variable heavy chain (VH)-spacer-variable light chain (VL) or a VL-spacer-VH orientation.[000461] 7. The antibody of any one of embodiments 1-6, wherein a paratope that binds B7H3 comprises complementarity determining regions:HCDR1: GFTINAYRMH (SEQ. ID NO:19)HCDR2: YIYPNSAYTIY (SEQ. ID NO:20)HCDR3: NLRPFFALDY (SEQ. ID NO:21)LCDR1: RASQDVQTAVA (SEQ. ID NO:5)LCDR2: SASFLYS (SEQ. ID NO:22)LCDR3: QQHYTTPPT (SEQ. ID NO:23)[000462] 8. The antibody of any one of embodiments 1-6, wherein a paratope that binds B7H3 comprises complementarity determining regions:HCDR1: GFTIKSNYIH (SEQ. ID NO:31)HCDR2: MIYPTIGNTRY (SEQ. ID NO:32)HCDR3: GVGNDFRALDY (SEQ. ID NO:33)LCDR1: RASQDVQTAVA (SEQ. ID NO:5)LCDR2: SASFLYS (SEQ. ID NO:22)LCDR3: QQHYTTPPT (SEQ. ID NO:23).[000463] 9. The antibody of any one of embodiments 1-8, wherein a paratope that binds EphA2 comprises complementarity determining regions:HCDR1: GFTIYNSSIH (SEQ. ID NO:36)HCDR2: SIRPYYSHTYY (SEQ. ID NO:92)HCDR3: YYAMDY (SEQ. ID NO:38)LCDR1: RASQSVSSAVA (SEQ. ID NO:39)LCDR2: SASSLYS (SEQ. ID NO:40)Docket No.: AARV-020-PCT LCDR3: QQYYGYGGYPIT (SEQ. ID NO:41)[000464] 10. The antibody of any one of embodiments 1-8, wherein a paratope that binds EphA2 comprises complementarity determining regions:HCDR1: GFTLYYYPMH (SEQ. ID NO:47)HCDR2: SIDPSPSYTSY (SEQ. ID NO:93)HCDR3: SAPSADFGLDY (SEQ. ID NO:49)LCDR1: RASQSVSSAVA (SEQ. ID NO:39)LCDR2: SASSLYS (SEQ. ID NO:40)LCDR3: QQWAYGPFT (SEQ. ID NO:50)[000465] 11. The antibody of any one of embodiments 7-10, wherein the paratope that specifically binds B7H3 comprises:a) a heavy chain variable region sequence SEQ. ID NO:24; andb) a light chain variable region sequence SEQ. ID NO:25.[000466] 12. The antibody of any one of embodiments 7-10, wherein the paratope that specifically binds B7H3 comprises:a) a heavy chain variable region sequence SEQ. ID NO:34; andb) a light chain variable region sequence SEQ. ID NO:25.[000467] 13. The antibody of any one of embodiments 7-12, wherein the paratope that specifically binds EphA2 comprises:a) a heavy chain variable region sequence (SEQ. ID NO:42); andb) a light chain variable region sequence (SEQ. ID NO:43).[000468] 14. The antibody of any one of embodiments 7-12, wherein the paratope that specifically binds EphA2 comprises:a) a heavy chain variable region sequence (SEQ. ID NO:51); andb) a light chain variable region sequence (SEQ. ID NO:52).[000469] 15. The antibody of any one of embodiments 7-15, comprising:a) a heavy chain portion and light chain of AB2001;b) a heavy chain portion and light chain of AB2002;c) a heavy chain portion and light chain of AB2003;d) a heavy chain portion and light chain of AB2004; ore) a functional equivalent thereof having at least 90%, at least 95%, at least 97%, at least 98% or at least 99% sequence identity thereto.[000470] 16. The antibody of any one of embodiments 7-15, wherein the antibody is a monoclonal antibody.Docket No.: AARV-020-PCT [000471] 17. The antibody of embodiment 16, wherein the antibody is bi-specific and bivalent.[000472] 18. The antibody of embodiment 17, comprising:a) a first paratope comprised in an Fab;b) a second paratope comprised in an Fab; andc) an Fc region configured as a knob-into-hole.[000473] 19. The antibody of embodiment 17, comprising:a) a first paratope comprised in an Fab;b) a second paratope comprised in an scFv; andc) an Fc region configured as a knob-into-hole.[000474] 20. The antibody of embodiment 17, comprising:a) a first paratope and a second paratope comprised in a diabody; andb) an Fc region configured as a knob-into-hole.[000475] 21. The antibody of embodiment 1, which is bi-specific and trivalent.[000476] 22. The antibody of embodiment 21, comprising two paratopes that specifically bind B7H3 and one paratope that specifically binds EphA2.[000477] 23. The antibody of embodiment 21, comprising two paratopes that specifically bind EphA2 and one paratope that specifically binds B7H3.[000478] 24. The antibody of embodiment 21, comprising:a) a first light chain comprising, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) a first heavy chain comprising, from N-terminus to C-terminus:(i) a first heavy chain portion comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;(ii) a first diabody region comprising a second VHregion and a second VL region, in either order; and(iii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region comprising a knob or a hole;c) the second heavy chain comprising, from N-terminus to C-terminus:(i) a second diabody region comprising a third H region and a third L region, in either order; and(iii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region comprising a hole or a knob, respectively;wherein:the two heavy chains are associated by a knob-into-hole arrangement;Docket No.: AARV-020-PCT the first light chain and the first heavy chain portion form a first Fab region comprising a first paratope;the first and second diabody regions form a diabody having a second paratope comprising the third VLregion and the second VH region, and a third paratope comprising the second VLregion and the third VH region.[000479] 25. The antibody of embodiment 21, comprising:a) first heavy chain comprising from N-terminus to C-terminus:i) a bivalent first paratope, Fab+Fab; andii) an Fc region with a knob or hole; andb) second heavy chain comprising from N-terminus to C-terminus:i) a monovalent second paratope as an scFvii) an Fc region with a hole or knob, respectively.[000480] 26. The antibody of embodiment 1, wherein the antibody is bi-specific and tetravalent.[000481] 27. The antibody of embodiment 26, comprising two paratopes that specifically bind B7H3 and two paratopes that specifically bind EphA2.[000482] 28. The antibody of embodiment 26, comprising three paratopes that specifically bind B7H3 and one paratope that specifically binds EphA2.[000483] 29. The antibody of embodiment 26, comprising three paratopes that specifically bind EphA2 and one paratope that specifically binds B7H3.[000484] 30. The antibody of embodiment 26, wherein the paratopes that specifically bind B7H3 are located at NW and NE positions, and the paratopes that specifically bind EphA2 are located at SW and SE positions.[000485] 31. The antibody of embodiment 26, wherein the paratopes that specifically bind EphA2 are located at NW and NE positions, and the paratopes that specifically bind B7H3 are located at SW and SE positions.[000486] 32. The antibody of embodiment 26, wherein:a) at least two paratopes are comprised in Fab regions;b) at least two paratopes are comprised in scFvs; orc) at least two paratopes are comprised in diabodies.[000487] 33. The antibody of embodiment 26, comprising first and second light chains and first and second heavy chains, wherein:a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;Docket No.: AARV-020-PCT b) the second light chain comprises, from N-terminus to C-terminus, a second VLregion and a second CL region;wherein the first and second light chains comprise the same amino acid sequence; c) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first heavy chain portion comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;(ii) a first diabody region comprising a second VHregion and a third VLregion, in either order; and(iii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region;d) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second heavy chain portion comprising a third VH region and a second CH1 region; (ii) a second diabody region comprising a fourth VH region and a fourth L region, in either order; and(iii) a second Fc region comprising a second CH2 region and a second CH3 region; wherein the first and second heavy chains comprise the same amino acid sequence; andwherein:the two heavy chains are associated;the first and second diabody regions form a diabody having a first paratope comprising the fourth VLregion and the second H region, and a second paratope comprising the third VL region and the fourth VHregion;the first light chain and the first heavy chain portion form a first Fab region comprising a third paratope; andthe second light chain and the second heavy chain portion form a second Fab region comprising a fourth paratope.[000488] 34. The antibody of embodiment 26, comprising first and second light chains and first and second heavy chains, wherein:a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VL region and a second CL region;wherein the first and second light chains comprise the same amino acid sequence; c) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first diabody region comprising a first heavy chain variable (VH) region and a third VL region, in either order; andDocket No.: AARV-020-PCT (ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a first heavy chain portion comprising a second VH region and a first heavy chain constant 1 (CH1) region;d) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second diabody region comprising a third VHregion and a fourth VL region, in either order; and(ii) a second Fc region comprising a second CH2 region and a second CH3 region; and (iii) a second heavy chain portion comprising a fourth VH region and a second CH1 region;wherein the first and second heavy chains comprise the same amino acid sequence; wherein:the two heavy chains are linked;the first and second diabody regions form a diabody having a first paratope comprising the fourth VL region and the first H region, and a second paratope comprising the third VL region and the third VH region;the first light chain and the first heavy chain portion form a first Fab region comprising a third paratope; andthe second light chain and the second heavy chain portion form a second Fab region comprising a fourth paratope.[000489] 35. The antibody of embodiment 26, comprising first and second light chains and first and second heavy chains, wherein:a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VLregion and a second CL region;wherein the first and second light chains comprise the same amino acid sequence; c) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first heavy chain portion comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a first scFV region comprising a second VH region and a third VL region, in either order; andd) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second heavy chain portion comprising a third VHregion and a second CH1 region; (ii) a second Fc region comprising a second CH2 region and a second CH3 region;Docket No.: AARV-020-PCT (iii) a second scFV region comprising a fourth VHregion and a fourth VL region, in either order; andwherein the first and second heavy chains comprise the same amino acid sequence; wherein:the two heavy chains are associated;the second VH region and a third VL region of the first scFv region assemble into a first paratope;the fourth H region and a fourth VL region of the second scFv region assemble into a second paratope;the first light chain and the first heavy chain portion form a first Fab region comprising a third paratope; andthe second light chain and the second heavy chain portion form a second Fab region comprising a fourth paratope.[000490] 36. The antibody of embodiment 26, comprising first and second light chains and first and second heavy chains, wherein:a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VLregion and a second CL region;wherein the first and second light chains comprise the same amino acid sequence; c) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first heavy chain portion comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a second heavy chain portion comprising a second heavy chain variable (VH) region and a second heavy chain constant 1 (CH1) region;d) the second heavy chain comprises, from N-terminus to C-terminus:(i) a first scFV region comprising a third VL region and a third VH region;(ii) a second Fc region comprising a second CH2 region and a second CH3 region; (iii) a second scFV region comprising a fourth VH region and a fourth VL region; wherein:the two heavy chains are associated;the first light chain and the first heavy chain portion form a first Fab region comprising a first paratope;the second light chain and the second heavy chain portion form a second Fab region comprising a second paratope;Docket No.: AARV-020-PCT the third VHregion and a third VL region of the first scFv region form a third paratope; andthe fourth VHregion and a fourth VL region of the second scFv region form a fourth paratope.[000491] 37. The antibody of embodiment 26, comprising first and second heavy chains, wherein:a) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first diabody region comprising a first heavy chain variable ( H) region and a first L region, in either order;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a second diabody region comprising a second heavy chain variable (VH) region and a second VL region, in either order;d) the second heavy chain comprises, from N-terminus to C-terminus:(i) a third diabody region comprising a third heavy chain variable (VH) region and a third VL region, in either order;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a fourth diabody region comprising a fourth heavy chain variable (VH) region and a fourth VLregion, in either order;wherein the first and second heavy chains comprise the same amino acid sequence; wherein:the two heavy chains are associated;the first and third diabody regions form a diabody having a first paratope comprising the first VLregion and the third VH region, and a second paratope comprising the third VL region and the first VH region;the second and fourth diabody regions form a diabody having a third paratope comprising the fourth VL region and the second VH region, and a fourth paratope comprising the second VL region and the fourth VH region.[000492] 38. The antibody of embodiment 26, comprising first and second heavy chains, wherein:a) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first diabody region comprising a first heavy chain variable (VH) region and a first VL region, in either order;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a first scFV region comprising a second VLregion and a second VH region;Docket No.: AARV-020-PCT b) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second diabody region comprising a third heavy chain variable (VH) region and a third VLregion, in either order;(ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a second scFV region comprising a fourth VH region and a fourth VL region; wherein the first and second heavy chains comprise the same amino acid sequence; wherein:the two heavy chains are associated;the first and second diabody regions form a diabody having a first paratope comprising the first VL region and the third H region, and a second paratope comprising the third VL region and the first VH region;the second VH region and the second VL region of the first scFv region form a third paratope; andthe fourth VH region and a fourth VL region of the second scFv region form a fourth paratope.[000493] 39. The antibody of embodiment 26, comprising first and second heavy chains, wherein:a) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first scFV region comprising a first VLregion and a first VHregion;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a first diabody region comprising a second heavy chain variable (VH) region and a second VLregion, in either order;d) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second scFV region comprising a third VH region and a third VL region;(ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a second diabody region comprising a fourth heavy chain variable (VH) region and a fourth VL region, in either order;wherein the first and second heavy chains comprise the same amino acid sequence; andwherein:the two heavy chains are associated;the first VHregion and the first VL region of the first scFv region form a first paratope; the third VHregion and a third VL region of the second scFv region form a second paratope; andDocket No.: AARV-020-PCT the first and second diabody regions form a diabody having a third paratope comprising the fourth VLregion and the second VH region, and a fourth paratope comprising the second VL region and the fourth VHregion.[000494] 40. The antibody of embodiment 26, comprising first and second heavy chains, wherein:a) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first scFV region comprising a first VLregion and a first VHregion;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a second scFV region comprising a second VL region and a second H region; b) the second heavy chain comprises, from N-terminus to C-terminus:(i) a third scFV region comprising a third VH region and a third VL region;(ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a fourth scFV region comprising a fourth VL region and a fourth VH region; wherein the first and second heavy chains comprise the same amino acid sequence; andwherein:the two heavy chains are associated;the first VHregion and the first VL region of the first scFv region form a first paratope; the second VH region and the second VL region of the second scFv region form a first paratope;the third VHregion and a third VL region of the third scFv region form a third paratope. the fourth VHregion and the fourth VL region of the fourth scFv region form a first paratope.[000495] 41. The antibody of embodiment 26, comprising first and second light chains and first and second heavy chains, wherein:a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VL region and a second CL region;wherein the first and second light chains comprise the same amino acid sequence; c) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first heavy chain portion comprising a first heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; andDocket No.: AARV-020-PCT (iii) a first diabody region comprising a second VHregion and a third VL region, in either order; andd) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second heavy chain portion comprising a third heavy chain variable (VH) region and a second heavy chain constant 1 (CH1) region;(ii) a second Fc region comprising a second heavy chain constant 2 (CH2) region and a second heavy chain constant 3 (CH3) region; and(iii) a second diabody region comprising a fourth VH region and a fourth VL region, in either order;wherein the first and second heavy chains comprise the same amino acid sequence and wherein:the two heavy chains are associated;the first and second diabody regions form a diabody having a first paratope comprising the third L region and the fourth VH region, and a second paratope comprising the fourth VL region and the second VH region;the first light chain and the first heavy chain portion form a first Fab region comprising a third paratope; andthe second light chain and the second heavy chain portion form a second Fab region comprising a fourth paratope.[000496] 42. The antibody of embodiment 26, comprising first and second light chains and first and second heavy chains, wherein:a) the first light chain comprises, from N-terminus to C-terminus, a first light chain variable (VL) region and a first light chain constant (CL) region;b) the second light chain comprises, from N-terminus to C-terminus, a second VLregion and a second CL region;wherein the first and second light chains comprise the same amino acid sequence; c) the first heavy chain comprises, from N-terminus to C-terminus:(i) a first scFV region comprising a third VL region and a first VH region;(ii) a first Fc region comprising a first heavy chain constant 2 (CH2) region and a first heavy chain constant 3 (CH3) region; and(iii) a first heavy chain portion comprising a second heavy chain variable (VH) region and a first heavy chain constant 1 (CH1) region;d) the second heavy chain comprises, from N-terminus to C-terminus:(i) a second heavy chain portion comprising a third heavy chain variable (VH) region and a second heavy chain constant 1 (CH1) region;(ii) a second Fc region comprising a second CH2 region and a second CH3 region;(iii) a second scFV region comprising a fourth VHregion and a fourth VL region;Docket No.: AARV-020-PCT wherein:the two heavy chains are associated;the first light chain and the first heavy chain portion form a first Fab region comprising a first paratope;the second light chain and the second heavy chain portion form a second Fab region comprising a second paratope;the first VHregion and the third VLregion of the first scFv region form a third paratope; andthe fourth VH region and a fourth VL region of the second scFv region form a fourth paratope.[000497] 43. The antibody of embodiment 26, comprising first and second light chains comprising the same amino acid sequence, and first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus:a) a first pair of paratopes comprised in Fab regions;b) a second pair of paratopes, comprised in a diabody; andc) an Fc region.[000498] 44. The antibody of embodiment 26, comprising first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus:a) a first pair of paratopes comprised in a diabody.b) an Fc region; anda) a second pair of paratopes comprised in Fab regions;[000499] 45. The antibody of embodiment 26, comprising first and second light chains comprising the same amino acid sequence, and first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus:a) a first pair of paratopes comprised in Fab regions;b) an Fc region; andc) a second pair of paratopes, each comprised in an scFv region.[000500] 46. The antibody of embodiment 26, comprising first and second light chains comprising the same amino acid sequence, and first and second heavy chains comprising different amino acid sequences, and comprising, from N-terminus to C-terminus:a) a first pair of paratopes, one paratope comprised in an Fab region and one paratope comprised in an scFv region;b) an Fc region; andc) a second pair of paratopes, one paratope comprised in an Fab region and one paratope comprised in an scFv region;Docket No.: AARV-020-PCT wherein one of the heavy chains comprises two VH regions and two VL regions forming the scFv regions.[000501] 47. The antibody of embodiment 26, comprising first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus:a) a first pair of paratopes comprised within a diabody;b) an Fc region; andc) a second pair of paratopes comprised within a diabody.[000502] 48. The antibody of embodiment 26, comprising first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus:a) a first pair of paratopes comprised within a diabody;b) an Fc region; andc) a second pair of paratopes, each comprised in an scFv region.[000503] 49. The antibody of embodiment 26, comprising first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus:a) a first pair of paratopes, each comprised in an scFv region;b) an Fc region; andc) a second pair of paratopes comprised within a diabody.[000504] 50. The antibody of embodiment 26, comprising first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus:a) a first pair of paratopes, each comprised as an scFv region;b) an Fc region; andc) a second pair of paratopes, each comprised as an scFv region.[000505] 51. The antibody of embodiment 26, comprising first and second light chains comprising the same amino acid sequence, and first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus:a) a first pair of paratopes comprised in Fab regions;b) an Fc region; andc) a second pair of paratopes, comprised as a diabody.[000506] 52. The antibody of embodiment 26, comprising first and second light chains comprising the same amino acid sequence, and first and second heavy chains comprising the same amino acid sequence, and comprising, from N-terminus to C-terminus:Docket No.: AARV-020-PCT a) a first pair of paratopes, one comprised in an Fab region and one comprised in an scFv region;b) an Fc region; andc) a second pair of paratopes, one comprised in an scFv region and one comprised in an Fab region.[000507] 53. The antibody of embodiment 26, wherein all of the light chain variable regions have the same amino acid sequence.[000508] 54. The antibody of embodiment 1, which is tri-specific and tetravalent.[000509] 55. The antibody of embodiment 54, comprising two paratopes that bind the same epitope of EphA2, one paratope that binds a first epitope of B7H3, and one paratope that binds a second epitope of B7H3.[000510] 56. The antibody of embodiment 54, comprising two paratopes that bind the same epitope of B7H3, one paratope that binds a first epitope of EphA2, and one paratope that binds a second epitope of EphA2.[000511] 57. The antibody of embodiment 1, which is tetra-specific and tetravalent.[000512] 58. The antibody of embodiment 57, comprising one paratope that binds a first epitope of B7H3, one paratope that binds a second epitope of B7H3, one paratope that binds a first epitope of EphA2, and one paratope that binds a second epitope of EphA2.[000513] 59. The antibody of any of embodiments 1-58, further comprising one or more payloads conjugated thereto.[000514] 60. The antibody of embodiment 59, wherein at least one payload is selected from the group consisting of: a drug, a radionucleotide, a fluorophore, biotin, RNA, an antibiotic, a protein and a detectable moiety.[000515] 61. The antibody of embodiment 59, wherein at least one of the payloads is selected from maytansinoid, DM-1, DM-4, auristatin, monomethyl auristatin E, monomethyl auristatin F, dolastatin, tubulysin, eribulin, cryptophycin, benzodiazepine, indolino-benzodiazepine, isoquinolidino-benzodiazepine, pyrrolo-benzodiazepine, alpha-amanitin, trichothene, camptothecin derivatives (SN-38, exatecan, belotecan, DXd, topotecan, samrotecan), duocarmycin, DGN549, CC1065, calicheamicin, N-acetyl calicheamicin.an enediyne antibiotic, taxane, doxorubicin derivatives, anthracycline and stereoisomers, azanofide, isosteres, and analogs, hetero dimer or homo dimers or derivatives thereof.[000516] 62. The antibody of embodiment 59, wherein at least one payload is attached to the antibody via a cleavable (enzymatic or non-enzymatic) or non-cleavable or traceless linker.Docket No.: AARV-020-PCT [000517] 63. The antibody of embodiment 62, wherein at least one of the linkers is conjugated through:a) a reduced disulfide bond in the antibody; orb) an amino acid residue (e.g., cysteine or lysine) naturally present or introduced into an amino acid sequence of the antibody.[000518] 64. The antibody of embodiment 63, comprising amino acid substitutions: (a) HC-A118C and LC-V205C; and / or(b) HC-S156C, HC-S239C, and HC-V266C (EU numbering).[000519] 65. The antibody of embodiment 63, wherein at least one of the linkers is conjugated through a non-natural amino acid, disulfide re-bridging, a peptide tag, glycan modification, or an enzymatic modification method used to generate site-specific immunoconjugates.[000520] 66. The antibody or immunoconjugate of any of embodiment 26, wherein the antibody comprises:a) a diabody region optionally attached to an Fc region through Spacer 1, and the Fc region attached to the heavy chain portion through a Spacer 2;b) a heavy chain portion optionally attached through Spacer 3 to a diabody region, and the diabody region optionally attached through a Spacer 4 to an Fc region;c) an Fc region attached to a heavy chain portion through a Spacer 5; ord) a heavy chain attached to another heavy chain portion through a Spacer 6.[000521] 67. The antibody or immunoconjugate of embodiment 66, wherein Spacers 1-6 independently comprise between 5 and 50 amino acids.[000522] 68. The antibody or immunoconjugate of embodiment 67, wherein Spacers 1-6 are independently selected from a monomer or polymer of the sequence (GGGGS)n (SEQ. ID NO:7), (GGGGA)n (SEQ. ID NO:8) or (GGGGG)n (SEQ. ID NO:9), wherein n is any of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.[000523] 69. The antibody or immunoconjugate of embodiment 66, wherein Spacers 1-6 are independently selected from GGGGSGGGGSEPKSSDKTHT (SEQ. ID NO:10), GGGSGGGSGGGSGGGSGSTG (SEQ. ID NO:11), LEDKTHTKVEPKSS (SEQ. ID NO:13), SGSETPGTSESATPESGGG (SEQ. ID NO:14), and GTTAASGSSGGSSSGA (SEQ. ID NO:15).[000524] 70. The antibody or immunoconjugate of embodiment 66, comprising a diabody region optionally attached to an Fc region through Spacer 1, and the Fc region attached to the heavy chain portion through Spacer 2; wherein Spacer 1 and Spacer 2, if present, are selected from the following pairs:Spacer 1 - Diabody-Fc Spacer 2 - Fc-FabDocket No.: AARV-020-PCT 0-4 amino acids 0-4 amino acidsAbout 10 amino acids About 20 amino acids About 10 amino acids About 10 amino acids About 10 amino acids About 5 amino acidsAbout 10 amino acids 0-4 amino acidsAbout 5 amino acids About 20 amino acids About 5 amino acids 0-4 amino acids0-4 amino acids About 20 amino acids 0-4 amino acids 0-4 amino acidsAbout 10 amino acids About 20 amino acids[000525] 71. The antibody or immunoconjugate of embodiment 70, wherein Spacer 1 and Spacer 2, if present, are selected from the following pairs:Spacer 1 - Diabody-Fc Spacer 2 - Fc-Fab(G4S)0 (no spacer) (G4S)0 (no spacer)(G4S)2 (G4S)4(G4S)2 (G4S)2(G4S)2 (G4S)1(G4S)2 (G4S)0(G4S)1 (G4S)4(G4S)1 (G4S)0(G4S)0 (G4S)4(G4S)0 (G4S)0(G4S)2 (G4S)4[000526] 72. The antibody or immunoconjugate of embodiment 66, comprising (i) a heavy chain portion optionally attached through Spacer 3 to a diabody region, and the diabody region optionally attached through Spacer 4 to an Fc region, wherein Spacer 3 and Spacer 4, if present, are selected from the following pairs:Spacer 3 - Fab-Diabody Spacer 4 - Diabody-Fc 0-4 amino acids 0-4 amino acidsAbout 20 amino acids About 10 amino acids About 5 amino acids About 10 amino acids About 20 amino acids 0-4 amino acidsAbout 15 amino acids About 10 amino acidsDocket No.: AARV-020-PCT About 10 amino acids About 10 amino acids About 5 amino acids About 10 amino acids 0-4 amino acids About 10 amino acids 0-4 amino acids About 5 amino acids[000527] 73. The antibody or immunoconjugate of embodiment 72, wherein Spacer 3 and Spacer 4, if present, are selected from the following pairs:Spacer 3 - Fab-Diabody Spacer 4 - Diabody-Fc 0-4 amino acids 0-4 amino acidsAbout 20 amino acids About 10 amino acids About 5 amino acids About 10 amino acids About 20 amino acids 0-4 amino acidsAbout 15 amino acids About 10 amino acids About 10 amino acids About 10 amino acids About 5 amino acids About 10 amino acids 0-4 amino acids About 10 amino acids 0-4 amino acids About 5 amino acids[000528] 74. An antibody comprising amino acid sequences of any of antibodies AB2003, AB2004, AB2006, AB2007, AB2008, AB2009, AB2010, AB2011, AB2012, AB2013, AB2014, AB2015, AB2016, AB2017, AB2018, AB2019, AB2020, AB2021, AB2022, AB2023, and AB2025.[000529] 75. The antibody of any of embodiments 1-74, further comprising one or more payloads conjugated thereto.[000530] 76. A method of making an immunoconjugate comprising:a) providing an antibody of any of embodiments 1-75; andb) conjugating one or more payloads to the antibody.[000531] 77. The method of embodiment 76, wherein at least one of the payloads is conjugated to the antibody through a linker.[000532] 78. The method of embodiment 76, wherein at least one of the payloads is conjugated to the antibody through a broken disulfide bond.[000533] 79. The method of embodiment 76, wherein the antibody is a cysteinesubstituted antibody, and at least one payload is coupled to the antibody through a substituted cysteine.Docket No.: AARV-020-PCT [000534] 80. The method of embodiment 76, wherein the immunoconjugate has a drug-antibody ratio (“DAR”) of at least any of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12.[000535] 81. A collection of one or more nucleic acid molecules that collectively encode paratopes that bind B7H3 and EphA2.[000536] 82. The collection of nucleic acid molecules of embodiment 81, encoding one or more antibodies of any of embodiments 1-75.[000537] 83. The collection of nucleic acid molecules of e...

Claims

Docket No.: AARV-020-PCT WHAT IS CLAIMED IS:

1. A multi-specific, tetravalent antibody in a diabody-Fc-Fab format that specifically binds either B7H3 and EphA2, comprising two heavy chains and two light chains, wherein the light chains comprise, from N-terminus to C-terminus, a light chain variable region (VL) and light chain constant (CL) region; and the heavy chains comprise, from N-terminus to C-terminus, (1) a diabody region comprising heavy chain variable region (VH) and light chain variable region (VL), in either order, (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region; wherein the diabody regions are associated to form a diabody comprising first and second paratopes, the CH2 and CH3 regions are associated to form an Fc domain, and the light chains and the heavy chain regions are associated to form Fab regions comprising third and fourth paratopes, and wherein each paratope specifically binds either B7H3 or EphA2, and the paratopes, collectively, specifically bind both B7H3 and EphA2.

2. The antibody of claim 1, wherein the first and second paratopes specifically bind B7H3, and the third and fourth paratopes specifically bind EphA2.

3. The antibody of claim 2, wherein the first and second paratopes specifically bind the same epitope of B7H3, and the third and fourth paratopes specifically bind the same epitope of EphA2.

4. The antibody of claim 2, wherein the first and second paratopes specifically bind different epitopes of B7H3, and / or the third and fourth paratopes specifically bind different epitopes of EphA2.

5. The antibody of claim 1, wherein the first and second paratopes specifically bind EphA2, and the third and fourth paratopes specifically bind B7H3.

6. The antibody of claim 5, wherein the first and second paratopes specifically bind the same epitope of EphA2, and the third and fourth paratopes specifically bind the same epitope of B7H3.

7. The antibody of any of claims 1 to 6, wherein the antibodies comprise one or more CDR sequence sets of an antibody selected from: AB2001, AB2002, AB2003, AB2004 and AB2039.

8. The antibody of any of claims 1 to 7, wherein the antibody comprises one or more of: a heavy chain variable region, a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region, a light chain variable region, a light chainDocket No.: AARV-020-PCT or a diabody region, of an antibody selected from: AB2006, AB2007, AB2008, AB2010, AB2012, AB2013, AB2015, AB2017, AB2018, AB2021, AB2022, AB2027, AB2028, AB2029, AB2033, AB2034, and AB2041.

9. The antibody of any of claims 1 to 8, having amino acid sequences at least 90% identical to, at least 95% identical to, at least 98% identical to, at least 99% identical to, or identical to any of AB2006, AB2007, AB2008, AB2010, AB2012, AB2013, AB2015, AB2017, AB2018, AB2021, AB2022, AB2027, AB2028, AB2029, AB2033, AB2034, and AB2041.

10. A multi-specific, tetravalent antibody in an Fab-diabody-Fc format that specifically binds B7H3 and EphA2,comprising two heavy chains and two light chains, wherein the light chains comprise, from N-terminus to C-terminus, a light chain variable region (VL) and light chain constant (CL) region; and the heavy chains comprise, from N-terminus to C-terminus, (1) a heavy chain region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, (2) a diabody region comprising heavy chain variable region (VH) and light chain variable region (VL), in either order, and (3) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and; wherein the light chains and the heavy chain regions are associated to form Fab regions comprising first and second paratopes, the diabody regions are associated to form a diabody comprising third and fourth paratopes, and the CH2 and CH3 regions are associated to form an Fc domain, and wherein each paratope specifically binds either B7H3 or EphA2, and the paratopes, collectively, specifically bind both B7H3 and EphA2.

11. The antibody of claim 10, wherein the first and second paratopes specifically bind B7H3, and the third and fourth paratopes specifically bind EphA2.

12. The antibody of claim 11, wherein the first and second paratopes specifically bind the same epitope of B7H3, and the third and fourth paratopes specifically bind the same epitope of EphA2.

13. The antibody of claim 11, wherein the first and second paratopes specifically bind different epitopes of B7H3, and / or the third and fourth paratopes specifically bind different epitopes of EphA2.

14. The antibody of claim 10, wherein, the first and third paratopes specifically bind different epitopes B7H3, and the second and fourth paratopes specifically bind EphA2.

15. The antibody of claim 10, wherein, the first and second paratopes specifically bind B7H3 (or EphA2), the third paratope specifically binds one epitope of EphA2 (or B7H3), and the fourth paratope specifically binds a different epitope of EphA2 (or B7H3).Docket No.: AARV-020-PCT 16. The antibody of any of claims 10 to 15, wherein the antibodies comprise one or more CDR sequence sets of an antibody selected from: AB2001, AB2002, AB2003, AB2004 and AB2039.

17. The antibody of any of claims 10 to 16, wherein the antibody comprises one or more of: a heavy chain variable region, a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region, a light chain variable region, a light chain or a diabody region, of an antibody selected from: AB2019, AB2020, AB2025, AB2026, AB2030, AB2031, AB2035, AB2036, AB2037, AB2038, AB2039, and AB2040.

18. The antibody of any of claims 10 to 17, having amino acid sequences at least 90% identical to, at least 95% identical to, at least 98% identical to, at least 99% identical to, or identical to any of AB2019, AB2020, AB2025, AB2026, AB2030, AB2031, AB2035, AB2036, AB2037, AB2038, AB2039, and AB2040.

19. A bi-specific, bivalent antibody that specifically binds B7H3 and EphA2,comprising two paratopes, wherein one paratope specifically binds a first member of the Target Combination Set, and the other paratope specifically binds a second member of the Target Combination Set.

20. The antibody of claim 19, wherein the antibody comprises one or more CDR sequence sets of an antibody selected from: AB2001, AB2002, AB2003, AB2004 and AB2039.

21. The antibody of any of claims 19 to 20, wherein the antibody comprises one or more of: a heavy chain variable region, a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region, a light chain variable region, a light chain or a diabody region, of an antibody selected from: AB2024 and AB2032.

22. The antibody of any of claims 19 to 21, having amino acid sequences at least 90% identical to, at least 95% identical to, at least 98% identical to, at least 99% identical to, or identical to any of AB2024 and AB2032.

23. A multi-specific, trivalent antibody that specifically binds B7H3 and EphA2,comprising three paratopes, wherein each paratope specifically binds a member of a Target Combination Set and the paratopes, collectively, specifically bind all the members of the Target Combination Set.

24. The antibody of claim 23, wherein two paratopes specifically B7H3, e.g., the same or different epitope of B7H3, and one paratope that specifically binds EphA2.Docket No.: AARV-020-PCT 25. The antibody of any of claims 23-24, wherein the antibody comprises one or more CDR sequence sets of an antibody selected from: AB2001, AB2002, AB2003, AB2004 and AB2039.

26. A multi-specific, tetravalent antibody that specifically binds B7H3 and EphA2:comprising four paratopes, wherein (a) each paratope specifically binds either B7H3 and EphA2; and the paratopes, collectively, specifically bind both B7H3 and EphA2.

27. The antibody of claim 26, wherein two paratopes that specifically bind B7H3, e.g., the same or different epitopes B7H3, and two paratopes that specifically bind EphA2, e.g., the same or different epitopes of EphA2.

28. The antibody of claim 27, wherein (a) the paratopes that bind B7H3 occupy the NW and NE positions, and the paratopes that bind EphA2 occupy the SW and SE positions.

29. The antibody of claim 26, wherein three paratopes that specifically bind B7H3, e.g., the same or different epitope of B7H3, and one paratope that specifically binds EphA2.

30. The antibody of claim 26 wherein: (a) two paratopes bind to different epitopes of B7H3 and two paratopes bind to different epitopes of EphA2; (b) one paratope binds to B7H3 and three paratopes bind to different epitopes of EphA2; or (c) three paratopes bind to different epitopes of B7H3 and one paratope binds to an epitope of EphA2.

31. The antibody of claim 26, wherein two paratopes specifically bind B7H3, e.g., the same or different epitope of B7H3, one paratope that specifically binds one epitope of EphA2 and one paratope specifically binds a different epitope of EphA2.

32. The antibody of claim 26, wherein one paratope specifically binds one epitope of B7H3 (or EphA2), one paratope specifically binds a second epitope of B7H3 (or EphA2), one paratope specifically binds a third epitope of B7H3 (EphA2), and one paratope specifically binds a fourth epitope of B7H3 (or EphA2).

33. The antibody of any of claims 26-32, configured in a format selected from:(1) Fab-Diabody-Fc;(2) Diabody-Fc-Fab;(3) Fab-Fc-scFv;(4) Fab / scFv-Fc-Fab / scFv;(5) Diabody-Fc-Diabody;(6) Diabody-Fc-scFv;(7) scFv-Fc-Diabody;Docket No.: AARV-020-PCT (8) scFv-Fc-scFv;(9) Fab-Fc-Diabody;(10) scFv / Fab-Fc-Fab / scFv;(11) Fab-Fc-Fab; and(12) Fab-Fab-Fc.

34. The antibody of any of claims 19-33, wherein the antibody comprises one or more CDR sequence sets of an antibody selected from: AB2001, AB2001, AB2003, AB2004 and AB2039.

35. The antibody of claim 19-34, wherein all of the light chain CDR sequence sets have the same amino acid sequence.

36. The antibody of any of claims 26-35, wherein the antibody comprises:a) a diabody region optionally attached to an Fc region through Spacer 1, and the Fc region attached to a heavy chain region through a Spacer 2;b) a heavy chain region optionally attached through Spacer 3 to a diabody region, and the diabody region optionally attached through a Spacer 4 to an Fc region;c) an Fc region attached to a heavy chain region through a Spacer 5; ord) a heavy chain attached to another heavy chain region through a Spacer 6.

37. The antibody or immunoconjugate of claim 36, wherein Spacers 1-6 independently comprise between 5 and 50 amino acids.

38. The antibody or immunoconjugate of claim 37, wherein Spacers 1-6 are independently selected from a monomer or polymer of a sequence comprising or consisting of (GGGGS)n (SEQ. ID NO:7), (GGGGA)n (SEQ. ID NO:8), or (GGGGG)n (SEQ. ID NO:9), wherein n is any of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

39. The antibody of any of claims 26-35, wherein the antibody comprises a diabody-Fc-Fab format, and spacer between a diabody region and an Fc region, comprises between 5 and 15 amino acids, and spacer between the Fc region and the Fab region comprises between 10 and 20 amino acids.

40. The antibody of any of claims 26-35, wherein the antibody comprises an Fab-diabody-Fc format, and spacer between an Fab region and diabody region comprises between 10 and 20 amino acids, and spacer between the diabody region and the Fc region comprises between 5 and 15 amino acids.

41. The antibody or immunoconjugate of claim 37, wherein Spacers 1-6 are independently selected from GGGGSGGGGSEPKSSDKTHT (SEQ. ID NO:10), LEDKTHTKVEPKSSDocket No.: AARV-020-PCT (SEQ. ID N0:13), SGSETPGTSESATPESGGG (SEQ. ID N0:14), GTTAASGSSGGSSSGA (SEQ. ID N0:15), GGGGSGGGGSGGGTG (SEQ. ID N0:11) or GGGGSGGGGSGGGGSGGGGS (SEQ. ID N0:12).

42. The antibody or immunoconjugate of 36, comprising a diabody region optionally attached to an Fc region through Spacer 1, and the Fc region attached to the heavy chain region through Spacer 2; wherein Spacer 1 and Spacer 2, if present, are selected from the following pairs:Spacer 1 - Diabody-Fc Spacer 2 - Fc-Fab0-5 amino acids 0-4 amino acidsAbout 10 amino acids About 20 amino acidsAbout 10 amino acids About 10 amino acidsAbout 10 amino acids About 5 amino acidsAbout 10 amino acids 0-4 amino acidsAbout 5 amino acids About 20 amino acidsAbout 5 amino acids 0-4 amino acids0-5 amino acids About 20 amino acids0-5 amino acids 0-4 amino acidsAbout 10 amino acids About 20 amino acids43. The antibody or immunoconjugate of claim 42, wherein Spacer 1 and Spacer 2, if present, are selected from the following pairs:Spacer 1 - Diabody-Fc Spacer 2 - Fc-Fab(G4S)0 (no spacer) (G4S)0 (no spacer)(G4S)2 (G4S)4(G4S)2 (G4S)2(G4S)2 (G4S)1(G4S)2 (G4S)0(G4S)1 (G4S)4(G4S)1 (G4S)0(G4S)0 (G4S)4(G4S)0 (G4S)0(G4S)2 (G4S)4wherein G4S may be either G5 or G4A, optionally wherein the linker comprises, at the C-terminus, TG.Docket No.: AARV-020-PCT 44. The antibody or immunoconjugate of claim 36, comprising (i) a heavy chain region optionally attached through Spacer 3 to a diabody region, and the diabody region optionally attached through Spacer 4 to an Fc region, wherein Spacer 3 and Spacer 4, if present, are selected from the following pairs:Spacer 3 - Fab-Diabody Spacer 4 - Diabody-Fc0-5 amino acids 0-4 amino acidsAbout 20 amino acids About 10 amino acidsAbout 5 amino acids About 10 amino acidsAbout 20 amino acids 0-4 amino acidsAbout 15 amino acids About 10 amino acidsAbout 10 amino acids About 10 amino acidsAbout 5 amino acids About 10 amino acids0-5 amino acids About 10 amino acids0-5 amino acids About 5 amino acids45. The antibody or immunoconjugate of claim 44, wherein Spacer 3 and Spacer 4, if present, are selected from the following pairs:Spacer 3 - Fab-Diabody Spacer 4 - Diabody-Fc(G4S)0 (no spacer) (G4S)0 (no spacer)(G4S)4 (G4S)2(G4S)4 (G4S)1(G4S)4 (G4S)0(G4S)3 (G4S)2(G4S)2 (G4S)2(G4S)1 (G4S)2(G4S)0 (G4S)2(G4S)0 (G4S)1wherein G4S may be either G5 or G4A optionally wherein the linker comprises, at the C-terminus, TG.

46. An antibody selected from AB2006, AB2007, AB2008, AB2009, AB2010, AB2011, AB2012, AB2013, AB2015, AB2016, AB2017, AB2018, AB2019, AB2020, AB2021, AB2022, AB2023, AB2024, AB2025, AB2026, AB2027, AB2028, AB2029, AB2030, AB2031, AB2032, AB2033, AB2034, AB2035, AB2036, AB2037, AB2038, AB2039, AB2040, AB2041, or an antibody having amino acid sequences with sequence identify of at least 90%, at least 95%, at least 98%, at least 99% or at least 99.5% therewith.Docket No.: AARV-020-PCT 47. The antibody of claim 46, or having no more than any of 1, 2, 3, 4, 5, 6, 7 or 8 amino acid substitutions with respect thereto.

48. The antibody of any of claims 46-47, wherein any substitutions, additions or deletions are not in the CDR sequences.

49. The antibody of any of claims 46-47, wherein any substitutions, additions or deletions are not in one or both of a light chain variable region or a heavy chain variable region.

50. The antibody of any of claims 1-46, which is an immunoconjugate further comprising one or more payloads conjugated thereto.

51. The antibody of claim 50, wherein at least one payload is selected from the group consisting of: a drug, a radionucleotide, a fluorophore, biotin, RNA, an antibiotic, a protein and a detectable moiety.

52. The antibody of claim 50, wherein at least one of the payloads is selected from AV-DL055B, AV-DL112B, and AV-DL137, maytansinoid, DM-1, DM-4, auristatin, monomethyl auristatin E, monomethyl auristatin F, dolastatin, tubulysin, eribulin, cryptophycin, benzodiazepine, indolino-benzodiazepine, isoquinolidino-benzodiazepine, pyrrolo-benzodiazepine, alpha-amanitin, trichothene, camptothecin derivatives (SN-38, exatecan, belotecan, DXd, topotecan, samrotecan), duocarmycin, DGN549, CC1065, calicheamicin, N-acetyl calicheamicin, an enediyne antibiotic, taxane, doxorubicin derivatives, anthracycline and stereoisomers, azanofide, isosteres, and analogs, hetero dimer or homo dimers or derivatives thereof.

53. The antibody of claim 50, wherein at least one payload is attached to the antibody via a cleavable (enzymatic or non-enzymatic) or non-cleavable or traceless linker.

54. The antibody of claim 53, wherein at least one of the linkers is conjugated through:a) a reduced disulfide bond in the antibody; orb) an amino acid residue (e.g., cysteine or lysine) naturally present or introduced into an amino acid sequence of the antibody.

55. The antibody of claim 54, comprising amino acid substitutions:(a) HC-A118C and LC-V205C; and / or(b) HC-S156C, HC-S239C, and HC-V266C (EU numbering).Docket No.: AARV-020-PCT 56. The antibody of claim 54, wherein at least one of the linkers is conjugated through a non-natural amino acid, disulfide re-bridging, a peptide tag, glycan modification, or an enzymatic modification method used to generate site-specific immunoconjugates.

57. A method of making an immunoconjugate comprising:a) providing an antibody of any of claims 1-56; andb) conjugating one or more payloads to the antibody.

58. The method of claim 57, wherein at least one of the payloads is conjugated to the antibody through a linker.

59. The method of claim 57, wherein at least one of the payloads is conjugated to the antibody through a broken disulfide bond.

60. The method of claim 57, wherein the antibody is a cysteine-substituted antibody, and at least one payload is coupled to the antibody through a substituted cysteine.

61. The method of claim 57, wherein the immunoconjugate has a drug-antibody ratio (“DAR”) of at least any of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12.

62. A collection of one or more nucleic acid molecules that collectively encode paratopes that bind B7H3 and EphA2.

63. The collection of nucleic acid molecules of claim 62, encoding one or more antibodies of any of claims 1-46.

64. The collection of nucleic acid molecules of claim 62, encoding one or more light chains of the antibody of any of claims 1 -46.

65. The collection of nucleic acid molecules of claim 62, encoding one or more heavy chains of the antibody of any of claims 1-46.

66. The collection of nucleic acid molecules of any of claims 62-65, encoding one or more light chains comprising variable regions of paratopes that bind at least one member of the Target Combination Set.

67. The collection of nucleic acid molecules of any of claims 62-65, the nucleic acid molecules further comprising one or more expression control sequences operatively linked to one or more nucleotide sequences encoding the one or more light chain variable regions and / or one or more heavy chain variable regions.Docket No.: AARV-020-PCT 68. The collection of nucleic acid molecules of any of claims 62-67, comprised within one or more vectors, e.g., selected from a plasmid, a viral vector (e.g., a retrovirus, a lentivirus, and adenovirus, and adeno-associated virus, or a herpes simplex virus), a bacterial artificial chromosome, and a yeast artificial chromosome.

69. A cell comprising a collection of nucleic acid molecules of any of claims 62-68.

70. The cell of claim 69, selected from a mammalian cell (e.g., a Chinese hamster ovary (CHO) cell, an NSO cell, an SP2 / 0 cell, a human embryonic kidney HEK 293 cell, or a Per. C6 cell); an insect cell (e.g., an Sf9 cell or a high five (BTI-Tn-5B1-4) cell); a yeast cell (e.g., Pichia pastoris or Saccharomyces cerevisiae), a bacterial cell (e.g., E. coli) and a plant cell.

71. A method of making an antibody comprising:a) providing a cell or cells of any of claims 69-70;b) expressing immunoglobulin molecules encoded by the nucleotide sequences in the cell or cells; andc) recovering the expressed immunoglobulin molecules.

72. The method of claim 71, wherein the antibody is an asymmetric antibody and the cell comprises one or more nucleic acid molecules encoding a heavy chain comprising a knob, a heavy chain comprising a hole, and at least one light chain.

73. The method of claim 72, wherein the cell comprises nucleotide sequences encoding only one light chain, wherein the light chain is configured to associate with different heavy chain regions to produce two paratopes.

74. The method of claim 72, wherein the cell comprises nucleic acids encoding two different light chains, wherein a first light chain is configured to associate with a first heavy chain region to produce a first paratope that binds to a first epitope, and a second light chain is configured to associate with a second heavy chain region to produce a second paratope that binds to a second, different epitope.

75. The method of claim 71, further comprising producing different immunoglobulin chains in different cells, recovering the immunoglobulin chains, and contacting the immunoglobulin chains, wherein the immunoglobulin chains assemble into an antibody.

76. The method of claim 71, further comprising purifying the recovered antibody, e.g. using protein A or protein G.

77. A pharmaceutical composition comprising an antibody or immunoconjugate of any one of claims 1-56, and a pharmaceutically acceptable carrier, diluent, or excipient.Docket No.: AARV-020-PCT 78. The pharmaceutical composition of claim 77, formulated for intravenous injection.

79. A method for treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of any of claims 77-78.

80. The method of claim 79, wherein the cancer is selected from: ACC -Adrenocortical Carcinoma; BLCA - Bladder Urothelial Carcinoma; BRCA-Breast Cancer; CESC - Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma; CHOL-cholangiocarcinoma; COAD - Colon Adenocarcinoma; ESCA - Esophageal Carcinoma; GBM -Glioblastoma Multiforme; HNSC - Head and Neck Squamous Cell Carcinoma; KICH- Kidney Chromophobe; KIRC - Kidney Renal Clear Cell Carcinoma; KIRP - Kidney Renal Papillary Cell Carcinoma; LGG- Brain Lower Grade Glioma; LUAD - Lung Adenocarcinoma; LUSC - Lung Squamous Cell Carcinoma; MESO - Mesothelioma; OV - Ovarian Cancer; PAAD - Pancreatic Adenocarcinoma; PRAD - Prostate Adenocarcinoma; READ - Rectum Adenocarcinoma; SARC - Sarcoma; SKCM - Skin Cutaneous Melanoma; STAD - Stomach Adenocarcinoma; Stomach Adenocarcinoma; STES - Stomach and Esophageal carcinoma; TGCT, Testicular Germ Cell Tumors; THCA - Thyroid Carcinoma; THYM - Thymoma; UCEC - Uterine Corpus Endometrial Carcinoma; UCS - Uterine Carcinosarcoma; UVM - Uveal Melanoma.

81. A method for detecting a cell that expresses B7H3 and / or EphA2, comprising: a) contacting the cell with an antibody or immunoconjugate of any of claims 1-56, to allow binding between the immunoconjugate and the cell; and b) detecting the binding of the antibody to the cell.,82. The method of claim 81, comprising contacting the cell with an immunoconjugate comprising an antibody conjugated to a detectable moiety; and b) detecting the detectable moiety bound to the cell.

83. A method of killing a cell comprising contacting a cell with an antibody or immunoconjugate of any of claims 1-56, wherein one or more paratopes of the antibody specifically bind to an epitope of the cell.

84. The method of claim 83, wherein two different paratopes of the antibody bind to two different epitopes of the cell.

85. The method of claim 83 or 84, wherein the epitope is comprised in a cell surface antigen.

86. Use of an antibody or immunoconjugate of any of claims 1-56 in the manufacture of a medicament.Docket No.: AARV-020-PCT 87. Use of an antibody or immunoconjugate of any of claims 1-56 to produce an immunoconjugate.

88. A multi-specific, tetravalent antibody in a diabody-Fc-Fab format that specifically binds B7H3, comprising two heavy chains and two light chains, wherein the light chains comprise, from N-terminus to C-terminus, a light chain variable region (VL) and light chain constant (CL) region; and the heavy chains comprise, from N-terminus to C-terminus, (1) a diabody region comprising heavy chain variable region (VH) and light chain variable region (VL), in either order, (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region; wherein the diabody regions are associated to form a diabody comprising first and second paratopes, the CH2 and CH3 regions are associated to form an Fc domain, and the light chains and the heavy chain regions are associated to form Fab regions comprising third and fourth paratopes, and wherein each paratope specifically binds an epitope of B7H3, and the paratopes, collectively, specifically bind at least two different epitopes of B7H3.

89. The antibody of claim 88, wherein the first and second paratopes specifically bind B7H3-E1, and the third and fourth paratopes specifically bind B7H3-E2.

90. The antibody of any of claims 88-89, wherein the antibodies comprise one or more CDR sequence sets of an antibody selected from: AB2003, AB2004 and AB2039.

91. The antibody of any of claims 88 to 90, wherein the antibody comprises one or more of: a heavy chain variable region, a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region, a light chain variable region, a light chain or a diabody region, of an antibody selected from: AB2023.

92. The antibody of any of claims 88 to 91, having amino acid sequences at least 90% identical to, at least 95% identical to, at least 98% identical to, at least 99% identical to, or identical to AB2023.

93. A multi-specific, tetravalent antibody in an Fab-diabody-Fc format that specifically binds B7H3 and EphA2 comprising two heavy chains and two light chains, wherein the light chains comprise, from N-terminus to C-terminus, a light chain variable region (VL) and light chain constant (CL) region; and the heavy chains comprise, from N-terminus to C-terminus, (1) a heavy chain region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, (2) a diabody region comprising heavy chain variable region (VH) and light chain variable region (VL), in either order, and (3) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and; wherein the light chains and theDocket No.: AARV-020-PCT heavy chain regions are associated to form Fab regions comprising first and second paratopes, the diabody regions are associated to form a diabody comprising third and fourth paratopes, and the CH2 and CH3 regions are associated to form an Fc domain, and wherein each paratope specifically binds an epitope of B7H3, and the paratopes, collectively, specifically bind at least two different epitopes of B7H3.

94. The antibody of claim 93, wherein the first and second paratopes specifically bind B7H3-E1, and the third and fourth paratopes specifically bind B7H3-E2.

95. The antibody of any of claims 93-94, wherein the antibodies comprise one or more CDR sequence sets of an antibody selected from: AB2003, AB2004 and AB2039.

96. The antibody of any of claims 93 to 95, wherein the antibody comprises one or more of: a heavy chain variable region, a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region, a light chain variable region, a light chain or a diabody region, of an antibody selected from: AB2023.

97. The antibody of any of claims 93 to 96, having amino acid sequences at least 90% identical to, at least 95% identical to, at least 98% identical to, at least 99% identical to, or identical to AB2023.

98. A multi-specific, tetravalent antibody in a diabody-Fc-Fab format that specifically binds EphA2, comprising two heavy chains and two light chains, wherein the light chains comprise, from N-terminus to C-terminus, a light chain variable region (VL) and light chain constant (CL) region; and the heavy chains comprise, from N-terminus to C-terminus, (1) a diabody region comprising heavy chain variable region (VH) and light chain variable region (VL), in either order, (2) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and (3) a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region; wherein the diabody regions are associated to form a diabody comprising first and second paratopes, the CH2 and CH3 regions are associated to form an Fc domain, and the light chains and the heavy chain regions are associated to form Fab regions comprising third and fourth paratopes, and wherein each paratope specifically binds an epitope of EphA2, and the paratopes, collectively, specifically bind at least two different epitopes of EphA2.

99. The antibody of claim 98, wherein the first and second paratopes specifically bind EphA2-E1, and the third and fourth paratopes specifically bind EphA2-E2.

100. The antibody of any of claims 98 to 99, wherein the antibodies comprise one or more CDR sequence sets of an antibody selected from: AB2001 and AB2002.Docket No.: AARV-020-PCT 101. The antibody of any of claims 98 to 100, wherein the antibody comprises one or more of: a heavy chain variable region, a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region, a light chain variable region, a light chain or a diabody region, of an antibody selected from: AB2011 or AB2016.

102. The antibody of any of claims 98 to 101, having amino acid sequences at least 90% identical to, at least 95% identical to, at least 98% identical to, at least 99% identical to, or identical to AB2011 or AB2016.

103. A multi-specific, tetravalent antibody in an Fab-diabody-Fc format that specifically binds EphA2 comprising two heavy chains and two light chains, wherein the light chains comprise, from N-terminus to C-terminus, a light chain variable region (VL) and light chain constant (CL) region; and the heavy chains comprise, from N-terminus to C-terminus, (1) a heavy chain region comprising a heavy chain variable (VH) region and a heavy chain constant 1 (CH1) region, (2) a diabody region comprising heavy chain variable region (VH) and light chain variable region (VL), in either order, and (3) an Fc region comprising heavy chain constant 2 (CH2) region and a heavy chain constant 3 (CH3) region, and; wherein the light chains and the heavy chain regions are associated to form Fab regions comprising first and second paratopes, the diabody regions are associated to form a diabody comprising third and fourth paratopes, and the CH2 and CH3 regions are associated to form an Fc domain, and wherein each paratope specifically binds an epitope of EphA2, and the paratopes, collectively, specifically bind at least two different epitopes of EphA2.

104. The antibody of claim 103, wherein the first and second paratopes specifically bind EphA2-E1, and the third and fourth paratopes specifically bind EphA2-E2.

105. The antibody of any of claims 103 to 104, wherein the antibodies comprise one or more CDR sequence sets of an antibody selected from: AB2001 and AB2002.

106. The antibody of any of claims 103 to 105, wherein the antibody comprises one or more of: a heavy chain variable region, a heavy chain region comprising a heavy chain variable region (VH) and a heavy chain constant 1 (CH1) region, a light chain variable region, a light chain or a diabody region, of an antibody selected from: AB2011 or AB2016.

107. The antibody of any of claims 103 to 106, having amino acid sequences at least 90% identical to, at least 95% identical to, at least 98% identical to, at least 99% identical to, or identical to AB2011 or AB2016.

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