Antibodies and antibody-drug conjugates and methods of use and synthetic processes and intermediates

Abstract

The invention provides antibodies, antibody-drug conjugates comprising an antibody conjugated (directly or through a linker) to a drug moiety of formula: and methods of using the antibody-drug conjugates to treat disease. The invention also provides methods to prepare the drug moieties, antibodies, and antibody-drug conjugates (e.g., ADCs of formula I). The invention also provides antibody-linker-drug intermediates and other intermediates and compounds disclosed herein as well as methods to prepare these antibody-linker-drug intermediates, other intermediates and compounds.

Description

[0001] ANTIBODIES AND ANTIBODY-DRUG CONJUGATES AND METHODS OF USE AND SYNTHETIC PROCESSES AND INTERMEDIATES CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to United States Provisional Application Number 63 / 459,961 that was filed on April 17, 2023 and United States Provisional Application Number 63 / 459,956 that was filed on April 17, 2023. The entire content of the applications referenced above is hereby incorporated by reference herein. FIELD OF THE INVENTION The invention relates to cytotoxic compounds, antibodies that bind to Trop2, and antibody-drug conjugates (ADCs) comprising the cytotoxic compounds conjugated to antibodies including antibodies that bind to Trop2. The invention also relates to methods of using the antibody-drug conjugate compounds for the treatment of diseases including hyperproliferative disorders, such as cancer, methods to prepare the antibodies and antibody- drug conjugates, antibody-linker-drug intermediates, and methods to prepare the antibody- linker-drug intermediates. BACKGROUND OF THE INVENTION Conjugation of drugs to antibodies, either directly or via linkers, involves a consideration of a variety of factors, including the identity and location of the chemical group for conjugation of the drug, the mechanism of drug release, the structural elements providing drug release, and the structural modification to the released free drug. In addition, if the drug is to be released after antibody internalization, the mechanism of drug release must be consonant with the intracellular trafficking of the conjugate. Antibody-drug conjugates (ADCs) have demonstrated considerable utility as anti- cancer agents. In an ADC, a therapeutic agent (also referred to as the cytotoxic drug, payload, or toxin) is covalently linked to an antibody whose antigen is expressed by a cancer or other proliferative cell (tumor associated antigen); for example, an antigen expressed in the tumor, either directly on cancer cells, or on cells in the tumor microenvironment (tumor associated antigen). The antibody, by binding to the antigen, delivers the ADC to the cancer site. There, cleavage of the covalent link or degradation of the antibody leads to the release of the therapeutic agent. On the other hand, while the ADC is circulating in the blood system, the therapeutic agent is inactive because of its linkage to the antibody. Thus, the therapeutic agent used in an ADC can be much more potent than ordinary chemotherapeutic agents because of its highly localized release. While a number of different drug classes have been tried for delivery via antibodies, only a few drug classes have proved efficacious as antibody-drug conjugates, while having a suitable toxicity profile. One drug class includes analogs of FR901464, such as spliceostatin C and thailanstatin A, which are extremely potent inhibitors of eukaryotic RNA splicing. These compounds bind tightly to the SF3b subunit of the U2 snRNA subcomplex, an essential component of the spliceosome (Puthenveetil, S., et al., Bioconjugate Chem., 2016, 27:1880-1888). International Patent Application Publication Number WO 20019 / 060398 discloses certain thailanstatin-based compounds that are reported to be useful as payloads in ADCs and payload-linker compounds useful in connection with ADCs. These ADCs are reported to be useful for treating diseases such as cancer. International Patent Application Publication Number WO 2019 / 060398 also discloses synthetic methods as well as intermediates to prepare the compounds disclosed therein. One specific compound is a compound of the following formula III: III There is an ongoing need for novel antibody-drug conjugates to treat diseases such as cancer. There is also a need for novel drug moieties and antibodies that are useful to prepare antibody-drug conjugates. There is currently a need for synthetic methods and intermediates that can be used to prepare the compounds of formula 8* and formula I (or a diastereomer thereof), and salts thereof as well as other compounds and salts thereof described herein. There is also a need for improved methods for preparing intermediate compounds that can be used to prepare the compounds of formula 8* and formula I and salts thereof. The improved methods and intermediates may reduce the number of synthetic steps, cost, time, impurities, purification steps and / or the amount of waste associated with the existing methods for preparing one or more of the compounds described above. SUMMARY One embodiment provides an antibody-drug conjugate compound comprising an antibody covalently attached to a drug moiety directly (i.e., without a linker) or through alinker of Formula I: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein the drug moiety is: L is a linker; n is 0 or 1; p is an integer from 1 to 20 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20); and Ab is an antibody. One embodiment provides an antibody-drug conjugate compound comprising an antibody covalently attached to a drug moiety directly (i.e., without a linker) or through alinker of Formula I: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein the drug moiety is: L is a linker; n is 0 or 1; p is 1 or more (e.g., 1 to 10 e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10); and Ab is an antibody that binds to Trop2. One embodiment provides an antibody or fragment thereof comprising an immunoglobulin heavy chain variable region polypeptide and an immunoglobulin light chain variable region polypeptide, wherein: the immunoglobulin heavy chain variable region polypeptide comprises a complementarity determining region 1 (HCDR1) comprising an amino acid sequence that is at least 90% identical to NYGMN (SEQ ID NO: 14), a complementarity determining region 2 (HCDR2) comprising an amino acid sequence that is at least 90% identical to WINTKTGEPTYAQEFTG (SEQ ID NO: 21), and a complementarity determining region 3 (HCDR3) comprising an amino acid sequence that is at least 90% identical to GGYGSSYWYFDV (SEQ ID NO: 18); and / or the immunoglobulin light chain variable region polypeptide comprises a complementarity determining region 1 (LCDR1) comprising an amino acid sequence that is at least 90% identical to KASQDVSIAVA (SEQ ID NO: 27), a complementarity determining region 2 (LCDR2) comprising an amino acid sequence that is at least 90% identical to SASYRYT (SEQ ID NO: 29), and a complementarity determining region 3 (LCDR3) comprising an amino acid sequence that is at least 90% identical to QQHYITPLT (SEQ ID NO: 31). One embodiment provides a compound of formula II or a salt thereof, wherein W is a leaving group or -L-X; L is a linker; and X is a reactive group. One embodiment provides a compound of formula , , or a salt thereof (e.g., a pharmaceutically acceptable salt thereof). One embodiment provides a pharmaceutical composition comprising an antibody- drug conjugate compound of Formula I, and a pharmaceutically acceptable diluent, carrier or excipient. One embodiment provides method for treating cancer in a patient (e.g., a mammalian patient such as a human patient) in need thereof, comprising administering a therapeutically effective amount of the antibody drug conjugate compound of formula I as described herein or a pharmaceutically acceptable salt thereof, to the patient. One embodiment provides method for treating cancer in a patient (e.g., a mammalian patient such as a human patient), comprising administering a therapeutically effective amount of the antibody drug conjugate compound of formula I as described herein or a pharmaceutically acceptable salt thereof, to the patient. One embodiment provides method for treating cancer in a mammal (e.g., a human) in need thereof, comprising administering a therapeutically effective amount of the antibody drug conjugate compound of formula I as described herein or a pharmaceutically acceptable salt thereof, to the mammal. One embodiment provides method for treating cancer in a mammal (e.g., a human), comprising administering a therapeutically effective amount of the antibody drug conjugate compound of formula I as described herein or a pharmaceutically acceptable salt thereof, to the mammal. One embodiment provides an antibody-drug conjugate compound of Formula I or a pharmaceutically acceptable salt as described herein for medical therapy. One embodiment provides an antibody drug conjugate compound of formula I as described herein or a pharmaceutically acceptable salt thereof, for use in the therapeutic treatment of cancer. One embodiment provides the use of an antibody-drug conjugate compound of Formula I or a pharmaceutically acceptable salt as described herein for the manufacture of a medicament for the treatment of cancer in a mammal (e.g., a human). One embodiment provides an intermediate for making an antibody-drug conjugate compound of Formula I as described herein. One embodiment provides a method for making an antibody-drug conjugate compound of Formula I or a compound of Formula II as described herein. One embodiment provides an article of manufacture comprising a pharmaceutical composition comprising an antibody-drug conjugate compound of Formula I, a container, and a package insert or label indicating that the pharmaceutical composition can be used to treat cancer. The present invention also provides new synthetic processes and synthetic intermediates that are useful for preparing the compound of formula 8* and I or salts thereof. The present invention also provides new synthetic processes and synthetic intermediates that are useful for preparing additional compounds as described here. Accordingly, one embodiment provides a compound selected from the group consisting of:

[0002] wherein: P is a nitrogen protecting group; each R1is independently a (C1-C6)alkyl or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl; and R2is a (C1-C6)alkyl; or a salt thereof. One embodiment provides a compound selected from the group consisting of: wherein: P is an amine nitrogen protecting group; each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1-C6)alkyl; and R2is a (C1-C6)alkyl or phenyl, wherein the phenyl is optionally substituted with one or more halo or nitro; or a salt thereof. One embodiment provides a method for preparing a compound of formula 8*: or a salt thereof, comprising converting a corresponding compound of formula 7*: or a salt thereof, to the compound of formula 8* or a salt thereof. One embodiment provides a method for preparing a compound of formula 7*: or a salt thereof, comprising converting a corresponding compound of formula 6a*: 6a* or a salt thereof, to the compound of formula 7 or a salt thereof, wherein R2is a (C1-C6)alkyl. One embodiment provides a method for preparing a compound of formula 6a*: 6a* or a salt thereof, comprising converting a corresponding compound of formula 5a*: 5a* or a salt thereof, to the compound of formula 6a* or a salt thereof, wherein: each R1is independently a (C1-C6)alkyl or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl; and R2is a (C1-C6)alkyl. One embodiment provides a method for preparing a compound of formula 5a*: 5a* or a salt thereof, comprising converting a corresponding compound of formula 4a*: 4a* or a salt thereof, to the compound of formula 5a or a salt thereof, wherein: each R1is independently a (C1-C6)alkyl or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl; and R2is a (C1-C6)alkyl. One embodiment provides a method for preparing a compound of formula 4a*: 4a* or a salt thereof, comprising converting a corresponding compound of formula 3a*: 3a* or a salt thereof, to the compound of formula 4a* or a salt thereof, wherein: P is an amine protecting group; and each R1is independently a (C1-C6)alkyl or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl. One embodiment provides a method for preparing a compound of formula 3a*: 3a* or a salt thereof, comprising converting a corresponding compound of formula 2a*: 2a* or a salt thereof, to the compound of formula 3a* or a salt thereof, wherein: P is an amine protecting group; and each R1is independently a (C1-C6)alkyl or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl. One embodiment provides novel synthetic intermediates described herein as well as methods for preparing such intermediates. BRIEF DESCRIPTION OF THE DRAWINGS Figures 1A-1B. Trop2 ADC linker screen. Fig.1A shows that the lysine conjugates with non-cleavable linker have highest potency. The PH-1 family of linker-toxins (L-Ts) were conjugated to Trop2-specific monoclonal antibody (hRS7) and the resulting ADCs were tested for therapeutic efficacy against pre-implanted Trop2-expressing NCI-N87 gastric carcinoma tumors in mice. Non-cleavable Lysine linked PH-1 Linker-Toxins were associated with maximal Tumor Growth Inhibition (TGI) in vivo. L2 (Lys Non-cleavable) DAR8 showed about 88% TGI. L2 (Lys Non-cleavable) DAR4 showed about 77% TGI. L22 (Lys Non-cleavable) showed about 82% TGI. L92 (Lys cleavable) showed about 68% TGI. L18 (Cys Non-cleavable) showed about 65% TGI. Fig.1B shows the experimental drug antibody ratios (DARs) for the ADCs. Figures 2A-2E. Antibody binding profile and binding affinity for Trop2. Fig.2A shows the binding profile of the Daiichi mAb (TINA) having Kd (M): 2.46 E-08. Fig.2B shows the binding profile of the Immunomedics mAb (hRS7) having Kd (M): 2.50 E-09. Fig.2C shows the binding profile of M2.1 having Kd(M): 1.17 E-08. Fig.2D shows the binding profile of M2.2 having Kd(M): 1.32 E-08. Fig.2E shows the binding profile of M2.8 having Kd (M): 8.97 E-09. Figures 3A-3D. M2.1 and M2.8 mAbs recognize human and cynomolgus monkey Trop2. Antibodies were incubated with Chinese Hamster Ovary (CHO) cells that were transiently transfected with species-specific Trop2 cDNAs to test antibodies’ binding profile to human, cynomolgus monkey, or mouse Trop2 proteins. Fig.3A shows M2.1 mAb binding profile. Fig.3B shows hRS7 (IMMU-132) mAb binding profile. Fig.3C shows REA916 Ab (positive control) binding profile. Fig.3D shows TINA (DS-1062) mAb binding profile. Figure 4 shows the assessment for ability of fluorescently labeled Peak Trop2 antibody in binding gastric cancer cells that were pre-bound with Daiichi, or Immunomedics Trop2 antibodies. Moderate binding by Peak Bio mAb even after Trop2 was saturated with Daiichi mAb (TINA) suggests slightly different epitope or partial overlap of epitopes. No binding or steep drop-off by Peak Bio mAb (M2.8) after Trop2 was pre-bound with Immunomedics Trop2 antibody (hRS7) suggests potentially competitive binding for the same epitope. M2.8 mAb epitope is likely to be same as that of hRS7, although further confirmatory study is needed. Figure 5 shows a representative gel electrophoresis characterization of Trop2 antibody and ADCs. M2.1 antibody (Lane 1) was conjugated at a DAR of 2 (Lane 2) or 4 (Lane 3) with Compound of formula 8*. Non-cleavable M2.1-formula 8* conjugates were compared with Cleavable ADCs using alternative linkers. Thailanstatin cysteine (Lane 4) or a lysine conjugate (Lane 5) were in turn compared with pharmaceutical grade Trodelvy (Lane 6) and Enhertu (Lane 7) that release the payload by a similar mechanism. The Lysine conjugated ADCs were more stable under non-reduced conditions. Figures 6A-6F show mass spectra demonstrating efficient conjugation of linker toxin (compound 8* termed PH1) to Trop2 mAb and characterization of DAR2 and DAR4 ADCs. Figs.6A-6C show Trop2 PH1 ADC (DAR2) with an actual DAR of 1.73 and conjugation efficiency of 67%. In particular, Fig.6A shows hydrophobic interaction chromatography (HIC) graph of Trop2 PH1 ADC (DAR2). Fig.6B shows size-exclusion chromatography (SEC) graph of Trop2 PH1 ADC (DAR2). Fig.6C shows DAR population distribution as determined by mass spectrometry for Trop2 PH1 ADC (DAR2). Figs.6D-6F show Trop2 PH1 ADC (DAR4) with an actual DAR of 3.62 and conjugation efficiency of 67%. In particular, Fig.6D shows hydrophobic interaction chromatography (HIC) graph of Trop2 PH1 ADC (DAR4). Fig.6E shows size-exclusion chromatography (SEC) graph of Trop2 PH1 ADC (DAR4). Fig.6F shows DAR population distribution as determined by mass spectrometry for Trop2 PH1 ADC (DAR4). Figure 7 shows internalization of Trop2 mABs following engagement with target receptors in NCI-N87 cells. Internalization assay was performed with Trop2 mAbs: hRS7, M2.1, M2.3, T6-16, TINA. Control Ab used was HuLys 11 targeting chicken lysozyme. T6-16 and TINA appear to internalize more rapidly, but T6-16 shows the highest internalization percentage. Figure 8 shows internalization of TROP2 ADCs that specifically bind and target human Trop2. As cell-surface Trop2 in human cancer cell lines can be proteolytically cleaved and certain antibody-binding epitopes may be lost, internalization of anti-hTrop2 ADCs were tested on a mouse cell line, CT26, stably overexpressing full-length human Trop2. Percent internalization was calculated using formula: [V(tx) / M(tx)] - [V(t0) / M(t0)] * 100 where V is the GMFI of quenched samples (at given time point), and M is the max GMFI / signal when there is 0 quenching (at given time point). Internalization and accumulation of M2.1 and M2.8 ADCs were comparable in CT26 cells overexpressing hTrop2. Figure 9 shows the payload superiority of PH1 (when conjugated on IMMU-132 antibody hRS7) over SN-38 on IMMU-132 antibody (spider plots, n=10 per arm). PH1 was conjugated on an anti-RSV antibody as a control ADC. Figure 10 shows the superiority of Trop-2 PH1 ADC over IMMU-132 (spider plots, n=10 per arm). PH1 was conjugated on an anti-RSV antibody as a control ADC. Figure 11 shows that all tested Trop2 PH1 ADCs regress individual tumors at 3 mg / kg. PH1 was conjugated on an anti-RSV antibody as a control ADC. Figure 12 shows tested Trop2 ADCs. M2.1 PH1 showed higher TGI than M2.3 PH1. For M2.1 PH1 and M2.3 PH1, DAR4 showed higher TGI than DAR2. Figure 13 shows that Trop2 PH1 ADC (M2.8 PH1) demonstrated nanomolar potency in vitro against various cancer cell lines in multiple indications. Figures 14A-14F show ADCs targeting Trop2 have differentiated on-target and off- target activities. Figs.14A-14C show differentiated ADC Targeting Trop2 on-target activity. In particular, Fig.14A shows cytotoxicity data using NCI-N87 Gastric cell line (Trop2high). Fig.14B shows cytotoxicity data using BxPC3 Pancreatic cell line (Trop2high). Fig.14C shows cytotoxicity data using RT112 / 84 bladder cell line (Trop2heterogenous). Figs.14D-14F shows differentiated ADC Targeting Trop2 off-target activity. In particular, Fig.14D shows cytotoxicity data using 786-0 cell line (Trop2negative). Fig.14E shows cytotoxicity data using BJ normal human fibroblast cells. Fig.14F shows cytotoxicity data using HS27 normal human fibroblast cells. Figure 15 shows Trop2 PH1 ADC at 3mg / kg QWx2 Dosing Regimen was associated with highest TGI. In a Trop2 positive tumor model, mice were administered with ADC at different doses (e.g., 0.5, 1, or 3mg / kg) and regimens (e.g., SD, QW x 2, or QW x 3). Tumor growth inhibition (TGI) were monitored. In this study, DAR4 ADC treatments had higher TGI as compared to DAR2 ADC treatments. There was also dose dependent and / or regimen dependent TGI observed (3mg / kg > 1mg / kg > 0.5mg / kg; and QW x 2 > SD). Figure 16 shows Trop2 PH1 ADC could achieve durable tumor regression at lower drug-antibody ratio (DAR). In a Trop2 positive tumor model (nude mice bearing human NCI- N87 gastric tumors with expression level IHC3+), mice were dosed at dosing regimen of QW for 2 weeks (QWx2). Horizontal dotted line indicates mean tumor volume of 200 mm3size at which treatment was initiated. Tumor shrinkage below this line was considered regression. Tumor sizes were monitored. Long term tumor regression (TR) was observed in 50% of treated mice over a period of about 5 months in the group treated with Trop2 PH1 (DAR4) ADC at 3mg / kg. Stable disease was observed in 50% of treated mice over a period of about 5 months in the group treated with Trop2 PH1 (DAR2) ADC at 3mg / kg. Both treatment groups of Trop2 PH1 outperform the treatment group of IMMU-132* at lower DAR (2 or 4 vs 7.6) and / or at lower dose (3mg / kg vs 10 mg / kg). IMMU-132* represents clinical grade IMMU- 132 or Sacituzumab govitecan. Figure 17 shows the cell viability activity (HCT116 cell line) of compound 2A (also referred to as ThA13D2L2) versus compound 2B (also referred to as ThA13D1L2) and the diasteromeric mixture (also referred to a ThA13L2). Figure 18 shows certain exemplary structures of linker-toxins. Figure 19 shows a linker screening study, antibody binding affinity and antibody internalization assays. Figure 20 shows comparison of TGI efficacies of ADCs, and antibody cross-species binding profile. Figures 21A-21B show differentiated NHP safety profile for Trop2 PH1 ADCs. Figure 22 shows low off-target activity, and in vitro potency in various indications. Figure 23 shows in vivo potency of M2.8 PH1 ADC. Figures 24A-24B show the NMR spectra for compound 3*. Figure 24A shows the proton NMR spectrum of compound 3* and figure 24B shows the carbon NMR spectrum of compound 3*. Figures 25A-25B show the NMR spectra for compound 4*. Figure 25A shows the proton NMR spectrum of compound 4* and figure 25B shows the carbon NMR spectrum of compound 4*. Figures 26A-26B show the NMR spectra for compound 5*. Figure 26A shows the proton NMR spectrum of compound 5* and figure 26B shows the carbon NMR spectrum of compound 5*. Figures 27A-27B show the NMR spectra for compound 6*. Figure 27A shows the proton NMR spectrum of compound 6* and figure 27B shows the carbon NMR spectrum of compound 6*. Figure 28 shows the proton NMR spectrum of compound 7*. Figures 29A-29B show the NMR spectra for compound 8*. Figure 29A shows the proton NMR spectrum of compound 8* and figure 29B shows the carbon NMR spectrum of compound 8*. Figures 30A – 30E shows MDR1-low MES-SA uterine sarcoma cells and isogenic MDR1-high MES-SA / MX2 cells were grown in the presence or absence of different ADC payloads or their active payload species. Figure 30A shows ThA13 d2 methyl ester, which is a membrane-permeable representative for the lysine conjugates. The lysine adduct is impermeable. Figure 30B shows ThA13 d2301 (alcohol) species that is released by the cysteine linkers. Figure 30C shows MMAE (vedotin ADCs). Figure 30D shows SN38 (e.g. Trodelvy). Figure 30E shows DXd (e.g. DS-1062). Chemical structures are provided in inset along with their corresponding graphs. In addition, MES-SA / MX2 cells were also grown in the presence or absence of MDR1-specific inhibitors Elacridar and Tariquidar and MDR1- plus CYP 3A4- inhibitor Valspodar that block the p-Glycoproteins from pumping out the ADC payloads in the cell line expressing high levels of MDR1. DETAILED DESCRIPTION Reference will now be made in detail to certain embodiments of the invention, examples of which are illustrated in the accompanying structures and formulas. While the invention will be described in conjunction with the illustrated embodiments, it will be understood that they are not intended to limit the invention to those embodiments. On the contrary, the invention is intended to cover all alternatives, modifications, and equivalents, which may be included within the scope of the present invention as defined by the claims. One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. The present invention is in no way limited to the methods and materials described. Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs, and are consistent with: Singleton et al (1994) Dictionary of Microbiology and Molecular Biology, 2nd Ed., J. Wiley & Sons, New York, NY; and Janeway, C., Travers, P., Walport, M., Shlomchik (2001) Immunobiology, 5th Ed., Garland Publishing, New York. DEFINITIONS Unless stated otherwise, the following terms and phrases as used herein are intended to have the following meanings: When trade names are used herein, applicants intend to independently include the trade name product formulation, the generic drug, and the active pharmaceutical ingredient(s) of the trade name product. An “acceptor human framework” for the purposes herein is a framework comprising the amino acid sequence of a light chain variable domain (VL) framework or a heavy chain variable domain (VH) framework derived from a human immunoglobulin framework or a human consensus framework, as defined below. An acceptor human framework “derived from” a human immunoglobulin framework or a human consensus framework may comprise the same amino acid sequence thereof, or it may contain amino acid sequence changes. In some embodiments, the number of amino acid changes are 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less. In some embodiments, the VL acceptor human framework is identical in sequence to the VL human immunoglobulin framework sequence or human consensus framework sequence. “Affinity” refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity” refers to intrinsic binding affinity which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (Kd). Affinity can be measured by common methods known in the art, including those described herein. Specific illustrative and exemplary embodiments for measuring binding affinity are described in the following. In certain embodiments, an antibody as described herein has dissociation constant (Kd) of ≤ 1μM, ≤ 100 nM, ≤ 10 nM, ≤ 5 nm, ≤ 4 nM, ≤ 3 nM, ≤ 2 nM, ≤ 1 nM, ≤ 0.1 nM, ≤ 0.01 nM, or ≤ 0.001 nM (e.g., 10-8M or less, e.g., from 10-8M to 10-13M, e.g., from 10-9M to 10-13M). An “affinity matured” antibody refers to an antibody with one or more alterations in one or more hypervariable regions (HVRs), compared to a parent antibody which does not possess such alterations, such alterations resulting in an improvement in the affinity of the antibody for antigen. The term “antibody” is used herein in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments so long as they exhibit the desired antigen-binding activity. An “antibody fragment” refers to a molecule other than an intact antibody that comprises a portion of an intact antibody and that binds the antigen to which the intact antibody binds. Examples of antibody fragments include but are not limited to Fv, Fab, Fab', Fab’-SH, F(ab')2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments. The terms “cancer” and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth / proliferation. A “tumor” comprises one or more cancerous cells. Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia or lymphoid malignancies. More particular examples of such cancers include squamous cell cancer (e.g., epithelial squamous cell cancer), lung cancer including small- cell lung cancer, non-small cell lung cancer (“NSCLC”), adenocarcinoma of the lung and squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastric or stomach cancer including gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, rectal cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney or renal cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, as well as head and neck cancer. The term “early stage breast cancer (EBC)” or “early breast cancer” is used herein to refer to breast cancer that has not spread beyond the breast or the axillary lymph nodes. This includes ductal carcinoma in situ and stage I, stage IIA, stage IIB, and stage IIIA breast cancers. Reference to a tumor or cancer as a “Stage 0,” “Stage I,” “Stage II,” “Stage III,” or “Stage IV”, and various sub-stages within this classification, indicates classification of the tumor or cancer using the Overall Stage Grouping or Roman Numeral Staging methods known in the art. Although the actual stage of the cancer is dependent on the type of cancer, in general, a Stage 0 cancer is an in situ lesion, a Stage I cancer is small localized tumor, a Stage II and III cancer is a local advanced tumor which exhibits involvement of the local lymph nodes, and a Stage IV cancer represents metastatic cancer. The specific stages for each type of tumor are known to the skilled clinician. The term “metastatic breast cancer” means the state of breast cancer where the cancer cells are transmitted from the original site to one or more sites elsewhere in the body, by the blood vessels or lymphatics, to form one or more secondary tumors in one or more organs besides the breast. An “advanced” cancer is one which has spread outside the site or organ of origin, either by local invasion or metastasis. Accordingly, the term “advanced” cancer includes both locally advanced and metastatic disease. A “recurrent” cancer is one which has regrown, either at the initial site or at a distant site, after a response to initial therapy, such as surgery. A “locally recurrent” cancer is cancer that returns after treatment in the same place as a previously treated cancer. An “operable” or “resectable” cancer is cancer which is confined to the primary organ and suitable for surgery (resection). A “non-resectable” or “unresectable” cancer is not able to be removed (resected) by surgery. The term “chimeric” antibody refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species. The “class” of an antibody refers to the type of constant domain or constant region possessed by its heavy chain. There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called α, δ, ε, γ, and µ, respectively. The term “cytotoxic agent” as used herein refers to a substance that inhibits or prevents a cellular function and / or causes cell death or destruction. Cytotoxic agents include, but are not limited to, radioactive isotopes (e.g., At211, I131, I125, Y90, Re186, Re188, Sm153, Bi212, P32, Pb212and radioactive isotopes of Lu); chemotherapeutic agents or drugs (e.g., methotrexate, adriamicin, vinca alkaloids (vincristine, vinblastine, etoposide), doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin or other intercalating agents); growth inhibitory agents; enzymes and fragments thereof such as nucleolytic enzymes; antibiotics; toxins such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin, including fragments and / or variants thereof; and the various antitumor or anticancer agents disclosed below. “Effector functions” refer to those biological activities attributable to the Fc region of an antibody, which vary with the antibody isotype. Examples of antibody effector functions include: C1q binding and complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor); and B cell activation. An “effective amount” of an agent, e.g., a pharmaceutical formulation, refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic or prophylactic result. The effective amount of the drug for treating cancer may reduce the number of cancer cells; reduce the tumor size; inhibit (i.e., slow to some extent and preferably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and preferably stop) tumor metastasis; inhibit, to some extent, tumor growth; and / or relieve to some extent one or more of the symptoms associated with the cancer. To the extent the drug may prevent growth and / or kill existing cancer cells, it may be cytostatic and / or cytotoxic. The effective amount may extend progression free survival (e.g., as measured by Response Evaluation Criteria for Solid Tumors, RECIST, or CA-125 changes), result in an objective response (including a partial response, PR, or complete response, CR), increase overall survival time, and / or improve one or more symptoms of cancer (e.g. as assessed by FOSI). The term “epitope” refers to the particular site on an antigen molecule to which an antibody binds. The term “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. In one embodiment, a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl-terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. “Framework” or “FR” refers to variable domain residues other than hypervariable region (HVR) residues. The FR of a variable domain generally consists of four FR domains: FR1, FR2, FR3, and FR4. Accordingly, the HVR and FR sequences generally appear in the following sequence in VH (or VL): FR1-H1(L1)-FR2-H2(L2)-FR3-H3(L3)-FR4. The terms “full length antibody,” “intact antibody,” and “whole antibody” are used herein interchangeably to refer to an antibody having a structure substantially similar to a native antibody structure or having heavy chains that contain an Fc region as defined herein. The terms “host cell,” “host cell line,” and “host cell culture” are used interchangeably and refer to cells into which exogenous nucleic acid has been introduced, including the progeny of such cells. Host cells include “transformants” and “transformed cells,” which include the primary transformed cell and progeny derived therefrom without regard to the number of passages. Progeny may not be completely identical in nucleic acid content to a parent cell, but may contain mutations. Mutant progeny that have the same function or biological activity as screened or selected for in the originally transformed cell are included herein. A “human antibody” is one which possesses an amino acid sequence which corresponds to that of an antibody produced by a human or a human cell or derived from a non-human source that utilizes human antibody repertoires or other human antibody- encoding sequences. This definition of a human antibody specifically excludes a humanized antibody comprising non-human antigen-binding residues. A “human consensus framework” is a framework which represents the most commonly occurring amino acid residues in a selection of human immunoglobulin VL or VH framework sequences. Generally, the selection of human immunoglobulin VL or VH sequences is from a subgroup of variable domain sequences. Generally, the subgroup of sequences is a subgroup as in Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, NIH Publication 91-3242, Bethesda MD (1991), vols.1-3. In one embodiment, for the VL, the subgroup is subgroup kappa I as in Kabat et al., supra. In one embodiment, for the VH, the subgroup is subgroup III as in Kabat et al., supra. A “humanized” antibody refers to a chimeric antibody comprising amino acid residues from non-human HVRs and amino acid residues from human FRs. In certain embodiments, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the HVRs (e.g., CDRs) correspond to those of a non-human antibody, and all or substantially all of the FRs correspond to those of a human antibody. A humanized antibody optionally may comprise at least a portion of an antibody constant region derived from a human antibody. A “humanized form” of an antibody, e.g., a non-human antibody, refers to an antibody that has undergone humanization. The term “hypervariable region” or “HVR,” as used herein, refers to each of the regions of an antibody variable domain which are hypervariable in sequence and / or form structurally defined loops (“hypervariable loops”). Generally, native four-chain antibodies comprise six HVRs; three in the VH (H1, H2, H3), and three in the VL (L1, L2, L3). HVRs generally comprise amino acid residues from the hypervariable loops and / or from the “complementarity determining regions” (CDRs), the latter being of highest sequence variability and / or involved in antigen recognition. An “immunoconjugate” is an antibody conjugated to one or more heterologous molecule(s), including but not limited to a cytotoxic agent. A “patient” or “individual” or “subject” is a mammal. Mammals include, but are not limited to, domesticated animals (e.g., cows, sheep, cats, dogs, and horses), primates (e.g., humans and non-human primates such as monkeys), rabbits, and rodents (e.g., mice and rats). In certain embodiments, the patient, individual, or subject is a human. In some embodiments, the patient may be a “cancer patient,” i.e. one who is suffering or at risk for suffering from one or more symptoms of cancer, in particular gastric or breast cancer. A “patient population” refers to a group of cancer patients. Such populations can be used to demonstrate statistically significant efficacy and / or safety of a drug. A “relapsed” patient is one who has signs or symptoms of cancer after remission. Optionally, the patient has relapsed after adjuvant or neoadjuvant therapy. A cancer or biological sample which “displays HER expression, amplification, or activation” is one which, in a diagnostic test, expresses (including overexpresses) a HER receptor, has amplified HER gene, and / or otherwise demonstrates activation or phosphorylation of a HER receptor. “Neoadjuvant therapy” or “preoperative therapy” herein refers to therapy given prior to surgery. The goal of neoadjuvant therapy is to provide immediate systemic treatment, potentially eradicating micrometastases that would otherwise proliferate if the standard sequence of surgery followed by systemic therapy were followed. Neoadjuvant therapy may also help to reduce tumor size thereby allowing complete resection of initially unresectable tumors or preserving portions of the organ and its functions. Furthermore, neoadjuvant therapy permits an in vivo assessment of drug efficacy, which may guide the choice of subsequent treatments. “Adjuvant therapy” herein refers to therapy given after definitive surgery, where no evidence of residual disease can be detected, so as to reduce the risk of disease recurrence. The goal of adjuvant therapy is to prevent recurrence of the cancer, and therefore to reduce the chance of cancer-related death. Adjuvant therapy herein specifically excludes neoadjuvant therapy. “Definitive surgery” is used as that term is used within the medical community. Definitive surgery includes, for example, procedures, surgical or otherwise, that result in removal or resection of the tumor, including those that result in the removal or resection of all grossly visible tumor. Definitive surgery includes, for example, complete or curative resection or complete gross resection of the tumor. Definitive surgery includes procedures that occur in one or more stages, and includes, for example, multi-stage surgical procedures where one or more surgical or other procedures are performed prior to resection of the tumor. Definitive surgery includes procedures to remove or resect the tumor including involved organs, parts of organs and tissues, as well as surrounding organs, such as lymph nodes, parts of organs, or tissues. Removal may be incomplete such that tumor cells might remain even though undetected. “Survival” refers to the patient remaining alive, and includes disease free survival (DFS), progression free survival (PFS) and overall survival (OS). Survival can be estimated by the Kaplan-Meier method, and any differences in survival are computed using the stratified log-rank test. “Progression-Free Survival” (PFS) is the time from the first day of treatment to documented disease progression (including isolated CNS progression) or death from any cause on study, whichever occurs first. “Disease free survival (DFS)” refers to the patient remaining alive, without return of the cancer, for a defined period of time such as about 1 year, about 2 years, about 3 years, about 4 years, about 5 years, about 10 years, etc., from initiation of treatment or from initial diagnosis. In one aspect of the invention, DFS is analyzed according to the intent-to-treat principle, i.e., patients are evaluated on the basis of their assigned therapy. The events used in the analysis of DFS can include local, regional and distant recurrence of cancer, occurrence of secondary cancer, and death from any cause in patients without a prior event (e.g, breast cancer recurrence or second primary cancer). “Overall survival” refers to the patient remaining alive for a defined period of time, such as about 1 year, about 2 years, about 3 years, about 4 years, about 5 years, about 10 years, etc., from initiation of treatment or from initial diagnosis. In the studies underlying the invention the event used for survival analysis was death from any cause. By “extending survival” is meant increasing DFS and / or OS in a treated patient relative to an untreated patient, or relative to a control treatment protocol. Survival is monitored for at least about six months, or at least about 1 year, or at least about 2 years, or at least about 3 years, or at least about 4 years, or at least about 5 years, or at least about 10 years, etc., following the initiation of treatment or following the initial diagnosis. By “monotherapy” is meant a therapeutic regimen that includes only a single therapeutic agent for the treatment of the cancer or tumor during the course of the treatment period. By “maintenance therapy” is meant a therapeutic regimen that is given to reduce the likelihood of disease recurrence or progression. Maintenance therapy can be provided for any length of time, including extended time periods up to the life-span of the subject. Maintenance therapy can be provided after initial therapy or in conjunction with initial or additional therapies. Dosages used for maintenance therapy can vary and can include diminished dosages as compared to dosages used for other types of therapy. An “isolated antibody” is one which has been separated from a component of its natural environment. In some embodiments, an antibody is purified to greater than 95% or 99% purity as determined by, for example, electrophoretic (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatographic (e.g., ion exchange or reverse phase HPLC). For review of methods for assessment of antibody purity, see, e.g., Flatman et al., J. Chromatogr. B 848:79-87 (2007). An “isolated nucleic acid” refers to a nucleic acid molecule that has been separated from a component of its natural environment. An isolated nucleic acid includes a nucleic acid molecule contained in cells that ordinarily contain the nucleic acid molecule, but the nucleic acid molecule is present extrachromosomally or at a chromosomal location that is different from its natural chromosomal location. “Isolated nucleic acid encoding an antibody” refers to one or more nucleic acid molecules encoding antibody heavy and light chains (or fragments thereof), including such nucleic acid molecule(s) in a single vector or separate vectors, and such nucleic acid molecule(s) present at one or more locations in a host cell. The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical and / or bind the same epitope, except for possible variant antibodies, e.g., containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present invention may be made by a variety of techniques, including but not limited to the hybridoma method, recombinant DNA methods, phage- display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci, such methods and other exemplary methods for making monoclonal antibodies being described herein. A “naked antibody” refers to an antibody that is not conjugated to a heterologous moiety (e.g., a cytotoxic moiety) or radiolabel. The naked antibody may be present in a pharmaceutical formulation. “Native antibodies” refer to naturally occurring immunoglobulin molecules with varying structures. For example, native IgG antibodies are heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light chains and two identical heavy chains that are disulfide-bonded. From N- to C-terminus, each heavy chain has a variable region (VH), also called a variable heavy domain or a heavy chain variable domain, followed by three constant domains (CH1, CH2, and CH3). Similarly, from N- to C-terminus, each light chain has a variable region (VL), also called a variable light domain or a light chain variable domain, followed by a constant light (CL) domain. The light chain of an antibody may be assigned to one of two types, called kappa (κ) and lambda (λ), based on the amino acid sequence of its constant domain. A “vial” is a container suitable for holding a liquid or lyophilized preparation. In one embodiment, the vial is a single-use vial, e.g. a 20-cc single-use vial with a stopper. The term “package insert” is used to refer to instructions customarily included in commercial packages of therapeutic products, that contain information about the indications, usage, dosage, administration, combination therapy, contraindications and / or warnings concerning the use of such therapeutic products. “Percent (%) amino acid sequence identity” with respect to a reference polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, Clustal X, Clustal W, ALIGN or Megalign (DNASTAR) software. The term “pharmaceutical formulation” refers to a preparation which is in such form as to permit the biological activity of an active ingredient contained therein to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered. A “pharmaceutically acceptable carrier” refers to an ingredient in a pharmaceutical formulation, other than an active ingredient, which is nontoxic to a subject. A pharmaceutically acceptable carrier includes, but is not limited to, a buffer, excipient, stabilizer, or preservative. As used herein, “treatment” (and grammatical variations thereof such as “treat” or “treating”) refers to clinical intervention in an attempt to alter the natural course of the individual being treated, and can be performed either for prophylaxis or during the course of clinical pathology. Desirable effects of treatment include, but are not limited to, preventing occurrence or recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis. In some embodiments, antibodies of the invention are used to delay development of a disease or to slow the progression of a disease. By “co-administering” is meant intravenously administering two (or more) drugs during the same administration, rather than sequential infusions of the two or more drugs. Generally, this will involve combining the two (or more) drugs into the same IV bag prior to co-administration thereof. A drug that is administered “concurrently” with one or more other drugs is administered during the same treatment cycle, on the same day of treatment as the one or more other drugs, and, optionally, at the same time as the one or more other drugs. For instance, for cancer therapies given every 3 weeks, the concurrently administered drugs are each administered on day-1 of a 3-week cycle. A "chemotherapeutic agent" refers to a chemical compound useful in the treatment of cancer. Examples of chemotherapeutic agents include alkylating agents such as thiotepa and cyclosphosphamide (CYTOXAN®); alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide and trimethylomelamine; acetogenins (especially bullatacin and bullatacinone); delta-9-tetrahydrocannabinol (dronabinol, MARINOL®); beta-lapachone; lapachol; colchicines; betulinic acid; a camptothecin (including the synthetic analogue topotecan (HYCAMTIN®), CPT-11 (irinotecan, CAMPTOSAR®), acetylcamptothecin, scopolectin, and 9-aminocamptothecin); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); podophyllotoxin; podophyllinic acid; teniposide; cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine, chlorophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosoureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics (e.g., calicheamicin, especially calicheamicin gamma1I and calicheamicin omegaI1 (see, e.g., Nicolaou et al., Angew. Chem Intl. Ed. Engl., 33: 183-186 (1994)); CDP323, an oral alpha-4 integrin inhibitor; dynemicin, including dynemicin A; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycins, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin (including ADRIAMYCIN®, morpholino-doxorubicin, cyanomorpholino- doxorubicin, 2-pyrrolino-doxorubicin, doxorubicin HCl liposome injection (DOXIL®), liposomal doxorubicin TLC D-99 (MYOCET®), peglylated liposomal doxorubicin (CAELYX®), and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, porfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate, gemcitabine (GEMZAR®), tegafur (UFTORAL®), capecitabine (XELODA®), an epothilone, and 5-fluorouracil (5-FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti- adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfornithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; 2- ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, OR); razoxane; rhizoxin; sizofiran; spirogermanium; tenuazonic acid; triaziquone; 2,2’,2’-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine (ELDISINE®, FILDESIN®); dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); thiotepa; taxoid, e.g., paclitaxel (TAXOL®), albumin-engineered nanoparticle formulation of paclitaxel (ABRAXANETM), and docetaxel (TAXOTERE®); chloranbucil; 6-thioguanine; mercaptopurine; methotrexate; platinum agents such as cisplatin, oxaliplatin (e.g., ELOXATIN®), and carboplatin; vincas, which prevent tubulin polymerization from forming microtubules, including vinblastine (VELBAN®), vincristine (ONCOVIN®), vindesine (ELDISINE®, FILDESIN®), and vinorelbine (NAVELBINE®); etoposide (VP-16); ifosfamide; mitoxantrone; leucovorin; novantrone; edatrexate; daunomycin; aminopterin; ibandronate; topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid, including bexarotene (TARGRETIN®); bisphosphonates such as clodronate (for example, BONEFOS® or OSTAC®), etidronate (DIDROCAL®), NE-58095, zoledronic acid / zoledronate (ZOMETA®), alendronate (FOSAMAX®), pamidronate (AREDIA®), tiludronate (SKELID®), or risedronate (ACTONEL®); troxacitabine (a 1,3- dioxolane nucleoside cytosine analog); antisense oligonucleotides, particularly those that inhibit expression of genes in signaling pathways implicated in aberrant cell proliferation, such as, for example, PKC-alpha, Raf, H-Ras, and epidermal growth factor receptor (EGF- R); vaccines such as THERATOPE® vaccine and gene therapy vaccines, for example, ALLOVECTIN® vaccine, LEUVECTIN® vaccine, and VAXID® vaccine; topoisomerase 1 inhibitor (e.g., LURTOTECAN®); rmRH (e.g., ABARELIX®); BAY439006 (sorafenib; Bayer); SU-11248 (sunitinib, SUTENT®, Pfizer); perifosine, COX-2 inhibitor (e.g., celecoxib or etoricoxib), proteosome inhibitor (e.g., PS341); bortezomib (VELCADE®); CCI-779; tipifarnib (R11577); orafenib, ABT510; Bcl-2 inhibitor such as oblimersen sodium (GENASENSE®); pixantrone; EGFR inhibitors (see definition below); tyrosine kinase inhibitors; serine-threonine kinase inhibitors such as rapamycin (sirolimus, RAPAMUNE®); farnesyltransferase inhibitors such as lonafarnib (SCH 6636, SARASARTM); and pharmaceutically acceptable salts, acids or derivatives of any of the above; as well as combinations of two or more of the above such as CHOP, an abbreviation for a combined therapy of cyclophosphamide, doxorubicin, vincristine, and prednisolone; and FOLFOX, an abbreviation for a treatment regimen with oxaliplatin (ELOXATINTM) combined with 5-FU and leucovorin. Chemotherapeutic agents as defined herein include “anti-hormonal agents” or “endocrine therapeutics” which act to regulate, reduce, block, or inhibit the effects of hormones that can promote the growth of cancer. They may be hormones themselves, including, but not limited to: anti-estrogens with mixed agonist / antagonist profile, including, tamoxifen (NOLVADEX®), 4-hydroxytamoxifen, toremifene (FARESTON®), idoxifene, droloxifene, raloxifene (EVISTA®), trioxifene, keoxifene, and selective estrogen receptor modulators (SERMs) such as SERM3; pure anti-estrogens without agonist properties, such as fulvestrant (FASLODEX®), and EM800 (such agents may block estrogen receptor (ER) dimerization, inhibit DNA binding, increase ER turnover, and / or suppress ER levels); aromatase inhibitors, including steroidal aromatase inhibitors such as formestane and exemestane (AROMASIN®), and nonsteroidal aromatase inhibitors such as anastrazole (ARIMIDEX®), letrozole (FEMARA®) and aminoglutethimide, and other aromatase inhibitors include vorozole (RIVISOR®), megestrol acetate (MEGASE®), fadrozole, and 4(5)-imidazoles; lutenizing hormone-releaseing hormone agonists, including leuprolide (LUPRON® and ELIGARD®), goserelin, buserelin, and tripterelin; sex steroids, including progestines such as megestrol acetate and medroxyprogesterone acetate, estrogens such as diethylstilbestrol and premarin, and androgens / retinoids such as fluoxymesterone, all transretionic acid and fenretinide; onapristone; anti-progesterones; estrogen receptor down- regulators (ERDs); anti-androgens such as flutamide, nilutamide and bicalutamide; and pharmaceutically acceptable salts, acids or derivatives of any of the above; as well as combinations of two or more of the above. A “fixed ” or “flat” dose of a therapeutic agent herein refers to a dose that is administered to a human patient without regard for the weight (WT) or body surface area (BSA) of the patient. The fixed or flat dose is therefore not provided as a mg / kg dose or a mg / m2 dose, but rather as an absolute amount of the therapeutic agent. A “loading” dose herein generally comprises an initial dose of a therapeutic agent administered to a patient, and is followed by one or more maintenance dose(s) thereof. Generally, a single loading dose is administered, but multiple loading doses are contemplated herein. Usually, the amount of loading dose(s) administered exceeds the amount of the maintenance dose(s) administered and / or the loading dose(s) are administered more frequently than the maintenance dose(s), so as to achieve the desired steady-state concentration of the therapeutic agent earlier than can be achieved with the maintenance dose(s). A “maintenance” dose herein refers to one or more doses of a therapeutic agent administered to the patient over a treatment period. Usually, the maintenance doses are administered at spaced treatment intervals, such as approximately every week, approximately every 2 weeks, approximately every 3 weeks, or approximately every 4 weeks, preferably every 3 weeks. “Infusion” or “infusing” refers to the introduction of a drug-containing solution into the body through a vein for therapeutic purposes. Generally, this is achieved via an intravenous (IV) bag. An “intravenous bag” or “IV bag” is a bag that can hold a solution which can be administered via the vein of a patient. In one embodiment, the solution is a saline solution (e.g. about 0.9% or about 0.45% NaCl). Optionally, the IV bag is formed from polyolefin or polyvinal chloride. The term “variable region” or “variable domain” refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to antigen. The variable domains of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three hypervariable regions (HVRs). (See, e.g., Kindt et al. Kuby Immunology, 6thed., W.H. Freeman and Co., page 91 (2007).) A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind a particular antigen may be isolated using a VH or VL domain from an antibody that binds the antigen to screen a library of complementary VL or VH domains, respectively. See, e.g., Portolano et al., J. Immunol.150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991). The term “vector,” as used herein, refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. The term includes the vector as a self- replicating nucleic acid structure as well as the vector incorporated into the genome of a host cell into which it has been introduced. Certain vectors are capable of directing the expression of nucleic acids to which they are operatively linked. Such vectors are referred to herein as “expression vectors.” A “free cysteine amino acid” refers to a cysteine amino acid residue which has been engineered into a parent antibody, has a thiol functional group (-SH), and is not paired as an intramolecular or intermolecular disulfide bridge. “Linker”, “Linker Unit”, or “link” means a chemical moiety comprising a chain of atoms that covalently attaches an antibody to a drug moiety. When indicating the number of substituents, the term “one or more” refers to the range from one substituent to the highest possible number of substitution, i.e. replacement of one hydrogen up to replacement of all hydrogens by substituents. The term “substituent” denotes an atom or a group of atoms replacing a hydrogen atom on the parent molecule. The term “substituted” denotes that a specified group bears one or more substituents. Where any group may carry multiple substituents and a variety of possible substituents is provided, the substituents are independently selected and need not to be the same. The term “unsubstituted” means that the specified group bears no substituents. The term “optionally substituted” means that the specified group is unsubstituted or substituted by one or more substituents, independently chosen from the group of possible substituents. When indicating the number of substituents, the term “one or more” means from one substituent to the highest possible number of substitution, i.e. replacement of one hydrogen up to replacement of all hydrogens by substituents. The term “alkyl” as used herein refers to a saturated linear or branched-chain monovalent hydrocarbon radical of any length from one to twelve carbon atoms (C1−C12), wherein the alkyl radical may be optionally substituted independently with one or more substituents described below. In another embodiment, an alkyl radical is one to eight carbon atoms (C1−C8), or one to six carbon atoms (C1−C6). Examples of alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), 1-propyl (n-Pr, n-propyl, - CH2CH2CH3), 2-propyl (i-Pr, i-propyl, -CH(CH3)2), 1-butyl (n-Bu, n-butyl, - CH2CH2CH2CH3), 2-methyl-1-propyl (i-Bu, i-butyl, -CH2CH(CH3)2), 2-butyl (s-Bu, s-butyl, - CH(CH3)CH2CH3), 2-methyl-2-propyl (t-Bu, t-butyl, -C(CH3)3), 1-pentyl (n-pentyl, - CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2- methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1- butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2CH(CH3)CH2CH3), 1-hexyl (- CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH3), 3-hexyl (- CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl (-CH(CH3)CH(CH3)CH2CH3), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3- pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2- butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3, 1-heptyl, 1-octyl, and the like. The term “alkylene” as used herein refers to a saturated linear or branched-chain divalent hydrocarbon radical of any length from one to twelve carbon atoms (C1−C12), wherein the alkylene radical may be optionally substituted independently with one or more substituents described below. In another embodiment, an alkylene radical is one to eight carbon atoms (C1−C8), or one to six carbon atoms (C1−C6). Examples of alkylene groups include, but are not limited to, methylene (-CH2-), ethylene (−CH2CH2−), propylene (− CH2CH2CH2−), and the like. The term “alkenyl” refers to linear or branched-chain monovalent hydrocarbon radical of any length from two to eight carbon atoms (C2−C8) with at least one site of unsaturation, i.e., a carbon-carbon, sp2double bond, wherein the alkenyl radical may be optionally substituted independently with one or more substituents described herein, and includes radicals having “cis” and “trans” orientations, or alternatively, “E” and “Z” orientations. Examples include, but are not limited to, ethylenyl or vinyl (−CH=CH2), allyl (− CH2CH=CH2), and the like. The term “alkenylene” refers to linear or branched-chain divalent hydrocarbon radical of any length from two to eight carbon atoms (C2−C8) with at least one site of unsaturation, i.e., a carbon-carbon, sp2double bond, wherein the alkenylene radical may be optionally substituted independently with one or more substituents described herein, and includes radicals having “cis” and “trans” orientations, or alternatively, “E” and “Z” orientations. Examples include, but are not limited to, ethylenylene or vinylene (−CH=CH−), allyl (− CH2CH=CH−), and the like. The term “alkynyl” refers to a linear or branched monovalent hydrocarbon radical of any length from two to eight carbon atoms (C2−C8) with at least one site of unsaturation, i.e., a carbon-carbon, sp triple bond, wherein the alkynyl radical may be optionally substituted independently with one or more substituents described herein. Examples include, but are not limited to, ethynyl (-C≡CH), propynyl (propargyl, -CH2C≡CH), and the like. The term “alkynylene” refers to a linear or branched divalent hydrocarbon radical of any length from two to eight carbon atoms (C2−C8) with at least one site of unsaturation, i.e., a carbon-carbon, sp triple bond, wherein the alkynylene radical may be optionally substituted independently with one or more substituents described herein. Examples include, but are not limited to, ethynylene (-C≡C-), propynylene (propargylene, -CH2C≡C-), and the like. The terms “carbocycle”, “carbocyclyl”, “carbocyclic ring” and “cycloalkyl” refer to a monovalent non-aromatic, saturated or partially unsaturated ring having 3 to 12 carbon atoms (C3−C12) as a monocyclic ring or 7 to 12 carbon atoms as a bicyclic ring. Bicyclic carbocycles having 7 to 12 atoms can be arranged, for example, as a bicyclo [4,5], [5,5], [5,6] or [6,6] system, and bicyclic carbocycles having 9 or 10 ring atoms can be arranged as a bicyclo [5,6] or [6,6] system, or as bridged systems such as bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane and bicyclo[3.2.2]nonane. Spiro moieties are also included within the scope of this definition. Examples of monocyclic carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3- enyl, cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, 1-cyclohex-3-enyl, cyclohexadienyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, and the like. Carbocyclyl groups are optionally substituted independently with one or more substituents described herein. “Aryl” means a monovalent aromatic hydrocarbon radical of 6-20 carbon atoms (C6− C20) derived by the removal of one hydrogen atom from a single carbon atom of a parent aromatic ring system. Some aryl groups are represented in the exemplary structures as “Ar”. Aryl includes bicyclic radicals comprising an aromatic ring fused to a saturated, partially unsaturated ring, or aromatic carbocyclic ring. Typical aryl groups include, but are not limited to, radicals derived from benzene (phenyl), substituted benzenes, naphthalene, anthracene, biphenyl, indenyl, indanyl, 1,2-dihydronaphthalene, 1,2,3,4-tetrahydronaphthyl, and the like. Aryl groups are optionally substituted independently with one or more substituents described herein. “Arylene” means a divalent aromatic hydrocarbon radical of 6-20 carbon atoms (C6− C20) derived by the removal of two hydrogen atom from a two carbon atoms of a parent aromatic ring system. Some arylene groups are represented in the exemplary structures as “Ar”. Arylene includes bicyclic radicals comprising an aromatic ring fused to a saturated, partially unsaturated ring, or aromatic carbocyclic ring. Typical arylene groups include, but are not limited to, radicals derived from benzene (phenylene), substituted benzenes, naphthalene, anthracene, biphenylene, indenylene, indanylene, 1,2-dihydronaphthalene, 1,2,3,4-tetrahydronaphthyl, and the like. Arylene groups are optionally substituted with one or more substituents described herein. The terms “heterocycle,” “heterocyclyl” and “heterocyclic ring” are used interchangeably herein and refer to a saturated or a partially unsaturated (i.e., having one or more double and / or triple bonds within the ring) carbocyclic radical of 3 to about 20 ring atoms in which at least one ring atom is a heteroatom selected from nitrogen, oxygen, phosphorus and sulfur, the remaining ring atoms being C, where one or more ring atoms is optionally substituted independently with one or more substituents described below. A heterocycle may be a monocycle having 3 to 7 ring members (2 to 6 carbon atoms and 1 to 4 heteroatoms selected from N, O, P, and S) or a bicycle having 7 to 10 ring members (4 to 9 carbon atoms and 1 to 6 heteroatoms selected from N, O, P, and S), for example: a bicyclo [4,5], [5,5], [5,6], or [6,6] system. Heterocycles are described in Paquette, Leo A.; “Principles of Modern Heterocyclic Chemistry” (W.A. Benjamin, New York, 1968), particularly Chapters 1, 3, 4, 6, 7, and 9; “The Chemistry of Heterocyclic Compounds, A series of Monographs” (John Wiley & Sons, New York, 1950 to present), in particular Volumes 13, 14, 16, 19, and 28; and J. Am. Chem. Soc. (1960) 82:5566. “Heterocyclyl” also includes radicals where heterocycle radicals are fused with a saturated, partially unsaturated ring, or aromatic carbocyclic or heterocyclic ring. Examples of heterocyclic rings include, but are not limited to, morpholin-4-yl, piperidin-1-yl, piperazinyl, piperazin-4-yl-2-one, piperazin-4-yl-3-one, pyrrolidin-1-yl, thiomorpholin-4-yl, S-dioxothiomorpholin-4-yl, azocan-1-yl, azetidin-1-yl, octahydropyrido[1,2-a]pyrazin-2-yl, [1,4]diazepan-1-yl, pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidino, morpholino, thiomorpholino, thioxanyl, piperazinyl, homopiperazinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 2-pyrrolinyl, 3-pyrrolinyl, indolinyl, 2H- pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazolidinylimidazolinyl, imidazolidinyl, 3- azabicyco[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, azabicyclo[2.2.2]hexanyl, 3H-indolyl quinolizinyl and N-pyridyl ureas. Spiro moieties are also included within the scope of this definition. Examples of a heterocyclic group wherein 2 ring atoms are substituted with oxo (=O) moieties are pyrimidinonyl and 1,1-dioxo-thiomorpholinyl. The heterocycle groups herein are optionally substituted independently with one or more substituents described herein. The term “heteroaryl” refers to a monovalent aromatic radical of 5-, 6-, or 7- membered rings, and includes fused ring systems (at least one of which is aromatic) of 5-20 atoms, containing one or more heteroatoms independently selected from nitrogen, oxygen, and sulfur. Examples of heteroaryl groups are pyridinyl (including, for example, 2- hydroxypyridinyl), imidazolyl, imidazopyridinyl, 1-methyl-1H-benzo[d]imidazole, [1,2,4]triazolo[1,5-a]pyridine, pyrimidinyl (including, for example, 4-hydroxypyrimidinyl), pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxadiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, and furopyridinyl. Heteroaryl groups are optionally substituted independently with one or more substituents described herein. The heterocycle or heteroaryl groups may be carbon (carbon-linked), or nitrogen (nitrogen-linked) bonded where such is possible. By way of example and not limitation, carbon bonded heterocycles or heteroaryls are bonded at position 2, 3, 4, 5, or 6 of a pyridine, position 3, 4, 5, or 6 of a pyridazine, position 2, 4, 5, or 6 of a pyrimidine, position 2, 3, 5, or 6 of a pyrazine, position 2, 3, 4, or 5 of a furan, tetrahydrofuran, thiofuran, thiophene, pyrrole or tetrahydropyrrole, position 2, 4, or 5 of an oxazole, imidazole or thiazole, position 3, 4, or 5 of an isoxazole, pyrazole, or isothiazole, position 2 or 3 of an aziridine, position 2, 3, or 4 of an azetidine, position 2, 3, 4, 5, 6, 7, or 8 of a quinoline or position 1, 3, 4, 5, 6, 7, or 8 of an isoquinoline. By way of example and not limitation, nitrogen bonded heterocycles or heteroaryls are bonded at position 1 of an aziridine, azetidine, pyrrole, pyrrolidine, 2-pyrroline, 3- pyrroline, imidazole, imidazolidine, 2-imidazoline, 3-imidazoline, pyrazole, pyrazoline, 2- pyrazoline, 3-pyrazoline, piperidine, piperazine, indole, indoline, 1H-indazole, position 2 of a isoindole, or isoindoline, position 4 of a morpholine, and position 9 of a carbazole, or β- carboline. The term “chiral” refers to molecules which have the property of non- superimposability of the mirror image partner, while the term “achiral” refers to molecules which are superimposable on their mirror image partner. The term “stereoisomers” refers to compounds which have identical chemical constitution, but differ with regard to the arrangement of the atoms or groups in space. “Diastereomer” refers to a stereoisomer with two or more centers of chirality and whose molecules are not mirror images of one another. Diastereomers have different physical properties, e.g. melting points, boiling points, spectral properties, and reactivities. Mixtures of diastereomers may separate under high resolution analytical procedures such as electrophoresis and chromatography. “Enantiomers” refer to two stereoisomers of a compound which are non- superimposable mirror images of one another. The following definitions are used, unless otherwise described: halo or halogen is fluoro, chloro, bromo, or iodo. Alkyl and alkoxy, etc. denote both straight and branched groups but reference to an individual radical such as propyl embraces only the straight chain radical (a branched chain isomer such as isopropyl being specifically referred to). As used herein, the term "(Ca-Cb)alkyl" wherein a and b are integers refers to a straight or branched chain alkyl radical having from a to b carbon atoms. Thus when a is 1 and b is 6, for example, the term includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl and n-hexyl. The term “amino nitrogen protecting group” (P) refers to any protecting group (e.g., a BOC group) that can protect the amine groups during synthetic processes. Specific values listed below for radicals, substituents, and ranges, are for illustration only; they do not exclude other defined values or other values within defined ranges for the radicals and substituents. Specifically, (C1-C6)alkyl can be methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl, pentyl, 3-pentyl, hexyl. Stereochemical definitions and conventions used herein generally follow S. P. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., Stereochemistry of Organic Compounds (1994) John Wiley & Sons, Inc., New York. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L, or R and S, are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these stereoisomers are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric mixture. A 50:50 mixture of enantiomers is referred to as a racemic mixture or a racemate, which may occur where there has been no stereoselection or stereospecificity in a chemical reaction or process. The terms “racemic mixture” and “racemate” refer to an equimolar mixture of two enantiomeric species, devoid of optical activity. The phrase “pharmaceutically acceptable salt,” as used herein, refers to pharmaceutically acceptable organic or inorganic salts of an antibody-drug conjugate (ADC). Exemplary salts include, but are not limited, to sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, acid phosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucuronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and pamoate (i.e., 1,1’-methylene-bis -(2-hydroxy-3- naphthoate)) salts. A pharmaceutically acceptable salt may involve the inclusion of another molecule such as an acetate ion, a succinate ion or other counterion. The counterion may be any organic or inorganic moiety that stabilizes the charge on the parent compound. Furthermore, a pharmaceutically acceptable salt may have more than one charged atom in its structure. Instances where multiple charged atoms are part of the pharmaceutically acceptable salt can have multiple counter ions. Hence, a pharmaceutically acceptable salt can have one or more charged atoms and / or one or more counterion. The following abbreviations are used herein and have the indicated definitions: BME is beta-mercaptoethanol, Boc is N-(t-butoxycarbonyl), cit is citrulline (2-amino-5-ureido pentanoic acid), DCC is 1,3-dicyclohexylcarbodiimide, DCM is dichloromethane, DEA is diethylamine, DEAD is diethylazodicarboxylate, DEPC is diethylphosphorylcyanidate, DIAD is diisopropylazodicarboxylate, DIEA is N,N-diisopropylethylamine, DMA is dimethylacetamide, DMAP is 4-dimethylaminopyridine, DME is ethyleneglycol dimethyl ether (or 1,2-dimethoxyethane), DMF is N,N-dimethylformamide, DMSO is dimethylsulfoxide, DTT is dithiothreitol, EDCI is 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride, EEDQ is 2-ethoxy-1-ethoxycarbonyl-1,2- dihydroquinoline, ES-MS is electrospray mass spectrometry, EtOAc is ethyl acetate, Fmoc is N-(9-fluorenylmethoxycarbonyl), gly is glycine, HATU is O-(7-azabenzotriazol-1-yl)- N,N,N’,N’-tetramethyluronium hexafluorophosphate, HOBt is 1-hydroxybenzotriazole, HPLC is high pressure liquid chromatography, ile is isoleucine, lys is lysine, MeCN (CH3CN) is acetonitrile, MeOH is methanol, Mtr is 4-anisyldiphenylmethyl (or 4- methoxytrityl), NHS is N-hydroxysuccinimide, PBS is phosphate-buffered saline (pH 7), PEG is polyethylene glycol or a unit of ethylene glycol (-OCH2CH2-), Ph is phenyl, Pnp is p- nitrophenyl, MC is 6-maleimidocaproyl, phe is L-phenylalanine, PyBrop is bromo tris- pyrrolidino phosphonium hexafluorophosphate, SEC is size-exclusion chromatography, Su is succinimide, TFA is trifluoroacetic acid, TLC is thin layer chromatography, UV is ultraviolet, and val is valine. Antibody Unit (Ab or AB) As noted above, the term “antibody” (or “Ab” or “AB”) herein is used in the broadest sense and specifically covers intact monoclonal antibodies, polyclonal antibodies, monospecific antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments that exhibit the desired biological activity. Accordingly, the term “antibody” includes antibody fragment thereof and thus is used interchangeably with the term “antibody or fragment thereof”. In addition, while certain aspects of the invention described herein refer to antibody-drug conjugates, it is further envisioned that the antibody portion of the conjugate might be replaced with anything that specifically binds or reactively associates or complexes with a receptor, antigen or other receptive moiety associated with a given target-cell population. For example, instead of containing an antibody a conjugate of the invention could contain a targeting molecule (also referred to as a binding agent) that binds to, complexes with, or reacts with a receptor, antigen or other receptive moiety of a cell population sought to be therapeutically or otherwise biologically modified. Example of such molecules include smaller molecular weight proteins, polypeptide or peptides, lectins, glycoproteins, non- peptides, vitamins, nutrient-transport molecules (such as, but not limited to, transferrin), or any other cell binding molecule or substances. In certain aspects, the antibody or other such targeting molecule acts to deliver a drug to the particular target cell population with which the antibody or other targeting molecule interacts. In another aspect, the present invention relates to an antibody-drug conjugate compound wherein the antibody AB is selected from: gemtuzumab, trastuzumab (Herceptin®), pertuzumab (Perjeta®), iratumumab, inotuzumab, pinatuzumab, epratuzumab, polatuzumab, coltuximab, lovotuzumab, sacituzumab, anetumab, aprutumab, aratumumab, atezolizumab, avelumab, azintuxizumab, bevacizumab (Avastin®), bivatuzumab, brentuximab, camidanlumab, cantuzumab, cetuximab (Erbitux®), cofetuzumab, denintuzumab, durvalumab, elotuzumab, enfortumab, glembatumumab, ibritumomab, iladatuzumab, indatuximab, industuzumab, labetuzumab, ladiratuzumab, laprituximab, lifastuzumab, loncastuximab, lorvotuzumab, lupartumab, milatuzumab, mirvetuximab, naratuximab, natalizumab, necitumumab, obinutuzumab, ocrelizumab, ofatumumab, olaratumab, panitumumab, pertuzumab, rituximab (Rituxan®), rovalpituzumab, sirtratumab, sofituzumab, telisotuzumab, tositumomab, trastuzumab, and vadastuximab. In certain embodiments, the antibody AB is selected from the group consisting of: trastuzumab, pertuzumab, gemtuzumab, and vadastuximab. In another aspect, the present invention relates to an antibody-drug conjugate compound wherein the antibody AB is selected from: gemtuzumab, trastuzumab (Herceptin®), pertuzumab (Perjeta®), iratumumab, inotuzumab, pinatuzumab, enapotamab, epratuzumab, polatuzumab, coltuximab, lovotuzumab, sacituzumab, anetumab, aprutumab, aratumumab, atezolizumab, avelumab, azintuxizumab, bevacizumab (Avastin®), belantamab, bivatuzumab, brentuximab, camidanlumab, cantuzumab, cetuximab (Erbitux®), cofetuzumab, datopotamab, depatuxizumab, denintuzumab, disatamab, durvalumab, elotuzumab, enfortumab, farletuzumab, gemtuzumab, glembatumumab, ibritumomab, ifinatamab, iladatuzumab, indatuximab, industuzumab, indusatumab, labetuzumab, ladiratuzumab, laprituximab, lifastuzumab, loncastuximab, lorvotuzumab, lupartumab, luveltamab, milatuzumab, mirvetuximab, mecbotamab, moxetumomab, naratuximab, natalizumab, necitumumab, obinutuzumab, ocrelizumab, ofatumumab, olaratumab, opelkibart, ozuriftamab, panitumumab, patritumab, praluzatamab, rituximab (Rituxan®), Raludotatug, rovalpituzumab, sirtratumab, sigvotatugum, sofituzumab, telisotuzumab, tisotumab, tositumomab, trastuzumab, tusamitamab,vadastuximab, vobramitamab, vorsetuzumab, zilovertamab and zalontamab. In certain embodiments, the antibody AB is selected from the group consisting of: trastuzumab, pertuzumab, gemtuzumab, and vadastuximab. Heteroatoms that may be present on an antibody unit include sulfur (in one embodiment, from a sulfhydryl group of an antibody), oxygen (in one embodiment, from a carbonyl, carboxyl or hydroxyl group of an antibody) and nitrogen (in one embodiment, from a primary or secondary amino group of an antibody). These hetero atoms can be present on the antibody in the antibody's natural state, or can be introduced into the antibody via chemical modification. In one embodiment, an antibody unit has a sulfhydryl group and the antibody unit bonds via the sulfhydryl group's sulfur atom. In another embodiment, the antibody has lysine residues that can react with activated esters (such esters include, but are not limited to, N-hydroxysuccinimde, pentafluorophenyl, and p-nitrophenyl esters) and thus form an amide bond consisting of the nitrogen atom of the antibody unit and a carbonyl. In another embodiment the activated esters include N- hydroxysuccinimide and phenyl esters (-C(=O)OPh) wherein the phenyl is optionally substituted with one or more fluoro, chloro, bromo, iodo, or nitro. In yet another aspect, the antibody unit has one or more lysine residues that can be chemically modified to introduce one or more sulfhydryl groups. The reagents that can be used to modify lysines include, but are not limited to, N-hydroxysuccinimide acetate ester (NHS ester), N-succinimidyl S-acetylthioacetate (SATA), and 2-Iminothiolane hydrochloride (Traut's Reagent). In another embodiment, the antibody unit can have one or more carbohydrate groups that can be chemically modified to have one or more sulfhydryl groups. In yet another embodiment, the antibody unit can have one or more carbohydrate groups that can be oxidized to provide an aldehyde group. The corresponding aldehyde can form a bond with a reactive site such as, for example, hydrazine and hydroxylamine. Other protocols for the modification of proteins for the attachment or association of drugs are described in Coligan et al., Current Protocols in Protein Science, Vol.2, John Wiley & Sons (2002). Useful polyclonal antibodies are heterogeneous populations of antibody molecules derived from the sera of immunized animals. Useful monoclonal antibodies are homogeneous populations of antibodies to a particular antigenic determinant (e.g., a cancer cell antigen, a viral antigen, a microbial antigen, a protein, a peptide, a carbohydrate, a chemical, nucleic acid, or fragments thereof). A monoclonal antibody (mAb) to an antigen- of-interest can be prepared by using any technique known in the art which provides for the production of antibody molecules by continuous cell lines in culture. Useful monoclonal antibodies include, but are not limited to, human monoclonal antibodies, humanized monoclonal antibodies, antibody fragments, or chimeric monoclonal antibodies. Human monoclonal antibodies may be made by any of numerous techniques known in the art. The antibody can also be a bispecific antibody. Methods for making bispecific antibodies are known in the art. The antibody can be a functionally active fragment, derivative or analog of an antibody that immunospecifically binds to target cells (e.g., tumor-associated antigens, cancer cell antigens, viral antigens, or microbial antigens) or other antibodies that bind to tumor cells or matrix. The “functionally active” fragment, derivative or analog is capable of binding the same antigen / epitope as the intact antibody. In certain embodiments, “functionally active” fragment, derivative or analog is able to elicit anti-anti-idiotype antibodies that recognize the same antigen that the antibody from which the fragment, derivative or analog is derived recognized. Specifically, in an exemplary embodiment the antigenicity of the idiotype of the immunoglobulin molecule can be enhanced by deletion of framework and CDR sequences that are C-terminal to the CDR sequence that specifically recognizes the antigen. To determine which CDR sequences bind the antigen, synthetic peptides containing the CDR sequences can be used in binding assays with the antigen by any binding assay method known in the art (e.g., the BIA core assay). Other useful antibodies include fragments of antibodies such as, but not limited to, F(ab′)2fragments, Fab fragments, single chain antibodies, diabodies, triabodies, tetrabodies, scFv, scFv-Fc, or any other molecule with the same specificity as the antibody. Additionally, recombinant antibodies, such as chimeric and humanized monoclonal antibodies, comprising both human and non-human portions, which can be made using standard recombinant DNA techniques, are useful antibodies. A chimeric antibody is a molecule in which different portions are derived from different animal species, such as for example, those having a variable region derived from a murine monoclonal and human immunoglobulin constant regions. Humanized antibodies are antibody molecules from non- human species having one or more complementarity determining regions (CDRs) from the non-human species and a framework region from a human immunoglobulin molecule. Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques known in the art. Completely human antibodies are particularly desirable and can be produced using transgenic mice that are incapable of expressing endogenous immunoglobulin heavy and light chains genes, but which can express human heavy and light chain genes. The transgenic mice are immunized in the normal fashion with a selected antigen, e.g., to produce all or a portion of a polypeptide of the invention. Monoclonal antibodies directed against the antigen can be obtained using conventional hybridoma technology. The human immunoglobulin transgenes harbored by the transgenic mice rearrange during B cell differentiation, and subsequently undergo class switching and somatic mutation. Thus, using such a technique, it is possible to produce therapeutically useful IgG, IgA, IgM and IgE antibodies using methods known to one skilled in the art. Other human antibodies can be obtained commercially from numerous companies. Completely human antibodies that recognize a selected epitope can be generated using a technique referred to as “guided selection.” In this approach a selected non-human monoclonal antibody, e.g., a mouse antibody, is used to guide the selection of a completely human antibody recognizing the same epitope. Human antibodies can also be produced using various techniques known in the art, including phage display libraries. In other embodiments, the antibody is a fusion protein of an antibody, or a functionally active fragment thereof, for example in which the antibody is fused via a covalent bond (e.g., a peptide bond), at either the N-terminus or the C-terminus to an amino acid sequence of another protein (or portion thereof, preferably at least 10, 20 or 50 amino acid portion of the protein) that is not from an antibody. Antibodies include analogs and derivatives that are either modified, i.e., by the covalent attachment of any type of molecule as long as such covalent attachment permits the antibody to retain its antigen binding immunospecificity. For example, but not by way of limitation, derivatives and analogs of the antibodies include those that have been further modified, e.g., by glycosylation, acetylation, pegylation, phosphorylation, amidation, derivatization by known protecting / blocking groups, proteolytic cleavage, linkage to a cellular antibody unit or other protein, etc. Any of numerous chemical modifications can be carried out by known techniques including, but not limited to, specific chemical cleavage, acetylation, formylation, metabolic synthesis in the presence of tunicamycin, etc. Additionally, the analog or derivative can contain one or more unnatural amino acids. Antibodies can have modifications (e.g., substitutions, deletions or additions) in amino acid residues that interact with Fc receptors. In particular, antibodies can have modifications in amino acid residues identified as involved in the interaction with the FcRn receptor. Antibodies immunospecific for a cancer cell antigen can be obtained commercially or produced by any method known to one of skill in the art such as, e.g., chemical synthesis or recombinant expression techniques. The nucleotide sequence encoding antibodies immunospecific for a cancer cell antigen can be obtained, e.g., from the GenBank database or a database like it, literature publications, or by routine cloning and sequencing. In a specific embodiment, known antibodies for the treatment of cancer can be used. Antibodies immunospecific for a cancer cell antigen can be obtained commercially or produced by any method known to one of skill in the art such as, e.g., recombinant expression techniques. The nucleotide sequence encoding antibodies immunospecific for a cancer cell antigen (tumor-associated antigens) can be obtained, e.g., from the GenBank database or a database like it, the literature publications, or by routine cloning and sequencing. Examples of tumor-associated antigens (TAA) include, but are not limited to, TAA (1)-(100) listed herein. For convenience, in most cases, information relating to these antigens, all of which are known in the art, is listed herein and includes, in most cases, names, alternative names, GenBank accession numbers and primary reference(s), following nucleic acid and protein sequence identification conventions of the National Center for Biotechnology Information (NCBI). Nucleic acid and protein sequences corresponding to TAA (1)-(100) are available in public databases such as GenBank. Tumor-associated antigens targeted by antibodies include all amino acid sequence variants and isoforms possessing at least about 70%, 80%, 85%, 90%, or 95% sequence identity relative to the sequences identified in the cited references, or which exhibit substantially the same biological properties or characteristics as a TAA having a sequence found in the cited references. For example, a TAA having a variant sequence generally is able to bind specifically to an antibody that binds specifically to the TAA with the corresponding sequence listed. The sequences and disclosure in the reference specifically recited herein are expressly incorporated by reference. Specific non-limiting examples of TAA include: (1) BMPR1B (bone morphogenetic protein receptor-type IB, GenBank accession no. NM_001203); ten Dijke, P., et al., Science, 1994, 264 (5155):101-104; Oncogene, 1997, 14(11):1377-1382); WO 2004 / 063362 (Claim 2); WO 2003 / 042661 (Claim 12); US 2003 / 134790 (Page 38-39); WO 2002 / 102235 (Claim 13; Page 296); WO 2003 / 055443 (Page 91-92); WO 2002 / 99122 (Example 2; Page 528-530); WO 2003 / 029421 (Claim 6); WO 2003 / 024392 (Claim 2; Fig 112); WO 2002 / 98358 (Claim 1; Page 183); WO 2002 / 54940 (Page 100-101); WO 2002 / 59377(Page 349-350); WO 2002 / 30268 (Claim 27; Page 376); WO 2001 / 48204 (Example; Fig 4) NP_001194 bone morphogenetic protein receptor, type IB / pid=NP_001194.1 - Cross-references: MIM:603248; NP_001194.1; AY065994. (2) E16 (LAT1, SLC7A5, GenBank accession no. NM_003486); Biochem. Biophys. Res. Commun., 1999, 255(2), 283-288; Nature, 1998, 395(6699):288-291; Gaugitsch, H.W., et al., J. Biol. Chem., 1992, 267(16):11267-11273); WO 2004 / 048938 (Example 2); WO 2004 / 032842 (Example IV); WO 2003 / 042661 (Claim 12); WO 2003 / 016475 (Claim 1); WO 2002 / 78524 (Example 2); WO 2002 / 99074 (Claim 19; Page 127-129); WO 2002 / 86443 (Claim 27; Pages 222, 393); WO 2003 / 003906 (Claim 10; Page 293); WO 2002 / 64798 (Claim 33; Page 93-95); WO 2000 / 14228 (Claim 5; Page 133-136); US 2003 / 224454 (Fig 3); WO 2003 / 025138 (Claim 12; Page 150); NP_003477 solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 / pid=NP_003477.3 - Homo sapiens Cross-references: MIM:600182; NP_003477.3; NM_015923; NM_003486_1. (3) STEAP1 (six transmembrane epithelial antigen of prostate, GenBank accession no. NM_012449); Cancer Res., 2001, 61(15), 5857-5860; Hubert, R.S., et al., Proc. Natl. Acad. Sci. U.S.A., 96 (25):14523-14528); WO 2004 / 065577 (Claim 6); WO 2004 / 027049 (Fig 1L); EP 1394274 (Example 11); WO 2004 / 016225 (Claim 2); WO 2003 / 042661 (Claim 12); US 2003 / 157089 (Example 5); US 2003 / 185830 (Example 5); US 2003 / 064397 (Fig 2); WO 2002 / 89747 (Example 5; Page 618-619); WO 2003 / 022995 (Example 9; Fig 13A, Example 53; Page 173, Example 2; Fig 2A); NP_036581 six transmembrane epithelial antigen of the prostate Cross-references: MIM:604415; NP_036581.1; NM_012449_1. (4) 0772P (CA125, MUC16, GenBank accession no. AF361486); J. Biol. Chem., 2001, 276(29):27371-27375; WO 2004 / 045553 (Claim 14); WO 2002 / 92836 (Claim 6; Fig 12); WO 2002 / 83866 (Claim 15; Page 116-121); US 2003 / 124140 (Example 16). Cross-references: GI:34501467; AAK74120.3; AF361486_1. (5) MPF (MPF, MSLN, SMR, megakaryocyte potentiating factor, mesothelin, GenBank accession no. NM_005823); Yamaguchi, N., et al., Biol. Chem., 1994, 269(2), 805- 808; Proc. Natl. Acad. Sci. U.S.A., 1999, 96(20):11531-11536; Proc. Natl. Acad. Sci. U.S.A., 1996, 93(1):136-140; J. Biol. Chem., 1995, 270(37):21984-21990; WO 2003 / 101283 (Claim 14); (WO 2002 / 102235 (Claim 13; Page 287-288); WO 2002 / 101075 (Claim 4; Page 308- 309); WO 2002 / 71928 (Page 320-321); WO 9410312 (Page 52-57); Cross-references: MIM:601051; NP_005814.2; NM_005823_1. (6) Napi3b (NAPI-3B, NPTIIb, SLC34A2, solute carrier family 34 (sodium phosphate), member 2, type II sodium-dependent phosphate transporter 3b, GenBank accession no. NM_006424); J. Biol. Chem., 2002, 277(22):19665-19672; Genomics, 1999, 62(2):281-284; Feild, J.A., et al., Biochem. Biophys. Res. Commun., 1999, 258(3):578-582); WO 2004 / 022778 (Claim 2); EP 1394274 (Example 11); WO 2002 / 102235 (Claim 13; Page 326); EP 875569 (Claim 1; Page 17-19); WO 2001 / 57188 (Claim 20; Page 329); WO 2004 / 032842 (Example IV); WO200175177 (Claim 24; Page 139-140); Cross-references: MIM:604217; NP_006415.1; NM_006424_1. (7) Sema 5b (FLJ10372, KIAA1445, Mm.42015, SEMA5B, SEMAG, Semaphorin 5b Hlog, sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5B, GenBank accession no. AB040878); Nagase T., et al., DNA Res., 2000, 7(2):143-150); WO 2004 / 000997 (Claim 1); WO 2003 / 003984 (Claim 1); WO 2002 / 06339 (Claim 1; Page 50); WO 2001 / 88133 (Claim 1; Page 41-43, 48-58); WO 2003 / 054152 (Claim 20); WO 20031 / 01400 (Claim 11); Accession: Q9P283; EMBL; AB040878; BAA95969.1. Genew; HGNC:10737. (8) PSCA hlg (2700050C12Rik, C530008O16Rik, RIKEN cDNA 2700050C12, RIKEN cDNA 2700050C12 gene, GenBank accession no. AY358628); Ross et al., Cancer Res., 2002, 62:2546-2553; US 2003 / 129192 (Claim 2); US 2004 / 044180 (Claim 12); US 2004 / 044179 (Claim 11); US 2003 / 096961 (Claim 11); US 2003 / 232056 (Example 5); WO 2003 / 105758 (Claim 12); US 2003 / 206918 (Example 5); EP 1347046 (Claim 1); WO 2003 / 025148 (Claim 20); Cross-references: GI:37182378; AAQ88991.1; AY358628_1. (9) ETBR (Endothelin type B receptor, GenBank accession no. AY275463); Nakamuta M., et al., Biochem. Biophys. Res. Commun., 1991, 177:34-39; Ogawa Y., et al., Biochem. Biophys. Res. Commun., 1991, 178, 248-255; Arai, H., et al., Jpn. Circ. J., 1992, 56:1303-1307; Arai, H., et al., J. Biol. Chem., 1993, 268:3463-3470; Sakamoto A., Yanagisawa M., et al., Biochem. Biophys. Res. Commun., 1991, 178:656-663; Elshourbagy N.A., et al., J. Biol. Chem., 1993, 268:3873-3879; Haendler B., et al., J. Cardiovasc. Pharmacol., 1992, 20:s1-S4; Tsutsumi M., et al., Gene, 1999, 228:43-49; Strausberg, R.L., et al., Proc. Natl. Acad. Sci. U.S.A., 2002, 99:16899-16903; Bourgeois C., et al., J. Clin. Endocrinol. Metab., 1997, 82, 3116-3123; Okamoto Y., et al., Biol. Chem., 1997, 272:21589- 21596; Verheij, J.B., Am. J. Med. Genet., 2002, 108:223-225; Hofstra, R.M.W., et al., Eur. J. Hum. Genet., 1997, 5:180-185; Puffenberger, E.G., et al., Cell, 1994, 79:1257-1266; Attie T., et al., Hum. Mol. Genet., 1995, 4:2407-2409; Auricchio A., et al., Hum. Mol. Genet., 1996, 5:351-354; Amiel J., et al. Hum. Mol. Genet.5, 355-357, 1996; Hofstra R.M.W., et al. Nat. Genet., 1996, 12:445-447; Svensson, P.J., et al., Hum. Genet., 1998, 103:145-148; Fuchs, S., et al., Mol. Med., 2001, 7:115-124; Pingault V., et al., Hum. Genet., 2002, 111:198-206; WO 2004 / 045516 (Claim 1); WO 2004 / 048938 (Example 2); WO 2004 / 040000 (Claim 151); WO 2003 / 087768 (Claim 1); WO 2003 / 016475 (Claim 1); WO 2003 / 016475 (Claim 1); WO 2002 / 61087 (Fig 1); WO 2003 / 016494 (Fig 6); WO 2003 / 025138 (Claim 12; Page 144); WO 2001 / 98351 (Claim 1; Page 124-125); EP 522868 (Claim 8; Fig 2); WO 2001 / 77172 (Claim 1; Page 297-299); US 2003 / 109676; US 6,518,404 (Fig 3); US 5,773,223 (Claim 1a; Col 31- 34); WO 2004 / 001004. (10) MSG783 (RNF124, hypothetical protein FLJ20315, GenBank accession no. NM_017763); WO 2003 / 104275 (Claim 1); WO 2004 / 046342 (Example 2); WO 2003 / 042661 (Claim 12); WO 2003 / 083074 (Claim 14; Page 61); WO 2003 / 018621 (Claim 1); WO 2003 / 024392 (Claim 2; Fig 93); WO 2001 / 66689 (Example 6); Cross-references: LocusID:54894; NP_060233.2; NM_017763_1. (11) STEAP2 (HGNC_8639, IPCA-1, PCANAP1, STAMP1, STEAP2, STMP, prostate cancer associated gene 1, prostate cancer associated protein 1, six transmembrane epithelial antigen of prostate 2, six transmembrane prostate protein, GenBank accession no. AF455138) Lab. Invest.82 (11):1573-1582 (2002)); WO 2003 / 087306; US 2003 / 064397 (Claim 1; Fig 1); WO 2002 / 72596 (Claim 13; Page 54-55); WO 2001 / 72962 (Claim 1; Fig 4B); WO 2003 / 104270 (Claim 11); WO 2003 / 104270 (Claim 16); US 2004 / 005598 (Claim 22); WO 2003 / 042661 (Claim 12); US 2003 / 060612 (Claim 12; Fig 10); WO 2002 / 26822 (Claim 23; Fig 2); WO 2002 / 16429 (Claim 12; Fig 10); Cross-references: GI:22655488; AAN04080.1; AF455138_1. (12) TrpM4 (BR22450, FLJ20041, TRPM4, TRPM4B, transient receptor potential cation channel, subfamily M, member 4, GenBank accession no. NM_017636) Xu, X.Z., et al., Proc. Natl. Acad. Sci. U.S.A., 2001, 98(19):10692-10697; Cell, 2002, 109(3):397- 407; J. Biol. Chem., 2003, 278(33):30813-30820; US 2003 / 143557 (Claim 4); WO 2000 / 40614 (Claim 14; Page 100-103); WO 2002 / 10382 (Claim 1; Fig 9A); WO 2003 / 042661 (Claim 12); WO 2002 / 30268 (Claim 27; Page 391); US 2003 / 219806 (Claim 4); WO 2001 / 62794 (Claim 14; Fig 1A-D); Cross-references: MIM:606936; NP_060106.2; NM_017636_1. (13) CRIPTO (CR, CR1, CRGF, CRIPTO, TDGF1, teratocarcinoma-derived growth factor, GenBank accession no. NP_003203 or NM_003212); Ciccodicola, A., et al., EMBO J., 1989, 8(7):1987-1991; Am. J. Hum. Genet., 1991, 49(3):555-565; US 2003 / 224411 (Claim 1); WO 2003 / 083041 (Example 1); WO 2003 / 034984 (Claim 12); WO 2002 / 88170 (Claim 2; Page 52-53); WO 2003 / 024392 (Claim 2; Fig 58); WO 2002 / 16413 (Claim 1; Page 94-95, 105); WO 2002 / 22808 (Claim 2; Fig 1); US 5,854,399 (Example 2; Col 17-18); US 5,792,616 (Fig 2); Cross-references: MIM:187395; NP_003203.1; NM_003212_1. (14) CD21 (CR2 (Complement receptor 2) or C3DR (C3d / Epstein Barr virus receptor) or Hs.73792 GenBank accession no. M26004); Fujisaku, et al., J. Biol. Chem., 1989, 264(4):2118-2125); Weis J.J., et al., J. Exp. Med., 1988, 167:1047-1066; Moore M., et al., Proc. Natl. Acad. Sci. U.S.A., 1987, 84:9194-9198; Barel M., et al., Mol. Immunol., 1998, 35:1025-1031; Weis J.J., et al., Proc. Natl. Acad. Sci. U.S.A., 1986, 83:5639-5643; Sinha S.K., et al., J. Immunol., 1993, 150:5311-5320; WO 2004 / 045520 (Example 4); US 2004 / 005538 (Example 1); WO 2003 / 062401 (Claim 9); WO 2004 / 045520 (Example 4); WO 9102536 (Fig 9.1-9.9); WO 2004 / 020595 (Claim 1); Accession: P20023; Q13866; Q14212; EMBL; M26004; AAA35786.1. (15) CD79b (CD79B, CD79β, IGb (immunoglobulin-associated beta), B29, GenBank accession no. NM_000626 or 11038674); Proc. Natl. Acad. Sci. U.S.A., 2003, 100(7):4126-4131; Blood, 2002, 100(9):3068-3076; Muller, et al., Eur. J. Immunol., 1992, 22(6):1621-1625; WO 2004 / 016225 (claim 2, Fig 140); WO 2003 / 087768, US 2004 / 101874 (claim 1, page 102); WO 2003 / 062401 (claim 9); WO 2002 / 78524 (Example 2); US 2002 / 150573 (claim 5, page 15); US 5,644,033; WO 2003 / 048202 (claim 1, pages 306 and 309); WO 99 / 558658, US 6,534,482 (claim 13, Fig 17A / B); WO 2000 / 55351 (claim 11, pages 1145-1146); Cross-references: MIM:147245; NP_000617.1; NM_000626_1. (16) FcRH2 (IFGP4, IRTA4, SPAP1A (SH2 domain containing phosphatase anchor protein 1a), SPAP1B, SPAP1C, GenBank accession no. NM_030764, AY358130); Genome Res., 2003, 13(10):2265-2270; Immunogenetics, 2002, 54(2):87-95; Blood, 2002, 99(8):2662-2669; Proc. Natl. Acad. Sci. U.S.A., 2001, 98(17):9772-9777; Xu, M.J., et al., Biochem. Biophys. Res. Commun., 2001, 280(3):768-775; WO 2004 / 016225 (Claim 2); WO 2003 / 077836; WO 2001 / 38490 (Claim 5; Fig 18D-1-18D-2); WO 2003 / 097803 (Claim 12); WO 2003 / 089624 (Claim 25); Cross-references: MIM:606509; NP_110391.2; NM_030764_1. (17) HER2 (ErbB2, GenBank accession no. M11730); Coussens, L., et al., Science, 1985, 230(4730):1132-1139); Yamamoto, T., et al., Nature, 1986, 319:230-234; Semba, K., et al., Proc. Natl. Acad. Sci. U.S.A., 1985, 82:6497-6501; Swiercz, J.M., et al., J. Cell Biol., 2004, 165:869-880; Kuhns, J.J., et al., J. Biol. Chem., 1999, 274:36422-36427; Cho H.-S., et al., Nature, 1993, 421:756-760; Ehsani, A., et al., Genomics, 1993, 15:426-429; WO 2004 / 048938 (Example 2); WO 2004 / 027049 (Fig 1I); WO 2004 / 009622; WO 2003 / 081210; WO 2003 / 089904 (Claim 9); WO 2003 / 016475 (Claim 1); US 2003 / 118592; WO 2003 / 008537 (Claim 1); WO 2003 / 055439 (Claim 29; Fig 1A-B); WO 2003 / 025228 (Claim 37; Fig 5C); WO 2002 / 22636 (Example 13; Page 95-107); WO 2002 / 12341 (Claim 68; Fig 7); WO 2002 / 13847 (Page 71-74); WO 2002 / 14503 (Page 114-117); WO 2001 / 53463 (Claim 2; Page 41-46); WO 2001 / 41787 (Page 15); WO 2000 / 44899 (Claim 52; Fig 7); WO 2000 / 20579 (Claim 3; Fig 2); US 5,869,445 (Claim 3; Col 31-38); WO 9630514 (Claim 2; Page 56-61); EP 1439393 (Claim 7); WO 2004 / 043361 (Claim 7); WO 2004 / 022709; WO 2001 / 00244 (Example 3; Fig 4); Accession: P04626; EMBL; M11767; AAA35808.1. EMBL; M11761; AAA35808.1. (18) NCA (CEACAM6, GenBank accession no. M18728); Barnett T., et al., Genomics, 1988, 3:59-66; Tawaragi, Y., et al., Biochem. Biophys. Res. Commun., 1988, 150:89-96; Strausberg, R.L., et al. Proc. Natl. Acad. Sci. U.S.A., 2002, 99:16899-16903; WO 2004 / 063709; EP 1439393 (Claim 7); WO 2004 / 044178 (Example 4); WO 2004 / 031238; WO 2003 / 042661 (Claim 12); WO 2002 / 78524 (Example 2); WO 2002 / 86443 (Claim 27; Page 427); WO 2002 / 60317 (Claim 2); Accession: P40199; Q14920; EMBL; M29541; AAA59915.1. EMBL; M18728. (19) MDP (DPEP1, GenBank accession no. BC017023); Proc. Natl. Acad. Sci. U.S.A., 2002, 99(26):16899-16903; WO 2003 / 016475 (Claim 1); WO 2002 / 64798 (Claim 33; Page 85-87); JP 05003790 (Fig 6-8); WO 9946284 (Fig 9); Cross-references: MIM:179780; AAH17023.1; BC017023_1. (20) IL20Rα (IL20Ra, ZCYTOR7, GenBank accession no. AF184971); Clark H.F., et al., Genome Res., 2003, 13:2265-2270; Mungall A.J., et al., Nature, 2003, 425:805- 811; Blumberg H., et al., Cell, 2001, 104:9-19; Dumoutier L., et al., J. Immunol., 2001, 167:3545-3549; Parrish-Novak J., et al., J. Biol. Chem., 2002, 277:47517-47523; Pletnev, S., et al., Biochemistry, 2003, 42:12617-12624; Sheikh F., et al., J. Immunol., 2004, 172:2006- 2010; EP 1394274 (Example 11); US 2004 / 005320 (Example 5); WO 2003 / 029262 (Page 74- 75); WO 2003 / 002717 (Claim 2; Page 63); WO 2002 / 22153 (Page 45-47); US 2002 / 042366 (Page 20-21); WO 2001 / 46261 (Page 57-59); WO 2001 / 46232 (Page 63-65); WO 9837193 (Claim 1; Page 55-59); Accession: Q9UHF4; Q6UWA9; Q96SH8; EMBL; AF184971; AAF01320.1. (21) Brevican (BCAN, BEHAB, GenBank accession no. AF229053); Gary S.C., et al., Gene, 2000, 256:39-147; Clark H.F., et al., Genome Res., 2003, 13:2265-2270; Strausberg, R.L., et al. Proc. Natl. Acad. Sci. U.S.A., 2002, 99:16899-16903; US 2003 / 186372 (Claim 11); US 2003 / 186373 (Claim 11); US 2003 / 119131 (Claim 1; Fig 52); US 2003 / 119122 (Claim 1; Fig 52); US 2003 / 119126 (Claim 1); US 2003 / 119121 (Claim 1; Fig 52); US 2003 / 119129 (Claim 1); US 2003 / 119130 (Claim 1); US 2003 / 119128 (Claim 1; Fig 52); US 2003 / 119125 (Claim 1); WO 2003 / 016475 (Claim 1); WO 2002 / 02634 (Claim 1). (22) EphB2R (DRT, ERK, Hek5, EPHT3, Tyro5, GenBank accession no. NM_004442) Chan, J. and Watt, V.M., Oncogene, 1991, 6(6): 1057-1061; Oncogene, 1995, 10(5):897-905; Annu. Rev. Neurosci., 1998, 21:309-345; Int. Rev. Cytol., 2000, 196:177-244; WO 2003 / 042661 (Claim 12); WO 2000 / 53216 (Claim 1; Page 41); WO 2004 / 065576 (Claim 1); WO 2004 / 020583 (Claim 9); WO 2003 / 004529 (Page 128-132); WO 2000 / 53216 (Claim 1; Page 42); Cross-references: MIM:600997; NP_004433.2; NM_004442_1. (23) ASLG659 (B7h, GenBank accession no. AX092328) US20040101899 (Claim 2); WO 2003 / 104399 (Claim 11); WO 2004 / 000221 (Fig 3); US 2003 / 165504 (Claim 1); US 2003 / 124140 (Example 2); US 2003 / 065143 (Fig 60); WO 2002 / 102235 (Claim 13; Page 299); US 2003 / 091580 (Example 2); WO 2002 / 10187 (Claim 6; Fig 10); WO 2001 / 94641 (Claim 12; Fig 7b); WO 2002 / 02624 (Claim 13; Fig 1A-1B); US 2002 / 034749 (Claim 54; Page 45-46); WO 2002 / 06317 (Example 2; Page 320-321, Claim 34; Page 321- 322); WO 2002 / 71928 (Page 468-469); WO 2002 / 02587 (Example 1; Fig 1); WO 2001 / 40269 (Example 3; Pages 190-192); WO 2000 / 36107 (Example 2; Page 205-207); WO 2004 / 053079 (Claim 12); WO 2003 / 004989 (Claim 1); WO 2002 / 71928 (Page 233-234, 452- 453); WO 0116318. (24) PSCA (Prostate stem cell antigen precursor, GenBank accession no. AJ297436) Reiter R.E., et al., Proc. Natl. Acad. Sci. U.S.A., 1998, 95:1735-1740; Gu Z., et al., Oncogene, 2000, 19:1288-1296; Biochem. Biophys. Res. Commun., 2000, 275(3):783- 788; WO 20040 / 22709; EP 1394274 (Example 11); US 2004 / 018553 (Claim 17); WO 2003 / 008537 (Claim 1); WO 2002 / 81646 (Claim 1; Page 164); WO 2003 / 003906 (Claim 10; Page 288); WO 2001 / 40309 (Example 1; Fig 17); US 2001 / 055751 (Example 1; Fig 1b); WO 2000 / 32752 (Claim 18; Fig 1); WO 1998 / 51805 (Claim 17; Page 97); WO 1998 / 51824 (Claim 10; Page 94); WO 1998 / 40403 (Claim 2; Fig 1B); Accession: O43653; EMBL; AF043498; AAC39607.1. (25) GEDA (GenBank accession No. AY260763); AAP14954 lipoma HMGIC fusion-partner-like protein / pid=AAP14954.1 - Homo sapiens Species: Homo sapiens (human) WO 2003 / 054152 (Claim 20); WO 2003 / 000842 (Claim 1); WO 2003 / 023013 (Example 3, Claim 20); US 2003 / 194704 (Claim 45); Cross-references: GI:30102449; AAP14954.1; AY260763_1. (26) BAFF-R (B cell -activating factor receptor, BLyS receptor 3, BR3, GenBank accession No. AF116456); BAFF receptor / pid=NP_443177.1 - Homo sapiens Thompson, J.S., et al., Science, 2001, 293(5537):2108-2111; WO 2004 / 058309; WO 2004 / 011611; WO 2003 / 045422 (Example; Page 32-33); WO 2003 / 014294 (Claim 35; Fig 6B); WO 2003 / 035846 (Claim 70; Page 615-616); WO 2002 / 94852 (Col 136-137); WO 2002 / 38766 (Claim 3; Page 133); WO 2002 / 24909 (Example 3; Fig 3); Cross-references: MIM:606269; NP_443177.1; NM_052945_1; AF132600. (27) CD22 (B-cell receptor CD22-B isoform, BL-CAM, Lyb-8, Lyb8, SIGLEC-2, FLJ22814, GenBank accession No. AK026467); Wilson, et al., J. Exp. Med., 1991, 173:137-146; WO 2003 / 072036 (Claim 1; Fig 1); Cross-references: MIM:107266; NP_001762.1; NM_001771_1. (28) CD79a (CD79A, CD79α, immunoglobulin-associated alpha, a B cell- specific protein that covalently interacts with Ig beta (CD79B) and forms a complex on the surface with Ig M molecules, transduces a signal involved in B-cell differentiation), pI: 4.84, MW: 25028 TM: 2 [P] Gene Chromosome: 19q13.2, GenBank accession No. NP_001774.10) WO 2003 / 088808, US 2003 / 0228319; WO 2003 / 062401 (claim 9); US 2002 / 150573 (claim 4, pages 13-14); WO 9958658 (claim 13, Fig 16); WO 9207574 (Fig 1); US 5,644,033; Ha, et al., J. Immunol., 1992, 148(5):1526-1531; Mueller, et al., Eur. J. Biochem., 1992, 22:1621-1625; Hashimoto, et al., Immunogenetics, 1994, 40(4):287-295; Preud’homme, et al., Clin. Exp. Immunol., 1992, 90(1):141-146; Yu, et al., J. Immunol., 1992, 148(2) 633-637; Sakaguchi, et al., EMBO J., 1988, 7(11):3457-3464. (29) CXCR5 (Burkitt's lymphoma receptor 1, a G protein-coupled receptor that is activated by the CXCL13 chemokine, functions in lymphocyte migration and humoral defense, plays a role in HIV-2 infection and perhaps development of AIDS, lymphoma, myeloma, and leukemia); 372 aa, pI: 8.54 MW: 41959 TM: 7 [P] Gene Chromosome: 11q23.3, GenBank accession No. NP_001707.1) WO 2004 / 040000; WO 2004 / 015426; US 2003 / 105292 (Example 2); US 6,555,339 (Example 2); WO 2002 / 61087 (Fig 1); WO 2001 / 57188 (Claim 20, page 269); WO 2001 / 72830 (pages 12-13); WO 2000 / 22129 (Example 1, pages 152-153, Example 2, pages 254-256); WO 1999 / 28468 (claim 1, page 38); US 5,440,021 (Example 2, col 49-52); WO 9428931 (pages 56-58); WO 1992 / 17497 (claim 7, Fig 5); Dobner, et al., Eur. J. Immunol., 1992, 22:2795-2799; Barella, et al., Biochem. J., 1995, 309:773-779. (30) HLA-DOB (Beta subunit of MHC class II molecule (Ia antigen) that binds peptides and presents them to CD4+ T lymphocytes); 273 aa, pI: 6.56 MW: 30820 TM: 1 [P] Gene Chromosome: 6p21.3, GenBank accession No. NP_002111.1); Tonnelle, et al., EMBO J., 1985, 4(11):2839-2847; Jonsson, et al., Immunogenetics, 1989, 29(6):411-413; Beck, et al., J. Mol. Biol., 1992, 228:433-441; Strausberg, et al., Proc. Natl. Acad. Sci USA, 2002, 99:16899-16903; Servenius, et al., J. Biol. Chem., 1987, 262:8759-8766; Beck, et al., J. Mol. Biol., 1996, 255:1-13; Naruse, et al., Tissue Antigens, 2002, 59:512-519; WO 9958658 (claim 13, Fig 15); US 6,153,408 (Col 35-38); US 5,976,551 (col 168-170); US 6,011,146 (col 145-146); Kasahara, et al., Immunogenetics, 1989, 30(1):66-68; Larhammar, et al., J. Biol. Chem., 1985, 260(26):14111-14119. (31) P2X5 (Purinergic receptor P2X ligand-gated ion channel 5, an ion channel gated by extracellular ATP, may be involved in synaptic transmission and neurogenesis, deficiency may contribute to the pathophysiology of idiopathic detrusor instability); 422 aa), pI: 7.63, MW: 47206 TM: 1 [P] Gene Chromosome: 17p13.3, GenBank accession No. NP_002552.2); Le, et al., FEBS Lett., 1997, 418(1-2):195-199; WO 2004 / 047749; WO 2003 / 072035 (claim 10); Touchman, et al., Genome Res., 2000, 10:165- 173; WO 2002 / 22660 (claim 20); WO 2003 / 093444 (claim 1); WO 2003 / 087768 (claim 1); WO 2003 / 029277 (page 82). (32) CD72 (B-cell differentiation antigen CD72, Lyb-2), pI: 8.66, MW: 40225 TM: 1 [P] Gene Chromosome: 9p13.3, GenBank accession No. NP_001773.1) WO2004042346 (claim 65); WO 2003 / 026493 (pages 51-52, 57-58); WO 2000 / 75655 (pages 105-106); Von Hoegen, et al., J. Immunol., 1990, 144(12):4870-4877; Strausberg, et al., Proc. Natl. Acad. Sci USA, 2002, 99:16899-16903. (33) LY64 (Lymphocyte antigen 64 (RP105), type I membrane protein of the leucine rich repeat (LRR) family, regulates B-cell activation and apoptosis, loss of function is associated with increased disease activity in patients with systemic lupus erythematosis); 661 aa, pI: 6.20, MW: 74147 TM: 1 [P] Gene Chromosome: 5q12, GenBank accession No. NP_005573.1) US 2002 / 193567; WO 9707198 (claim 11, pages 39-42); Miura, et al., Genomics, 1996, 38(3):299-304; Miura, et al., Blood, 1998, 92:2815-2822; WO 2003 / 083047; WO 9744452 (claim 8, pages 57-61); WO 2000 / 12130 (pages 24-26). (34) FcRH1 (Fc receptor-like protein 1, a putative receptor for the immunoglobulin Fc domain that contains C2 type Ig-like and ITAM domains, may have a role in B-lymphocyte differentiation); 429 aa, pI: 5.28, MW: 46925 TM: 1 [P] Gene Chromosome: 1q21-1q22, GenBank accession No. NP_443170.1) WO 2003 / 077836; WO 2001 / 38490 (claim 6, Fig 18E-1-18-E-2); Davis, et al., Proc. Natl. Acad. Sci USA, 2001, 98(17):9772-9777; WO 2003 / 089624 (claim 8); EP 1347046 (claim 1); WO 2003 / 089624 (claim 7). (35) IRTA2 (Immunoglobulin superfamily receptor translocation associated 2, a putative immunoreceptor with possible roles in B cell development and lymphomagenesis; deregulation of the gene by translocation occurs in some B cell malignancies); 977 aa, pI: 6.88 MW: 106468 TM: 1 [P] Gene Chromosome: 1q21, GenBank accession No. Human:AF343662, AF343663, AF343664, AF343665, AF369794, AF397453, AK090423, AK090475, AL834187, AY358085; Mouse:AK089756, AY158090, AY506558; NP_112571.1. WO 2003 / 024392 (claim 2, Fig 97); Nakayama, et al., Biochem. Biophys. Res. Commun., 2000, 277(1):124-127; WO 2003 / 077836; WO 2001 / 38490 (claim 3, Fig 18B-1-18B-2). (36) TENB2 (TMEFF2, tomoregulin, TPEF, HPP1, TR, putative transmembrane proteoglycan, related to the EGF / heregulin family of growth factors and follistatin); 374 aa, NCBI Accession: AAD55776, AAF91397, AAG49451, NCBI RefSeq: NP_057276; NCBI Gene: 23671; OMIM: 605734; SwissProt Q9UIK5; GenBank accession No. AF179274; AY358907, CAF85723, CQ782436 WO 2004 / 074320; JP 2004113151; WO 2003 / 042661; WO 2003 / 009814; EP 1295944 (pages 69-70); WO 2002 / 30268 (page 329); WO 2001 / 90304; US 2004 / 249130; US 2004 / 022727; WO 2004 / 063355; US 2004 / 197325; US 2003 / 232350; US 2004 / 005563; US 2003 / 124579; Horie, et al., Genomics, 2000, 67:146- 152; Uchida, et al., Biochem. Biophys. Res. Commun., 1999, 266:593-602; Liang, et al., Cancer Res., 2000, 60:4907-12; Glynne-Jones, et al., Int. J. Cancer, 2001, 94(2):178-84. (37) PMEL17 (silver homolog; SILV; D12S53E; PMEL17; SI; SIL); ME20; gp100) BC001414; BT007202; M32295; M77348; NM_006928; McGlinchey, R.P., et al., Proc. Natl. Acad. Sci. U.S.A., 2009, 106(33):13731-13736; Kummer, M.P., et al., J. Biol. Chem., 2009, 284 (4):2296-2306. (38) TMEFF1 (transmembrane protein with EGF-like and two follistatin-like domains 1; Tomoregulin-1); H7365; C9orf2; C9ORF2; U19878; X83961; NM_080655; NM_003692; Harms, P.W., Genes Dev., 2003, 17(21):2624-2629; Gery, S., et al., Oncogene, 2003, 22(18):2723-2727. (39) GDNF-Ra1 (GDNF family receptor alpha 1; GFRA1; GDNFR; GDNFRA; RETL1; TRNR1; RET1L; GDNFR-alpha1; GFR-ALPHA-1); U95847; BC014962; NM_145793 NM_005264; Kim, M.H., et al., Mol. Cell. Biol., 2009, 29(8):2264- 2277; Treanor, J.J., et al., Nature, 1996, 382(6586):80-83. (40) Ly6E (lymphocyte antigen 6 complex, locus E; Ly67,RIG-E,SCA-2,TSA- 1); NP_002337.1; NM_002346.2; de Nooij-van Dalen, A.G., et al., Int. J. Cancer, 2003, 103(6): 768-774; Zammit, D.J., et al., Mol. Cell. Biol., 2002, 22(3):946-952. (41) TMEM46 (shisa homolog 2 (Xenopus laevis); SHISA2); NP_001007539.1; NM_001007538.1; Furushima, K., et al., Dev. Biol., 2007, 306(2):480- 492; Clark, H.F., et al., Genome Res., 2003, 13(10):2265-2270. (42) Ly6G6D (lymphocyte antigen 6 complex, locus G6D; Ly6-D, MEGT1); NP_067079.2; NM_021246.2; Mallya, M., et al., Genomics, 2002, 80(1):113-123; Ribas, G., et al., J. Immunol., 1999, 163(1):278-287. (43) LGR5 (leucine-rich repeat-containing G protein-coupled receptor 5; GPR49, GPR67); NP_003658.1; NM_003667.2; Salanti, G., et al., Am. J. Epidemiol., 2009, 170(5):537-545; Yamamoto, Y., et al., Hepatology, 2003, 37(3):528-533. (44) RET (ret proto-oncogene; MEN2A; HSCR1; MEN2B; MTC1; PTC; CDHF12; Hs.168114; RET51; RET-ELE1); NP_066124.1; NM_020975.4; Tsukamoto, H., et al., Cancer Sci., 2009100(10):1895-1901; Narita, N., et al., Oncogene, 2009, 28(34):3058- 3068. (45) LY6K (lymphocyte antigen 6 complex, locus K; LY6K; HSJ001348; FLJ35226); NP_059997.3; NM_017527.3; Ishikawa, N. et al., Cancer Res., 2007, 67(24):11601-11611; de Nooij-van Dalen, A.G., et al., Int. J. Cancer, 2003, 103(6):768-774. (46) GPR19 (G protein-coupled receptor 19; Mm.4787); NP_006134.1; NM_006143.2; Montpetit, A. and Sinnett, D., Hum. Genet., 1999, 105(1-2):162-164; O'Dowd, B.F., et al., FEBS Lett., 1996, 394(3):325-329. (47) GPR54 (KISS1 receptor; KISS1R; GPR54; HOT7T175; AXOR12); NP_115940.2; NM_032551.4; Navenot, J.M., et al., Mol. Pharmacol., 2009, 75(6):1300- 1306; Hata, K., et al., Anticancer Res.2009, 29(2):617-623. (48) ASPHD1 (aspartate beta-hydroxylase domain containing 1; LOC253982); NP_859069.2; NM_181718.3; Gerhard, D.S., et al., Genome Res., 2004, 14(10B):2121-2127. (49) Tyrosinase (TYR; OCAIA; OCA1A; tyrosinase; SHEP3); NP_000363.1; NM_000372.4; Bishop, D.T., et al., Nat. Genet., 2009, 41(8):920-925; Nan, H., et al., Int. J. Cancer, 2009, 125(4):909-917. (50) TMEM118 (ring finger protein, transmembrane 2; RNFT2; FLJ14627); NP_001103373.1; NM_001109903.1; Clark, H.F., et al., Genome Res., 2003, 13(10):2265- 2270; Scherer, S.E., et al., Nature, 2006, 440(7082):346-351. (51) GPR172A (G protein-coupled receptor 172A; GPCR41; FLJ11856; D15Ertd747e); NP_078807.1; NM_024531.3; Ericsson, T.A., et al., Proc. Natl. Acad. Sci. U.S.A., 2003, 100(11):6759-6764; Takeda, S., et al., FEBS Lett., 2002, 520(1-3):97-101. (52) CD33, a member of the sialic acid binding, immunoglobulin-like lectin family, is a 67-kDa glycosylated transmembrane protein. CD33 is expressed on most myeloid and monocytic leukemia cells in addition to committed myelomonocytic and erythroid progenitor cells. It is not seen on the earliest pluripotent stem cells, mature granulocytes, lymphoid cells, or nonhematopoietic cells (Sabbath, et al., J. Clin. Invest., 1985, 75:756-56; Andrews, et al., Blood, 1986, 68:1030-5). CD33 contains two tyrosine residues on its cytoplasmic tail, each of which is followed by hydrophobic residues similar to the immunoreceptor tyrosine-based inhibitory motif (ITIM) seen in many inhibitory receptors. (53) CLL-1 (CLEC12A, MICL, and DCAL2), encodes a member of the C- type lectin / C-type lectin-like domain (CTL / CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. The protein encoded by this gene is a negative regulator of granulocyte and monocyte function. Several alternatively spliced transcript variants of this gene have been described, but the full- length nature of some of these variants has not been determined. This gene is closely linked to other CTL / CTLD superfamily members in the natural killer gene complex region on chromosome 12p13 (Drickamer, K., Curr. Opin. Struct. Biol., 1999, 9(5):585–90; van Rhenen, A., et al., Blood, 2007, 110(7):2659–66; Chen, C.H., et al., Blood, 2006, 107(4):1459–67; Marshall, A.S., et al., Eur. J. Immunol., 2006, 36(8):2159–69; Bakker, A.B., et al., Cancer Res., 2005, 64(22):8443–50; Marshall, A.S., et al., J. Biol. Chem., 2004, 279 (15):14792–802). CLL-1 has been shown to be a type II transmembrane receptor comprising a single C-type lectin-like domain (which is not predicted to bind either calcium or sugar), a stalk region, a transmembrane domain and a short cytoplasmic tail containing an ITIM motif. (54) CD70 (CD27 ligand; CD27-L); cytokine that binds to CD27) plays a role in T-cell activation and induces the proliferation of co-stimulated T-cells and enhances the generation of cytolytic T-cells. CD70 protein is expressed on highly activated lymphocytes such as T- and B-cell lymphomas (Israel, B.F., et al., Mol. Cancer Ther., 2005, 4(12):2037– 44; O'Neill, R.E., et al., J. Immunol., 2017, 199(10):3700-3710; Leigh, N. D., et al., J. Immunol., 2017, 199(1):336-347; Itani, H. A., et al., Circ. Res., 2016, 118(8):1233-43; Burchill, M.A., et al., Eur. J. Immunol., 2015, 45(11):3140-9; Allam, A., et al., J. Immunol., 2014, 193(2):871-8). (55) CLDN18.2 (Claudin-18 Splice Variant 2); CLDN18 encodes the human gene, Claudin 18. It may also be known as: Claudin-18; SFTA5; and SFTPJ. The encoded protein has an amino acid length of 261 and a mass of 27.9 kDa. CLDN18 is a member of the Claudin family (WO 2013 / 167295; WO 2016 / 166122). The tight junction molecule claudin 18 isotype 2 (CLDN 18.2) is a cancer-associated splice variant of Claudin 18. CLDN 18.2 is a 27.8 kDa transmembrane protein comprising four membrane spanning domains with two small extracellular loops (loop1 embraced by hydrophobic region 1 and hydrophobic region 2; loop2 embraced by hydrophobic regions 3 and 4). CLDN 18.2 is a highly selective gastric lineage antigen, exclusively expressed on short-lived differentiated gastric epithelial cells and not detectable in any other normal human tissue. The antigen is ectopically expressed at significant levels in a diversity of human cancers including gastroesophageal and pancreatic cancer (Sahin, U., et al., Clin. Cancer Res., 2008, 14(23):7624-34). The CLDN18.2 protein is also frequently detected in lymph node metastases of gastric cancer and in distant metastases. CLDN 18.2 seems to be involved in proliferation of CLDN 18.2 positive tumor cells, since down regulation of the target by siRNA technology results in inhibition of proliferation of gastric cancer cells. 1MAB362 is a chimeric monoclonal antibody of IgGl subtype directed against CLDN 18.2. 1MAB362 recognizes the first extracellular domain of CLDN 18.2 with high affinity and specificity and does not bind to any other claudin family member including the closely related splice variant 1 of Claudin 18. (56) CD151 (Cluster of differentiation 151, Tspan24, PETA-3, SFA-1); human gene from the Raph blood group. The protein encoded by CD151 gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins and other transmembrane 4 superfamily proteins. It is involved in cellular processes including cell adhesion and may regulate integrin trafficking and / or function. This protein enhances cell motility, invasion and metastasis of cancer cells. Multiple alternatively spliced transcript variants that encode the same protein have been described for this gene (Berditchevski F., J. Cell Sci., 2002, 114(Pt 23):4143–51; Ashman, L.K., J. Biol. Regul. Homeost. Agents, 2003, 16(3):223–6; Sincock, P.M., et al., J. Histochem. Cytochem., 1997, 45(4):515–25; Fitter S, et al., Biochim. Biophys. Acta., 1998, 1398(1):75–85; Sincock, P.M., et al., J. Cell Sci., 1999, 112(Pt 6):833–44; Sterk, L.M., et al., J. Cell Biol., 2000, 149(4):969–82; Zhang, X.A., Mol. Biol. Cell., 2002, 13(1):1– 11). (57) ITGaV (integrin alpha-V, CD51; MSK8; VNRA; VTNR); a protein in humans is encoded by the ITGAV gene (Sosnoski, D. M., et al., J. Clin. Invest., 1988, 81(6):1993–8). ITGAV encodes integrin alpha chain V. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. Alpha V undergoes post- translational cleavage to yield disulfide-linked heavy and light chains that combine with multiple integrin beta chains to form different integrins. Among the known associating beta chains (beta chains 1,3,5,6, and 8; 'ITGB1', 'ITGB3', 'ITGB5', 'ITGB6', and 'ITGB8'), each can interact with extracellular matrix ligands; the alpha V beta 3 integrin, perhaps the most studied of these, is referred to as the Vitronectin receptor (VNR). In addition to adhesion, many integrins are known to facilitate signal transduction. Overexpression of the ITGAV gene is associated with progression and spread of colorectal cancer (Waisberg, J., et al., Anticancer Res., 2014, 34(10):5599–607) and prostate cancer (Cooper, C. R., et al., Neoplasia, 2002, 4(3):191–4). Monoclonal antibodies intetumumab and abituzumab target this protein which is found on some tumor cells (Élez, E., et al., Ann. Oncology, 2015, 26(1):132–40). Further exemplary antigens include, but are not limited to: (58) Nectin-4; (59) FGFR2; (60) FGFR3; (61) gpNMB; (62) GUCY2C; (63) CLDN6; (64) cMET; (65) CEACAM4; (66) CEACAM5; (67) CD29; (68) CD37; (69) CD352; (70) CD248; (71) MUC1; (72) CD123; (73) BCMA; (74) ADAM9; (75) 5T4; (76) P-cadherin; (77) CA9; (78) CD138; (79) CD166; (80) CD71; (81) CD22; (82) CD20; (83) CD74; (84) DLL3; (85) Folate Receptor alpha; (86) ITGa2; (87) ITGa3; (88) LAMP1; (89) LIV-1; (90) MMP14; (91) LRCC15; (92) MSLN; (93) PMSA; (94) PRLR; (95) PTK7; (96) SLAMF7; (97) SCL44A4; (98) SLTRK5; (99) TM4SF1; and (100) TROP2. In certain embodiments of the present invention, TAA are selected from the group consisting of TROP2, HER2, CD33, CD70, MUC1 / CanAg, MUC16, CD151 and ITGaV. EXEMPLARY ANTIBODIES (e.g., anti-Trop2 antibodies) Certain embodiments of the invention provide an antibody or fragment thereof (e.g., antigen binding domain). In certain embodiments, the antibody or fragment thereof is not conjugated to a payload drug. In certain embodiments, the antibody or fragment thereof is conjugated to a payload drug. For example, the antibody drug conjugate of the invention comprises an antibody or fragment thereof. Included in the scope of the embodiments of the invention are functional variants of the antibody or antigen binding domain described herein. The term “functional variant” as used herein refers to an antibody having an antigen binding domain with substantial or significant sequence identity or similarity to a parent antibody or antigen binding domain, which functional variant retains the biological activity of the antibody or antigen binding domain of which it is a variant. Functional variants encompass, for example, those variants of the antibody or antigen binding domain described herein (the parent antibody or antigen binding domain) that retain the ability to recognize target cells expressing a TAA, such as Trop2, to a similar extent, the same extent, or to a higher extent, as the parent antibody or antigen binding domain. In reference to the antibody or antigen binding domain, the functional variant can, for instance, be at least about 30%, about 50%, about 75%, about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more identical in amino acid sequence to the antibody or antigen binding domain. In certain embodiments, the antibody or antigen binding domain or functional variant thereof can be at least about 75% (e.g., 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%) or more identical in amino acid sequence to the antibody or antigen binding domain described herein. A functional variant can, for example, comprise the amino acid sequence of the parent antibody or antigen binding domain with at least one conservative amino acid substitution. Alternatively, or additionally, the functional variants can comprise the amino acid sequence of the parent antibody or antigen binding domain with at least one non-conservative amino acid substitution. In this case, it is preferable for the non-conservative amino acid substitution to not interfere with or inhibit the biological activity of the functional variant. The non-conservative amino acid substitution may enhance the biological activity of the functional variant, such that the biological activity of the functional variant is increased as compared to the parent antibody or antigen binding domain. The antibodies, including the antibody drug conjugate of the invention, include Fc engineered variants. In some embodiments, the mutations in the Fc region that result in modulated binding to one or more Fc receptors can include one or more of the following mutations: SD (S239D), SDIE (S239D / I332E), SE (S267E), SELF (S267E / L328F), SDIE (S239D / I332E), SDIEAL (S239D / I332E / A330L), GA (G236A), ALIE (A330L / I332E), GASDALIE (G236A / S239D / A330L / I332E), V9 (G237D / P238D / P271G / A330R), and V11 (G237D / P238D / H268D / P271G / A330R), and / or one or more mutations at the following amino acids: E345R, E233, G237, P238, H268, P271, L328 and A330. Additional Fc region modifications for modulating Fc receptor binding are described in, for example, U.S. Patent Application Publication 2016 / 0145350 and U.S. Patents 7,416,726 and 5,624,821, which are hereby incorporated by reference in their entireties herein. The antibodies, including the antibody drug conjugate of the invention, include glycan variants, such as afucosylation. In some embodiments, the Fc region of the binding agents are modified to have an altered glycosylation pattern of the Fc region compared to the native non-modified Fc region. Amino acid substitutions of the inventive antibody or antigen binding domains can be conservative amino acid substitutions. Conservative amino acid substitutions are known in the art, and include amino acid substitutions in which one amino acid having certain physical and / or chemical properties is exchanged for another amino acid that has the same or similar chemical or physical properties. For instance, the conservative amino acid substitution can be an acidic / negatively charged polar amino acid substituted for another acidic / negatively charged polar amino acid (e.g., Asp or Glu), an amino acid with a nonpolar side chain substituted for another amino acid with a nonpolar side chain (e.g., Ala, Gly, Val, Ile, Leu, Met, Phe, Pro, Trp, Cys, Val, etc.), a basic / positively charged polar amino acid substituted for another basic / positively charged polar amino acid (e.g., Lys, His, Arg, etc.), an uncharged amino acid with a polar side chain substituted for another uncharged amino acid with a polar side chain (e.g., Asn, Gln, Ser, Thr, Tyr, etc.), an amino acid with a beta-branched side-chain substituted for another amino acid with a beta-branched side-chain (e.g., Ile, Thr, and Val), an amino acid with an aromatic side-chain substituted for another amino acid with an aromatic side chain (e.g., His, Phe, Trp, and Tyr), etc. The antibody or antigen binding domain can consist essentially of the specified amino acid sequence or sequences described herein, such that other components, e.g., other amino acids, do not materially change the biological activity of the antibody or antigen binding domain functional variant. Methods for generating antibodies are described in, for example, Köhler and Milstein, Eur. J. Immunol., 5: 511-519 (1976); Harlow and Lane (eds.), Antibodies: A Laboratory Manual, CSH Press (1988); and Janeway et al. (eds.), Immunobiology, 9th Ed., Garland Publishing, New York, NY (2017). In certain embodiments, a human or chimeric antibody or antibody fragment can be generated using a transgenic animal (e.g., a mouse) wherein one or more endogenous immunoglobulin genes are replaced with one or more human immunoglobulin genes. Examples of transgenic mice wherein endogenous antibody genes are effectively replaced with human antibody genes include, but are not limited to, the Medarex HUMAB-MOUSE™, the Kirin TC MOUSE™, and the Kyowa Kirin KM- MOUSE™ (see, e.g., Lonberg, Nat. Biotechnol., 23(9): 1117-25 (2005), and Lonberg, Handb. Exp. Pharmacol., 181: 69-97 (2008)). A humanized antibody can be generated using any suitable method known in the art (see, e.g., An, Z. (ed.), Therapeutic Monoclonal Antibodies: From Bench to Clinic, John Wiley & Sons, Inc., Hoboken, New Jersey (2009)), including, e.g., grafting of non-human CDRs onto a human antibody scaffold (see, e.g., Kashmiri et al., Methods, 36(1): 25-34 (2005); and Hou et al., J. Biochem., 144(1): 115-120 (2008) and use of phage display (see, e.g., Fellouse, et al., Journal of Molecular Biology, 373(4): 924-940 (2007) and Glanville, et al., PNAS, 106(48): 20216-20221 (2009)). In an exemplary embodiment, the antibody or ADC of the invention comprise an antibody that comprises an antigen binding domain that specifically recognizes and binds human and non-human primate Trop2 (also known as Tumor associated calcium signal transducer 2, also see NCBI accession numbers NP_002344 and XP_005543292). In some embodiments, the Trop2 binding agent (e.g., antibody or fragment thereof) binds to human Trop2, for example, a protein comprising SEQ ID NO: 38. However, binding agents that bind to any Trop2 homolog or paralog also are encompassed. In some embodiments, the Trop2 protein comprises at least about 70%, about 75%, about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more sequence identity to SEQ ID NO: 38. In some embodiments, the binding agent binds human Trop2 and cynomolgus Trop2; or human, cynomolgus, and mouse Trop2. MARGPGLAPPPLRLPLLLLVLAAVTGHTAAQDNCTCPTNKMTVCSPDGPGGRCQCRALGSGMAVDCSTLT SKCLLLKARMSAPKNARTLVRPSEHALVDNDGLYDPDCDPEGRFKARQCNQTSVCWCVNSVGVRRTDKGD LSLRCDELVRTHHILIDLRHRPTAGAFNHSDLDAELRRLFRERYRLHPKFVAAVHYEQPTIQIELRQNTS QKAAGDVDIGDAAYYFERDIKGESLFQGRGGLDLRVRGEPLQVERTLIYYLDEIPPKFSMKRLTAGLIAV IVVVVVALVAGMAVLVITNRRKSGKYKKVEIKELGELRKEPSL SEQ ID NO: 38 A method is provided for delivering a payload to a cell expressing Trop2 comprising administering to the cell, or mammal comprising the cell, an ADC comprising an anti-Trop2 antibody covalently attached to a payload (e.g., via a linker or without a linker). The invention also provides a Trop2 binding agent (e.g., antibody or fragment thereof) comprising an immunoglobulin heavy chain variable region polypeptide and an immunoglobulin light chain variable region polypeptide. The Trop2 binding agent specifically binds Trop2. The binding specificity of the agent allows for targeting Trop2 expressing cells, for instance, to deliver therapeutic payloads to such cells. In some embodiments, the Trop2 binding agent binds Trop2 without substantially inhibiting or preventing Trop2 from binding to one or more of its ligand(s) (e.g., claudin 1, claudin 7, or IGF-1). However, in other embodiments, the Trop2 binding agent can completely or partially block (inhibit or prevent) binding of Trop2 to one or more of its binding partners such as the fibronectin receptor a5b1 (integrin α5β1), such that the antibody can be used to inhibit Trop2 mediated cancer cell migration or metastasis (Trerotola M. et al., Cancer Research, 2013, May 15;73(10):3155-67), or may completely or partially block cis- or trans-dimerization of the Trop2 receptor’s ectodomains (Sun M. et al., iScience, 2021, Oct 22; 24(10): 103190). The antibody or antigen-binding antibody fragment can be monospecific for Trop2, or can be bispecific or multi-specific. For instance, in bivalent or multivalent antibodies or antibody fragments, the binding domains can be different, targeting different epitopes of the same antigen, or targeting different antigens. Methods of constructing multivalent binding constructs are known in the art. Bispecific and multispecific antibodies are known in the art. Furthermore, a diabody, triabody, or tetrabody can be provided, which is a dimer, trimer, or tetramer of polypeptide chains each comprising a VHconnected to a VLby a peptide linker that is too short to allow pairing between the VHand VLon the same polypeptide chain, thereby driving the pairing between the complementary domains on different VH -VL polypeptide chains to generate a multimeric molecule having two, three, or four functional antigen binding sites. Also, bis-scFv fragments, which are small scFv fragments with two different variable domains can be generated to produce bispecific bis-scFv fragments capable of binding two different epitopes. Fab dimers (Fab2) and Fab trimers (Fab3) can be produced using genetic engineering methods to create multispecific constructs based on Fab fragments. The Trop2-binding agent also can be an antibody conjugate. In this respect, the Trop2-binding agent can be a conjugate of (1) an antibody, an alternative scaffold, or fragments thereof, and (2) a protein or non-protein moiety. For example, the Trop2 binding agent can be conjugated to a peptide, a fluorescent molecule, chemotherapeutic, a radioisotope, or other cytotoxic payload agent. The Trop2-binding agent can be, or can be obtained from, a human antibody, a non- human antibody, a humanized antibody, or a chimeric antibody, or corresponding antibody fragments. A “chimeric” antibody is an antibody or fragment thereof typically comprising human constant regions and non-human variable regions. A “humanized” antibody is a monoclonal antibody typically comprising a human antibody scaffold with non-human origin amino acids or sequences in at least one CDR (e.g., 1, 2, 3, 4, 5, or all six CDRs). Furthermore, in some embodiments, the Trop2-binding agent provided herein may cause cellular internalization of Trop2 or the binding agent complex upon binding to Trop2 on the cell surface. Without wishing to be bound by any particular theory or mechanism of action, it is believed that certain Trop2-binding agents according to this embodiment may cause Trop2 internalization upon binding, and remain bound to Trop2 during internalization resulting in internalization of the binding agent along with Trop2. Cellular internalization of Trop2 and bound Trop2 binding agent can be determined by any suitable method, such as a method described herein, or assaying for persistence on the cell surface and / or detection of internalized antibodies. In some embodiments, the Trop2 binding agent internalizes strongly enough that at least about 25% (e.g., at least about 35%, at least about 50%, at least about 75%, or at least about 90%) of the Trop2 binding agent that binds Trop2 on the cell surface is internalized (e.g., using a surface persistence assay, about 75% or less, about 65% or less, about 50% or less, about 25% or less or about 10% or less of Trop2 binding agent molecules bound to Trop2 on the cell surface at the beginning of the assay remain bound at the end of the assay). In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises one or more (e.g., 1, 2, 3, 4, 5, or 6) complementarity determining region (CDRs) as described herein (e.g., as described in Tables S1-S6). In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide as described herein, and / or an immunoglobulin light chain variable region polypeptide as described herein. In certain embodiments, the immunoglobulin heavy chain variable region polypeptide of the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises a complementarity determining region 1 (HCDR1) comprising an amino acid sequence that is at least 75% (e.g., 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to NYGMN (SEQ ID NO: 14), a complementarity determining region 2 (HCDR2) comprising an amino acid sequence that is at least 75% (e.g., 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to WINTKTGEPTYAEEFKG (SEQ ID NO: 16) or WINTKTGEPTYAQEFTG (SEQ ID NO: 21), and a complementarity determining region 3 (HCDR3) comprising an amino acid sequence that is at least 75% (e.g., 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to GGYGSSYWYFDV (SEQ ID NO: 18). In certain embodiments, the immunoglobulin light chain variable region polypeptide of the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises a complementarity determining region 1 (LCDR1) comprising an amino acid sequence that is at least 75% (e.g., 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to KASQDVSIAVA (SEQ ID NO: 27), a complementarity determining region 2 (LCDR2) comprising an amino acid sequence that is at least 75% (e.g., 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to SASYRYT (SEQ ID NO: 29), and a complementarity determining region 3 (LCDR3) comprising an amino acid sequence that is at least 75% (e.g., 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to QQHYITPLT (SEQ ID NO: 31). In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising a complementarity determining region 1 (HCDR1) comprising an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to NYGMN (SEQ ID NO: 14), a complementarity determining region 2 (HCDR2) comprising an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to WINTKTGEPTYAEEFKG (SEQ ID NO: 16) or WINTKTGEPTYAQEFTG (SEQ ID NO: 21), and a complementarity determining region 3 (HCDR3) comprising an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to GGYGSSYWYFDV (SEQ ID NO: 18); and / or an immunoglobulin light chain variable region polypeptide comprising a complementarity determining region 1 (LCDR1) comprising an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to KASQDVSIAVA (SEQ ID NO: 27), a complementarity determining region 2 (LCDR2) comprising an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to SASYRYT (SEQ ID NO: 29), and a complementarity determining region 3 (LCDR3) comprising an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to QQHYITPLT (SEQ ID NO: 31). In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising a complementarity determining region 1 (HCDR1) comprising an amino acid sequence that is at least 90% identical to NYGMN (SEQ ID NO: 14), a complementarity determining region 2 (HCDR2) comprising an amino acid sequence that is at least 90% identical to WINTKTGEPTYAQEFTG (SEQ ID NO: 21), and a complementarity determining region 3 (HCDR3) comprising an amino acid sequence that is at least 90% identical to GGYGSSYWYFDV (SEQ ID NO: 18); and / or an immunoglobulin light chain variable region polypeptide comprising a complementarity determining region 1 (LCDR1) comprising an amino acid sequence that is at least 90% identical to KASQDVSIAVA (SEQ ID NO: 27), a complementarity determining region 2 (LCDR2) comprising an amino acid sequence that is at least 90% identical to SASYRYT (SEQ ID NO: 29), and a complementarity determining region 3 (LCDR3) comprising an amino acid sequence that is at least 90% identical to QQHYITPLT (SEQ ID NO: 31). In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising a complementarity determining region 1 (HCDR1) comprising NYGMN (SEQ ID NO: 14), a complementarity determining region 2 (HCDR2) comprising WINTKTGEPTYAEEFKG (SEQ ID NO: 16) or WINTKTGEPTYAQEFTG (SEQ ID NO: 21), and a complementarity determining region 3 (HCDR3) comprising GGYGSSYWYFDV (SEQ ID NO: 18); and / or an immunoglobulin light chain variable region polypeptide comprising a complementarity determining region 1 (LCDR1) comprising KASQDVSIAVA (SEQ ID NO: 27), a complementarity determining region 2 (LCDR2) comprising SASYRYT (SEQ ID NO: 29), and a complementarity determining region 3 (LCDR3) comprising QQHYITPLT (SEQ ID NO: 31). In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising a complementarity determining region 1 (HCDR1) comprising SEQ ID NO: 14, a complementarity determining region 2 (HCDR2) comprising SEQ ID NO: 16, and a complementarity determining region 3 (HCDR3) comprising SEQ ID NO: 18. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising a complementarity determining region 1 (HCDR1) comprising SEQ ID NO: 14, a complementarity determining region 2 (HCDR2) comprising SEQ ID NO: 21, and a complementarity determining region 3 (HCDR3) comprising SEQ ID NO: 18. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin light chain variable region polypeptide comprising a complementarity determining region 1 (LCDR1) comprising SEQ ID NO: 27, a complementarity determining region 2 (LCDR2) comprising SEQ ID NO: 29, and a complementarity determining region 3 (LCDR3) comprising SEQ ID NO: 31. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises one or more complementarity determining regions (CDRs) and / or Framework region (FRs) as described herein (e.g., as described in Tables S1-S6). In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises one or more (e.g., 1, 2, 3, 4, 5, 6, 7 or 8) Framework region (FRs) as described herein (e.g., as described in Tables S1-S6). In particular embodiments, the binding agent comprises an immunoglobulin heavy chain polypeptide and an immunoglobulin light chain polypeptide, wherein the immunoglobulin heavy chain polypeptide comprises a first framework region, a second framework region, a third framework region, and / or a fourth framework region; and / or the immunoglobulin light chain polypeptide comprises a first framework region, a second framework region, a third framework region, and / or a fourth framework region; and / or the immunoglobulin heavy chain polypeptide and light chain polypeptide comprises any combination of the framework regions listed in Tables S1-S6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 1-4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 5-6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 1-4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 5-6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 5-6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 1-4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NO: 2 or 4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 1-4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 5-6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO: 2 or 4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 5-6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO: 4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 5-6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO: 1, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO:5. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO: 1, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO:6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO: 2, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO:6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO: 3, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO:6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO: 4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO:6. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO: 2 or 4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO:5. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO: 2, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO:5. In certain embodiments, the Trop2-binding agent (e.g., antibody or fragment thereof such as the antigen binding domain) comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO: 4, and / or an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of SEQ ID NO:5. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises a human IgG1, IgG2, IgG3, or IgG4 Fc domain. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises a human IgG1 Fc domain. In certain embodiments, the Trop2- binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising a human IgG1, IgG2, IgG3, or IgG4 Fc region polypeptide. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising a human IgG1 Fc region polypeptide. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises a human kappa light chain polypeptide. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises a human lambda light chain polypeptide. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 7, 9, 10, 11, or 34-37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 8 or 12. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 7, 9, 10, 11, or 34-37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 8 or 12. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 7, 9, 10, 11, or 34-37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:8. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 7, 10, 35, or 37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:8. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7 or 37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:8 or 12. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 7, 9, 10, 11, or 34-37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 8 or 12. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 7 or 37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 8 or 12. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 7, 10, 35, or 37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 8 or 12. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of SEQ ID NO: 9 or 34, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence of SEQ ID NO:8. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of SEQ ID NO: 10 or 35, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence of SEQ ID NO:8. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of SEQ ID NO: 11 or 36, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence of SEQ ID NO:8. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of SEQ ID NO: 7 or 37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence of SEQ ID NO:8. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of any one of SEQ ID NO: 7, 10, 35, or 37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence of SEQ ID NO:12. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of SEQ ID NO: 10 or 35, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence of SEQ ID NO:12. In certain embodiments, the Trop2-binding agent (e.g., antibody) comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of SEQ ID NO: 7 or 37, and / or an immunoglobulin light chain polypeptide comprising an amino acid sequence of SEQ ID NO:12. In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises the Variable heavy chain (VH) of SEQ ID NO:1 QIQLVQSGHEVKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWINTK TGEPTYAEEFKGRFVFSLETSASTAYLQISSLKAEDMAMYFCGRGGYGSSYWYFDV WGQGTTVTVSS (SEQ ID NO:1). In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises one or more heavy chain CDR (complementarity determining region) or heavy chain framework (HFR) sequences of SEQ ID NO.13-19. Table S1. In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises the Variable heavy chain (VH) of SEQ ID NO:2 QVQLVQSGHEVKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWINTK TGEPTYAQEFTGRFVFSLDTSVSTAYLQISSLKAEDMAVYFCGRGGYGSSYWYFDV WGQGTTVTVSS (SEQ ID NO:2). In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises one or more heavy chain CDR (complementarity determining region) or heavy chain framework (HFR) sequences of SEQ ID NO.14, 15, 18, 19, 20, 21 or 22. Table S2. In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises the Variable heavy chain (VH) of SEQ ID NO:3 QVQLVQSGHELKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWINTK TGEPTYAQEFTGRFVFSLDTSVSTAYLQISSLKAEDMAVYYCGRGGYGSSYWYFDV WGQGTTVTVSS (SEQ ID NO:3). In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises one or more heavy chain CDR (complementarity determining region) or heavy chain framework (HFR) sequences of SEQ ID NO.14, 15, 18, 19, 21, 23 or 24. Table S3. In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises the Variable heavy chain (VH) of SEQ ID NO:4 QVQLVQSGHEVKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWINTK TGEPTYAQEFTGRFVFSLDTSVSTAYLQISSLKAEDTAVYFCGRGGYGSSYWYFDVW GQGTTVTVSS (SEQ ID NO:4). In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises one or more heavy chain CDR (complementarity determining region) or heavy chain framework (HFR) sequences of SEQ ID NO.14, 15, 18, 19, 20, 21 or 25. Table S4. In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises the Variable light chain (VL) of SEQ ID NO:5 DIQMTQSPSSLSASVGDRVTITCKASQDVSIAVAWYQQKPGKAPKVLIYSASYRYTG VPDRFSGSGSGTDFTFTISSLQPEDIAVYYCQQHYITPLTFGGGTKVEIKR (SEQ ID NO:5). In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises one or more light chain CDR (complementarity determining region) or light chain framework (LFR) sequences of SEQ ID NO.26-32. Table S5. In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises the Variable light chain (VL) of SEQ ID NO:6 DIQMTQSPSSLSASVGDRVTITCKASQDVSIAVAWYQQKPGKAPKVLIYSASYRYTG VPSRFSGSGSGTDFTFTISSLQPEDIAVYYCQQHYITPLTFGGGTKVEIKR (SEQ ID NO:6). In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises one or more light chain CDR (complementarity determining region) or light chain framework (LFR) sequences of SEQ ID NO.26-29 or 31-33. Table S6. In an embodiment of the invention, the LFR4 region comprises FGGGTKVEIK. In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises the Variable light chain (VL) of SEQ ID NO:39 DIQMTQSPSSLSASVGDRVTITCKASQDVSIAVAWYQQKPGKAPKVLIYSASYRYTG VPDRFSGSGSGTDFTFTISSLQPEDIAVYYCQQHYITPLTFGGGTKVEIK (SEQ ID NO:39). In an embodiment of the invention, the Trop2-targeting antibody or antigen binding domain comprises the Variable light chain (VL) of SEQ ID NO:40 DIQMTQSPSSLSASVGDRVTITCKASQDVSIAVAWYQQKPGKAPKVLIYSASYRYTG VPSRFSGSGSGTDFTFTISSLQPEDIAVYYCQQHYITPLTFGGGTKVEIK (SEQ ID NO:40). In an embodiment of the invention, the Trop2-targeting antibody comprises the heavy chain of SEQ ID NO:9 KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:11). In an embodiment of the invention, the Trop2-targeting antibody comprises the heavy chain of SEQ ID NO:7 TISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:35). In an embodiment of the invention, the Trop2-targeting antibody comprises the heavy chain of SEQ ID NO:36 In an embodiment of the invention, the Trop2-targeting antibody comprises the light chain of SEQ ID NO:8 NO:43). In an embodiment of ADC of the invention, the Trop2-targeting antibody comprises the CDR regions, FR regions, H and / or L variable regions, heavy chain, and / or light chain of DS1062a as described in International Patent application WO2020 / 240467, which is incorporated by reference herein. In an embodiment of ADC of the invention, the Trop2-targeting antibody (TINA) comprises Heavy chain sequence: S G (S Q NO: ), and Light Chain sequence: Antibody Fragments In certain embodiments, an antibody provided herein is an antibody fragment. Antibody fragments include, but are not limited to, Fab, Fab’, Fab’-SH, F(ab’)2, Fv, and scFv fragments, and other fragments described below. For a review of certain antibody fragments, see Hudson et al. Nat. Med.9:129-134 (2003). For a review of scFv fragments, see, e.g., Pluckthün, in The Pharmacology of Monoclonal Antibodies, vol.113, Rosenburg and Moore eds., (Springer-Verlag, New York), pp.269-315 (1994); see also WO 93 / 16185; and U.S. Patent Nos.5,571,894 and 5,587,458. For discussion of Fab and F(ab')2fragments comprising salvage receptor binding epitope residues and having increased in vivo half-life, see U.S. Patent No.5,869,046. Diabodies are antibody fragments with two antigen-binding sites that may be bivalent or bispecific. See, for example, EP 404,097; WO 1993 / 01161; Hudson et al., Nat. Med.9:129-134 (2003); and Hollinger et al., Proc. Natl. Acad. Sci. USA 90: 6444-6448 (1993). Triabodies and tetrabodies are also described in Hudson et al., Nat. Med.9:129-134 (2003). Single-domain antibodies are antibody fragments comprising all or a portion of the heavy chain variable domain or all or a portion of the light chain variable domain of an antibody. In certain embodiments, a single-domain antibody is a human single-domain antibody (Domantis, Inc., Waltham, MA; see, e.g., U.S. Patent No.6,248,516 B1). Antibody fragments can be made by various techniques, including but not limited to proteolytic digestion of an intact antibody as well as production by recombinant host cells (e.g. E. coli or phage), as described herein. Chimeric and Humanized Antibodies In certain embodiments, an antibody provided herein is a chimeric antibody. Certain chimeric antibodies are described, e.g., in U.S. Patent No.4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)). In one example, a chimeric antibody comprises a non-human variable region (e.g., a variable region derived from a mouse, rat, hamster, rabbit, or non-human primate, such as a monkey) and a human constant region. In a further example, a chimeric antibody is a “class switched” antibody in which the class or subclass has been changed from that of the parent antibody. Chimeric antibodies include antigen-binding fragments thereof. In certain embodiments, a chimeric antibody is a humanized antibody. Typically, a non- human antibody is humanized to reduce immunogenicity to humans, while retaining the specificity and affinity of the parental non-human antibody. Generally, a humanized antibody comprises one or more variable domains in which HVRs, e.g., CDRs, (or portions thereof) are derived from a non-human antibody, and FRs (or portions thereof) are derived from human antibody sequences. A humanized antibody optionally will also comprise at least a portion of a human constant region. In some embodiments, some FR residues in a humanized antibody are substituted with corresponding residues from a non-human antibody (e.g., the antibody from which the HVR residues are derived), e.g., to restore or improve antibody specificity or affinity. Humanized antibodies and methods of making them are reviewed, e.g., in Almagro and Fransson, Front. Biosci.13:1619-1633 (2008), and are further described, e.g., in Riechmann et al., Nature 332:323-329 (1988); Queen et al., Proc. Nat’l Acad. Sci. USA 86:10029-10033 (1989); US Patent Nos.5, 821,337, 7,527,791, 6,982,321, and 7,087,409; Kashmiri et al., Methods 36:25-34 (2005) (describing SDR (a-CDR) grafting); Padlan, Mol. Immunol.28:489-498 (1991) (describing “resurfacing”); Dall’Acqua et al., Methods 36:43-60 (2005) (describing “FR shuffling”); and Osbourn et al., Methods 36:61-68 (2005) and Klimka et al., Br. J. Cancer, 83:252-260 (2000) (describing the “guided selection” approach to FR shuffling). Human framework regions that may be used for humanization include but are not limited to: framework regions selected using the “best-fit” method (see, e.g., Sims et al. J. Immunol. 151:2296 (1993)); framework regions derived from the consensus sequence of human antibodies of a particular subgroup of light or heavy chain variable regions (see, e.g., Carter et al. Proc. Natl. Acad. Sci. USA, 89:4285 (1992); and Presta et al. J. Immunol., 151:2623 (1993)); human mature (somatically mutated) framework regions or human germline framework regions (see, e.g., Almagro and Fransson, Front. Biosci.13:1619-1633 (2008)); and framework regions derived from screening FR libraries (see, e.g., Baca et al., J. Biol. Chem.272:10678-10684 (1997) and Rosok et al., J. Biol. Chem.271:22611-22618 (1996)). Human Antibodies In certain embodiments, an antibody provided herein is a human antibody. Human antibodies can be produced using various techniques known in the art. Human antibodies are described generally in van Dijk and van de Winkel, Curr. Opin. Pharmacol.5: 368-74 (2001) and Lonberg, Curr. Opin. Immunol.20:450-459 (2008). Human antibodies may be prepared by administering an immunogen to a transgenic animal that has been modified to produce intact human antibodies or intact antibodies with human variable regions in response to antigenic challenge. Such animals typically contain all or a portion of the human immunoglobulin loci, which replace the endogenous immunoglobulin loci, or which are present extrachromosomally or integrated randomly into the animal’s chromosomes. In such transgenic mice, the endogenous immunoglobulin loci have generally been inactivated. For review of methods for obtaining human antibodies from transgenic animals, see Lonberg, Nat. Biotech.23:1117-1125 (2005). See also, e.g., U.S. Patent Nos.6,075,181 and 6,150,584 describing XENOMOUSETMtechnology; U.S. Patent No.5,770,429 describing HUMAB® technology; U.S. Patent No.7,041,870 describing K-M MOUSE® technology, and U.S. Patent Application Publication No. US 2007 / 0061900, describing VELOCIMOUSE® technology). Human variable regions from intact antibodies generated by such animals may be further modified, e.g., by combining with a different human constant region. Human antibodies can also be made by hybridoma-based methods. Human myeloma and mouse-human heteromyeloma cell lines for the production of human monoclonal antibodies have been described. (See, e.g., Kozbor J. Immunol., 133: 3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, pp.51-63 (Marcel Dekker, Inc., New York, 1987); and Boerner et al., J. Immunol., 147: 86 (1991).) Human antibodies generated via human B-cell hybridoma technology are also described in Li et al., Proc. Natl. Acad. Sci. USA, 103:3557-3562 (2006). Additional methods include those described, for example, in U.S. Patent No.7,189,826 (describing production of monoclonal human IgM antibodies from hybridoma cell lines) and Ni, Xiandai Mianyixue, 26(4):265-268 (2006) (describing human-human hybridomas). Human hybridoma technology (Trioma technology) is also described in Vollmers and Brandlein, Histology and Histopathology, 20(3):927-937 (2005) and Vollmers and Brandlein, Methods and Findings in Experimental and Clinical Pharmacology, 27(3):185-91 (2005). Human antibodies may also be generated by isolating Fv clone variable domain sequences selected from human-derived phage display libraries. Such variable domain sequences may then be combined with a desired human constant domain. Techniques for selecting human antibodies from antibody libraries are described below. Library-Derived Antibodies Antibodies of the invention may be isolated by screening combinatorial libraries for antibodies with the desired activity or activities. For example, a variety of methods are known in the art for generating phage display libraries and screening such libraries for antibodies possessing the desired binding characteristics. Such methods are reviewed, e.g., in Hoogenboom et al. in Methods in Molecular Biology 178:1-37 (O’Brien et al., ed., Human Press, Totowa, NJ, 2001) and further described, e.g., in the McCafferty et al., Nature 348:552-554; Clackson et al., Nature 352: 624-628 (1991); Marks et al., J. Mol. Biol.222: 581-597 (1992); Marks and Bradbury, in Methods in Molecular Biology 248:161-175 (Lo, ed., Human Press, Totowa, NJ, 2003); Sidhu et al., J. Mol. Biol.338(2): 299-310 (2004); Lee et al., J. Mol. Biol.340(5): 1073- 1093 (2004); Fellouse, Proc. Natl. Acad. Sci. USA 101(34): 12467-12472 (2004); and Lee et al., J. Immunol. Methods 284(1-2): 119-132(2004). In certain phage display methods, repertoires of VH and VL genes are separately cloned by polymerase chain reaction (PCR) and recombined randomly in phage libraries, which can then be screened for antigen-binding phage as described in Winter et al., Ann. Rev. Immunol., 12: 433- 455 (1994). Phage typically display antibody fragments, either as single-chain Fv (scFv) fragments or as Fab fragments. Libraries from immunized sources provide high-affinity antibodies to the immunogen without the requirement of constructing hybridomas. Alternatively, the naive repertoire can be cloned (e.g., from human) to provide a single source of antibodies to a wide range of non-self and also self antigens without any immunization as described by Griffiths et al., EMBO J, 12: 725-734 (1993). Finally, naive libraries can also be made synthetically by cloning unrearranged V-gene segments from stem cells, and using PCR primers containing random sequence to encode the highly variable CDR3 regions and to accomplish rearrangement in vitro, as described by Hoogenboom and Winter, J. Mol. Biol., 227: 381-388 (1992). Patent publications describing human antibody phage libraries include, for example: US Patent No. 5,750,373, and US Patent Publication Nos.2005 / 0079574, 2005 / 0119455, 2005 / 0266000, 2007 / 0117126, 2007 / 0160598, 2007 / 0237764, 2007 / 0292936, and 2009 / 0002360. Antibodies or antibody fragments isolated from human antibody libraries are considered human antibodies or human antibody fragments herein. Multispecific Antibodies In certain embodiments, an antibody provided herein is a multispecific antibody, e.g. a bispecific antibody. Multispecific antibodies are monoclonal antibodies that have binding specificities for at least two different sites. In certain embodiments, bispecific antibodies may bind to two different epitopes of the same target. Bispecific antibodies may also be used to localize cytotoxic agents to cells which express the target. Bispecific antibodies can be prepared as full length antibodies or antibody fragments. Techniques for making multispecific antibodies include, but are not limited to, recombinant co-expression of two immunoglobulin heavy chain-light chain pairs having different specificities (see Milstein and Cuello, Nature 305: 537 (1983)), WO 93 / 08829, and Traunecker et al., EMBO J.10: 3655 (1991)), and “knob-in-hole” engineering (see, e.g., U.S. Patent No. 5,731,168). The term “knob-into-hole” or “KnH” technology as used herein refers to the technology directing the pairing of two polypeptides together in vitro or in vivo by introducing a protuberance (knob) into one polypeptide and a cavity (hole) into the other polypeptide at an interface in which they interact. For example, KnHs have been introduced in the Fc:Fc binding interfaces, CL:CH1 interfaces or VH / VL interfaces of antibodies (see, e.g., US 2011 / 0287009, US2007 / 0178552, WO 96 / 027011, WO 98 / 050431, Zhu et al., 1997, Protein Science 6:781-788, and WO2012 / 106587). In some embodiments, KnHs drive the pairing of two different heavy chains together during the manufacture of multispecific antibodies. For example, multispecific antibodies having KnH in their Fc regions can further comprise single variable domains linked to each Fc region, or further comprise different heavy chain variable domains that pair with similar or different light chain variable domains. KnH technology can be also be used to pair two different receptor extracellular domains together or any other polypeptide sequences that comprises different target recognition sequences (e.g., including affibodies, peptibodies and other Fc fusions). The term “knob mutation” as used herein refers to a mutation that introduces a protuberance (knob) into a polypeptide at an interface in which the polypeptide interacts with another polypeptide. In some embodiments, the other polypeptide has a hole mutation. The term “hole mutation” as used herein refers to a mutation that introduces a cavity (hole) into a polypeptide at an interface in which the polypeptide interacts with another polypeptide. In some embodiments, the other polypeptide has a knob mutation. A brief nonlimiting discussion is provided below. A “protuberance” refers to at least one amino acid side chain which projects from the interface of a first polypeptide and is therefore positionable in a compensatory cavity in the adjacent interface (i.e. the interface of a second polypeptide) so as to stabilize the heteromultimer, and thereby favor heteromultimer formation over homomultimer formation, for example. The protuberance may exist in the original interface or may be introduced synthetically (e.g., by altering nucleic acid encoding the interface). In some embodiments, nucleic acid encoding the interface of the first polypeptide is altered to encode the protuberance. To achieve this, the nucleic acid encoding at least one “original” amino acid residue in the interface of the first polypeptide is replaced with nucleic acid encoding at least one “import” amino acid residue which has a larger side chain volume than the original amino acid residue. It will be appreciated that there can be more than one original and corresponding import residue. The side chain volumes of the various amino residues are shown, for example, in Table 1 of US2011 / 0287009. A mutation to introduce a “protuberance” may be referred to as a “knob mutation.” In some embodiments, import residues for the formation of a protuberance are naturally occurring amino acid residues selected from arginine (R), phenylalanine (F), tyrosine (Y) and tryptophan (W). In some embodiments, an import residue is tryptophan or tyrosine. In some embodiment, the original residue for the formation of the protuberance has a small side chain volume, such as alanine, asparagine, aspartic acid, glycine, serine, threonine or valine. A “cavity” refers to at least one amino acid side chain which is recessed from the interface of a second polypeptide and therefore accommodates a corresponding protuberance on the adjacent interface of a first polypeptide. The cavity may exist in the original interface or may be introduced synthetically (e.g. by altering nucleic acid encoding the interface). In some embodiments, nucleic acid encoding the interface of the second polypeptide is altered to encode the cavity. To achieve this, the nucleic acid encoding at least one “original” amino acid residue in the interface of the second polypeptide is replaced with DNA encoding at least one “import” amino acid residue which has a smaller side chain volume than the original amino acid residue. It will be appreciated that there can be more than one original and corresponding import residue. In some embodiments, import residues for the formation of a cavity are naturally occurring amino acid residues selected from alanine (A), serine (S), threonine (T) and valine (V). In some embodiments, an import residue is serine, alanine or threonine. In some embodiments, the original residue for the formation of the cavity has a large side chain volume, such as tyrosine, arginine, phenylalanine or tryptophan. A mutation to introduce a “cavity” may be referred to as a “hole mutation.” The protuberance is “positionable” in the cavity which means that the spatial location of the protuberance and cavity on the interface of a first polypeptide and second polypeptide respectively and the sizes of the protuberance and cavity are such that the protuberance can be located in the cavity without significantly perturbing the normal association of the first and second polypeptides at the interface. Since protuberances such as Tyr, Phe and Trp do not typically extend perpendicularly from the axis of the interface and have preferred conformations, the alignment of a protuberance with a corresponding cavity may, in some instances, rely on modeling the protuberance / cavity pair based upon a three-dimensional structure such as that obtained by X-ray crystallography or nuclear magnetic resonance (NMR). This can be achieved using widely accepted techniques in the art. In some embodiments, a knob mutation in an IgG1 constant region is T366W (EU numbering). In some embodiments, a hole mutation in an IgG1 constant region comprises one or more mutations selected from T366S, L368A and Y407V (EU numbering). In some embodiments, a hole mutation in an IgG1 constant region comprises T366S, L368A and Y407V (EU numbering). In some embodiments, a knob mutation in an IgG4 constant region is T366W (EU numbering). In some embodiments, a hole mutation in an IgG4 constant region comprises one or more mutations selected from T366S, L368A, and Y407V (EU numbering). In some embodiments, a hole mutation in an IgG4 constant region comprises T366S, L368A, and Y407V (EU numbering). Multi-specific antibodies may also be made by engineering electrostatic steering effects for making antibody Fc-heterodimeric molecules (WO 2009 / 089004A1); cross-linking two or more antibodies or fragments (see, e.g., US Patent No.4,676,980, and Brennan et al., Science, 229: 81 (1985)); using leucine zippers to produce bi-specific antibodies (see, e.g., Kostelny et al., J. Immunol., 148(5):1547-1553 (1992)); using “diabody” technology for making bispecific antibody fragments (see, e.g., Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993)); and using single-chain Fv (sFv) dimers (see,e.g. Gruber et al., J. Immunol., 152:5368 (1994)); and preparing trispecific antibodies as described, e.g., in Tutt et al. J. Immunol.147: 60 (1991). Engineered antibodies with three or more functional antigen binding sites, including “Octopus antibodies,” are also included herein (see, e.g. US 2006 / 0025576A1). The antibody or fragment herein also includes a “Dual Acting FAb” or “DAF” comprising an antigen binding site that binds to the target as well as another, different antigen (see, US 2008 / 0069820, for example). Antibody Variants In certain embodiments, amino acid sequence variants of the antibodies provided herein are contemplated. For example, it may be desirable to improve the binding affinity and / or other biological properties of the antibody. Amino acid sequence variants of an antibody may be prepared by introducing appropriate modifications into the nucleotide sequence encoding the antibody, or by peptide synthesis. Such modifications include, for example, deletions from, and / or insertions into and / or substitutions of residues within the amino acid sequences of the antibody. Any combination of deletion, insertion, and substitution can be made to arrive at the final construct, provided that the final construct possesses the desired characteristics, e.g., antigen-binding. Substitution, Insertion, and Deletion Variants In certain embodiments, antibody variants having one or more amino acid substitutions are provided. Sites of interest for substitutional mutagenesis include the HVRs and FRs. Conservative substitutions are shown in Table 1 under the heading of “preferred substitutions.” More substantial changes are provided in Table 1 under the heading of “exemplary substitutions,” and as further described below in reference to amino acid side chain classes. Amino acid substitutions may be introduced into an antibody of interest and the products screened for a desired activity, e.g., retained / improved antigen binding, decreased immunogenicity, or improved ADCC or CDC. TABLE 1 Amino acids may be grouped according to common side-chain properties: (1) hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that influence chain orientation: Gly, Pro; (6) aromatic: Trp, Tyr, Phe. Non-conservative substitutions will entail exchanging a member of one of these classes for another class. One type of substitutional variant involves substituting one or more hypervariable region residues of a parent antibody (e.g. a humanized or human antibody). Generally, the resulting variant(s) selected for further study will have modifications (e.g., improvements) in certain biological properties (e.g., increased affinity, reduced immunogenicity) relative to the parent antibody and / or will have substantially retained certain biological properties of the parent antibody. An exemplary substitutional variant is an affinity matured antibody, which may be conveniently generated, e.g., using phage display-based affinity maturation techniques such as those described herein. Briefly, one or more HVR residues are mutated and the variant antibodies displayed on phage and screened for a particular biological activity (e.g. binding affinity). Alterations (e.g., substitutions) may be made in HVRs, e.g., to improve antibody affinity. Such alterations may be made in HVR “hotspots,” i.e., residues encoded by codons that undergo mutation at high frequency during the somatic maturation process (see, e.g., Chowdhury, Methods Mol. Biol.207:179-196 (2008)), and / or SDRs (a-CDRs), with the resulting variant VH or VL being tested for binding affinity. Affinity maturation by constructing and reselecting from secondary libraries has been described, e.g., in Hoogenboom et al. in Methods in Molecular Biology 178:1-37 (O’Brien et al., ed., Human Press, Totowa, NJ, (2001).) In some embodiments of affinity maturation, diversity is introduced into the variable genes chosen for maturation by any of a variety of methods (e.g., error-prone PCR, chain shuffling, or oligonucleotide-directed mutagenesis). A secondary library is then created. The library is then screened to identify any antibody variants with the desired affinity. Another method to introduce diversity involves HVR- directed approaches, in which several HVR residues (e.g., 4-6 residues at a time) are randomized. HVR residues involved in antigen binding may be specifically identified, e.g., using alanine scanning mutagenesis or modeling. CDR-H3 and CDR-L3 in particular are often targeted. In certain embodiments, substitutions, insertions, or deletions may occur within one or more HVRs so long as such alterations do not substantially reduce the ability of the antibody to bind antigen. For example, conservative alterations (e.g., conservative substitutions as provided herein) that do not substantially reduce binding affinity may be made in HVRs. Such alterations may be outside of HVR “hotspots” or SDRs. In certain embodiments of the variant VH and VL sequences provided above, each HVR either is unaltered, or contains no more than one, two or three amino acid substitutions. A useful method for identification of residues or regions of an antibody that may be targeted for mutagenesis is called “alanine scanning mutagenesis” as described by Cunningham and Wells (1989) Science, 244:1081-1085. In this method, a residue or group of target residues (e.g., charged residues such as arg, asp, his, lys, and glu) are identified and replaced by a neutral or negatively charged amino acid (e.g., alanine or polyalanine) to determine whether the interaction of the antibody with antigen is affected. Further substitutions may be introduced at the amino acid locations demonstrating functional sensitivity to the initial substitutions. Alternatively, or additionally, a crystal structure of an antigen-antibody complex is used to identify contact points between the antibody and antigen. Such contact residues and neighboring residues may be targeted or eliminated as candidates for substitution. Variants may be screened to determine whether they contain the desired properties. Amino acid sequence insertions include amino- and / or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing a hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Examples of terminal insertions include an antibody with an N-terminal methionyl residue. Other insertional variants of the antibody molecule include the fusion to the N- or C-terminus of the antibody to an enzyme (e.g. for ADEPT) or a polypeptide which increases the serum half-life of the antibody. Glycosylation variants In certain embodiments, an antibody provided herein is altered to increase or decrease the extent to which the antibody is glycosylated. Addition or deletion of glycosylation sites to an antibody may be conveniently accomplished by altering the amino acid sequence such that one or more glycosylation sites is created or removed. Where the antibody comprises an Fc region, the carbohydrate attached thereto may be altered. Native antibodies produced by mammalian cells typically comprise a branched, biantennary oligosaccharide that is generally attached by an N-linkage to Asn297 of the CH2domain of the Fc region. See, e.g., Wright et al. TIBTECH 15:26-32 (1997). The oligosaccharide may include various carbohydrates, e.g., mannose, N-acetyl glucosamine (GlcNAc), galactose, and sialic acid, as well as a fucose attached to a GlcNAc in the “stem” of the biantennary oligosaccharide structure. In some embodiments, modifications of the oligosaccharide in an antibody of the invention may be made in order to create antibody variants with certain improved properties. In one embodiment, antibody variants are provided having a carbohydrate structure that lacks fucose attached (directly or indirectly) to an Fc region. For example, the amount of fucose in such antibody may be from 1% to 80%, from 1% to 65%, from 5% to 65% or from 20% to 40%. The amount of fucose is determined by calculating the average amount of fucose within the sugar chain at Asn297, relative to the sum of all glycostructures attached to Asn 297 (e. g. complex, hybrid and high mannose structures) as measured by MALDI-TOF mass spectrometry, as described in WO 2008 / 077546, for example. Asn297 refers to the asparagine residue located at about position 297 in the Fc region (Eu numbering of Fc region residues); however, Asn297 may also be located about ± 3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300, due to minor sequence variations in antibodies. Such fucosylation variants may have improved ADCC function. See, e.g., US Patent Publication Nos. US 2003 / 0157108 (Presta, L.); US 2004 / 0093621 (Kyowa Hakko Kogyo Co., Ltd). Examples of publications related to “defucosylated” or “fucose-deficient” antibody variants include: US 2003 / 0157108; WO 2000 / 61739; WO 2001 / 29246; US 2003 / 0115614; US 2002 / 0164328; US 2004 / 0093621; US 2004 / 0132140; US 2004 / 0110704; US 2004 / 0110282; US 2004 / 0109865; WO 2003 / 085119; WO 2003 / 084570; WO 2005 / 035586; WO 2005 / 035778; WO2005 / 053742; WO2002 / 031140; Okazaki et al. J. Mol. Biol.336:1239-1249 (2004); Yamane-Ohnuki et al. Biotech. Bioeng.87: 614 (2004). Examples of cell lines capable of producing defucosylated antibodies include Lec13 CHO cells deficient in protein fucosylation (Ripka et al. Arch. Biochem. Biophys.249:533-545 (1986); US Pat Appl No US 2003 / 0157108 A1, Presta, L; and WO 2004 / 056312 A1, Adams et al., especially at Example 11), and knockout cell lines, such as alpha-1,6-fucosyltransferase gene, FUT8, knockout CHO cells (see, e.g., Yamane-Ohnuki et al. Biotech. Bioeng.87: 614 (2004); Kanda, Y. et al., Biotechnol. Bioeng., 94(4):680-688 (2006); and WO2003 / 085107). Antibodies variants are further provided with bisected oligosaccharides, e.g., in which a biantennary oligosaccharide attached to the Fc region of the antibody is bisected by GlcNAc. Such antibody variants may have reduced fucosylation and / or improved ADCC function. Examples of such antibody variants are described, e.g., in WO 2003 / 011878 (Jean-Mairet et al.); US Patent No.6,602,684 (Umana et al.); and US 2005 / 0123546 (Umana et al.). Antibody variants with at least one galactose residue in the oligosaccharide attached to the Fc region are also provided. Such antibody variants may have improved CDC function. Such antibody variants are described, e.g., in WO 1997 / 30087 (Patel et al.); WO 1998 / 58964 (Raju, S.); and WO 1999 / 22764 (Raju, S.). Fc region variants In certain embodiments, one or more amino acid modifications may be introduced into the Fc region of an antibody provided herein, thereby generating an Fc region variant. The Fc region variant may comprise a human Fc region sequence (e.g., a human IgG1, IgG2, IgG3 or IgG4 Fc region) comprising an amino acid modification (e.g. a substitution) at one or more amino acid positions. In certain embodiments, the invention contemplates an antibody variant that possesses some but not all effector functions, which make it a desirable candidate for applications in which the half life of the antibody in vivo is important yet certain effector functions (such as complement and ADCC) are unnecessary or deleterious. In vitro and / or in vivo cytotoxicity assays can be conducted to confirm the reduction / depletion of CDC and / or ADCC activities. For example, Fc receptor (FcR) binding assays can be conducted to ensure that the antibody lacks FcγR binding (hence likely lacking ADCC activity), but retains FcRn binding ability. The primary cells for mediating ADCC, NK cells, express Fc(RIII only, whereas monocytes express Fc(RI, Fc(RII and Fc(RIII. FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol.9:457-492 (1991). Non-limiting examples of in vitro assays to assess ADCC activity of a molecule of interest is described in U.S. Patent No.5,500,362 (see, e.g. Hellstrom, I. et al. Proc. Nat’l Acad. Sci. USA 83:7059-7063 (1986)) and Hellstrom, I et al., Proc. Nat’l Acad. Sci. USA 82:1499-1502 (1985); 5,821,337 (see Bruggemann, M. et al., J. Exp. Med.166:1351-1361 (1987)). Alternatively, non-radioactive assays methods may be employed (see, for example, ACTI™ non-radioactive cytotoxicity assay for flow cytometry (CellTechnology, Inc. Mountain View, CA; and CytoTox 96®non-radioactive cytotoxicity assay (Promega, Madison, WI). Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells. Alternatively, or additionally, ADCC activity of the molecule of interest may be assessed in vivo, e.g., in a animal model such as that disclosed in Clynes et al. Proc. Nat’l Acad. Sci. USA 95:652-656 (1998). C1q binding assays may also be carried out to confirm that the antibody is unable to bind C1q and hence lacks CDC activity. See, e.g., C1q and C3c binding ELISA in WO 2006 / 029879 and WO 2005 / 100402. To assess complement activation, a CDC assay may be performed (see, for example, Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996); Cragg, M.S. et al., Blood 101:1045-1052 (2003); and Cragg, M.S. and M.J. Glennie, Blood 103:2738-2743 (2004)). FcRn binding and in vivo clearance / half life determinations can also be performed using methods known in the art (see, e.g., Petkova, S.B. et al., Int’l. Immunol.18(12):1759-1769 (2006)). In some embodiments, one or more amino acid modifications may be introduced into the Fc portion of the antibody provided herein in order to increase IgG binding to the neonatal Fc receptor. In certain embodiments, the antibody comprises the following three mutations according to EU numbering: M252Y, S254T, and T256E (the “YTE mutation”) (US Patent No. 8,697,650; see also Dall’Acqua et al., Journal of Biological Chemistry 281(33):23514-23524 (2006). In certain embodiments, the YTE mutation does not affect the ability of the antibody to bind to its cognate antigen. In certain embodiments, the YTE mutation increases the antibody’s serum half-life compared to the native (i.e., non-YTE mutant) antibody. In some embodiments, the YTE mutation increases the serum half-life of the antibody by 3-fold compared to the native (i.e., non-YTE mutant) antibody. In some embodiments, the YTE mutation increases the serum half-life of the antibody by 2-fold compared to the native (i.e., non-YTE mutant) antibody. In some embodiments, the YTE mutation increases the serum half-life of the antibody by 4-fold compared to the native (i.e., non-YTE mutant) antibody. In some embodiments, the YTE mutation increases the serum half-life of the antibody by at least 5-fold compared to the native (i.e., non-YTE mutant) antibody. In some embodiments, the YTE mutation increases the serum half-life of the antibody by at least 10-fold compared to the native (i.e., non-YTE mutant) antibody. See, e.g., US Patent No.8,697,650; see also Dall’Acqua et al., Journal of Biological Chemistry 281(33):23514-23524 (2006). In certain embodiments, the YTE mutant provides a means to modulate antibody- dependent cell-mediated cytotoxicity (ADCC) activity of the antibody. In certain embodiments, the YTEO mutant provides a means to modulate ADCC activity of a humanized IgG antibody directed against a human antigen. See, e.g., US Patent No.8,697,650; see also Dall’Acqua et al., Journal of Biological Chemistry 281(33):23514-23524 (2006). In certain embodiments, the YTE mutant allows the simultaneous modulation of serum half-life, tissue distribution, and antibody activity (e.g., the ADCC activity of an IgG antibody). See, e.g., US Patent No.8,697,650; see also Dall’Acqua et al., Journal of Biological Chemistry 281(33):23514-23524 (2006). Antibodies with reduced effector function include those with substitution of one or more of Fc region residues 238, 265, 269, 270, 297, 327 and 329 (U.S. Patent No.6,737,056). Such Fc mutants include Fc mutants with substitutions at two or more of amino acid positions 265, 269, 270, 297 and 327, including the so-called “DANA” Fc mutant with substitution of residues 265 and 297 to alanine (US Patent No.7,332,581). In certain embodiments, the proline at position329 (EU numbering ) (P329) of a wild-type human Fc region is substituted with glycine or arginine or an amino acid residue large enough to destroy the proline sandwich within the Fc / Fc gamma receptor interface, that is formed between the P329 of the Fc and tryptophane residues W87 and W110 of FcgRIII (Sondermann et al.: Nature 406, 267-273 (20 July 2000)). In a further embodiment, at least one further amino acid substitution in the Fc variant is S228P, E233P, L234A, L235A, L235E, N297A, N297D, or P331S and still in another embodiment said at least one further amino acid substitution is L234A and L235A of the human IgG1 Fc region or S228P and L235E of the human IgG4 Fc region, all according to EU numbering (U.S. Patent No.8,969,526 which is incorporated by reference in its entirety). In certain embodiments, a polypeptide comprises the Fc variant of a wild-type human IgG Fc region wherein the polypeptide has P329 of the human IgG Fc region substituted with glycine and wherein the Fc variant comprises at least two further amino acid substitutions at L234A and L235A of the human IgG1 Fc region or S228P and L235E of the human IgG4 Fc region, and wherein the residues are numbered according to the EU numbering (U.S. Patent No.8,969,526 which is incorporated by reference in its entirety). In certain embodiments, the polypeptide comprising the P329G, L234A and L235A (EU numbering) substitutions exhibit a reduced affinity to the human FcγRIIIA and FcγRIIA, for down-modulation of ADCC to at least 20% of the ADCC induced by the polypeptide comprising the wildtype human IgG Fc region, and / or for down-modulation of ADCP (U.S. Patent No.8,969,526 which is incorporated by reference in its entirety). In a specific embodiment the polypeptide comprising an Fc variant of a wildtype human Fc polypeptide comprises a triple mutation: an amino acid substitution at position Pro329, a L234A and a L235A mutation according to EU numbering (P329 / LALA) (U.S. Patent No. 8,969,526 which is incorporated by reference in its entirety). In specific embodiments, the polypeptide comprises the following amino acid substitutions: P329G, L234A, and L235A according to EU numbering. Certain antibody variants with improved or diminished binding to FcRs are described. (See, e.g., U.S. Patent No.6,737,056; WO 2004 / 056312, and Shields et al., J. Biol. Chem.9(2): 6591-6604 (2001).) In certain embodiments, an antibody variant comprises an Fc region with one or more amino acid substitutions which improve ADCC, e.g., substitutions at positions 298, 333, and / or 334 of the Fc region (EU numbering of residues). In some embodiments, alterations are made in the Fc region that result in altered (i.e., either improved or diminished) C1q binding and / or Complement Dependent Cytotoxicity (CDC), e.g., as described in US Patent No.6,194,551, WO 99 / 51642, and Idusogie et al. J. Immunol.164: 4178-4184 (2000). Antibodies with increased half lives and improved binding to the neonatal Fc receptor (FcRn), which is responsible for the transfer of maternal IgGs to the fetus (Guyer et al., J. Immunol.117:587 (1976) and Kim et al., J. Immunol.24:249 (1994)), are described in US2005 / 0014934A1 (Hinton et al.). Those antibodies comprise an Fc region with one or more substitutions therein which improve binding of the Fc region to FcRn. Such Fc variants include those with substitutions at one or more of Fc region residues: 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434, e.g., substitution of Fc region residue 434 (US Patent No.7,371,826). See also Duncan & Winter, Nature 322:738-40 (1988); U.S. Patent No.5,648,260; U.S. Patent No.5,624,821; and WO 94 / 29351 concerning other examples of Fc region variants. Cysteine engineered antibody variants In certain embodiments, it may be desirable to create cysteine engineered antibodies, e.g., a “THIOMAB™” or TDC, in which one or more residues of an antibody are substituted with cysteine residues. In particular embodiments, the substituted residues occur at sites of the antibody that are available for conjugation. By substituting those residues with cysteine, reactive thiol groups are thereby positioned at accessible sites of the antibody and may be used to conjugate the antibody to other moieties, such as drug moieties or linker-drug moieties, to create an immunoconjugate, as described further herein. In certain embodiments, any one or more of the following residues may be substituted with cysteine: K149 (Kabat numbering) of the light chain; V205 (Kabat numbering) of the light chain; A118 (EU numbering) of the heavy chain; A140 (EU numbering) of the heavy chain; L174 (EU numbering) of the heavy chain; Y373 (EU numbering) of the heavy chain; and S400 (EU numbering) of the heavy chain Fc region. In specific embodiments, the antibodies described herein comprise the HC-A140C (EU numbering) cysteine substitution. In specific embodiments, the antibodies described herein comprise the LC-K149C (Kabat numbering) cysteine substitution. In specific embodiments, the antibodies described herein comprise the HC-A118C (EU numbering) cysteine substitution. Cysteine engineered antibodies may be generated as described, e.g., in U.S. Patent No.7,521,541. Antibody Derivatives In certain embodiments, an antibody provided herein may be further modified to contain additional nonproteinaceous moieties that are known in the art and readily available. The moieties suitable for derivatization of the antibody include but are not limited to water soluble polymers. Non-limiting examples of water soluble polymers include, but are not limited to, polyethylene glycol (PEG), copolymers of ethylene glycol / propylene glycol, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1, 3-dioxolane, poly-1,3,6-trioxane, ethylene / maleic anhydride copolymer, polyaminoacids (either homopolymers or random copolymers), and dextran or poly(n-vinyl pyrrolidone)polyethylene glycol, propylene glycol homopolymers, polypropylene oxide / ethylene oxide co-polymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde may have advantages in manufacturing due to its stability in water. The polymer may be of any molecular weight, and may be branched or unbranched. The number of polymers attached to the antibody may vary, and if more than one polymer is attached, they can be the same or different molecules. In general, the number and / or type of polymers used for derivatization can be determined based on considerations including, but not limited to, the particular properties or functions of the antibody to be improved, whether the antibody derivative will be used in a therapy under defined conditions, etc. In another embodiment, conjugates of an antibody and nonproteinaceous moiety that may be selectively heated by exposure to radiation are provided. In one embodiment, the nonproteinaceous moiety is a carbon nanotube (Kam et al., Proc. Natl. Acad. Sci. USA 102: 11600-11605 (2005)). The radiation may be of any wavelength, and includes, but is not limited to, wavelengths that do not harm ordinary cells, but which heat the nonproteinaceous moiety to a temperature at which cells proximal to the antibody-nonproteinaceous moiety are killed. Recombinant Methods and Compositions Antibodies may be produced using recombinant methods and compositions, e.g., as described in U.S. Patent No.4,816,567. In one embodiment, isolated nucleic acid encoding an antibody described herein is provided. Such nucleic acid may encode an amino acid sequence comprising the VL and / or an amino acid sequence comprising the VH of the antibody (e.g., the light and / or heavy chains of the antibody). In a further embodiment, one or more vectors (e.g., expression vectors) comprising such nucleic acid are provided. In a further embodiment, a host cell comprising such nucleic acid is provided. In one such embodiment, a host cell comprises (e.g., has been transformed with): (1) a vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antibody and an amino acid sequence comprising the VH of the antibody, or (2) a first vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antibody and a second vector comprising a nucleic acid that encodes an amino acid sequence comprising the VH of the antibody. In one embodiment, the host cell is eukaryotic, e.g. a Chinese Hamster Ovary (CHO) cell or lymphoid cell (e.g., Y0, NS0, Sp20 cell). In one embodiment, a method of making an antibody is provided, wherein the method comprises culturing a host cell comprising a nucleic acid encoding the antibody, as provided above, under conditions suitable for expression of the antibody, and optionally recovering the antibody from the host cell (or host cell culture medium). For recombinant production of an antibody, nucleic acid encoding an antibody, e.g., as described above, is isolated and inserted into one or more vectors for further cloning and / or expression in a host cell. Such nucleic acid may be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the antibody). Suitable host cells for cloning or expression of antibody-encoding vectors include prokaryotic or eukaryotic cells described herein. For example, antibodies may be produced in bacteria, in particular when glycosylation and Fc effector function are not needed. For expression of antibody fragments and polypeptides in bacteria, see, e.g., U.S. Patent Nos.5,648,237, 5,789,199, and 5,840,523. (See also Charlton, Methods in Molecular Biology, Vol.248 (B.K.C. Lo, ed., Humana Press, Totowa, NJ, 2003), pp.245-254, describing expression of antibody fragments in E. coli.) After expression, the antibody may be isolated from the bacterial cell paste in a soluble fraction and can be further purified. In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for antibody-encoding vectors, including fungi and yeast strains whose glycosylation pathways have been “humanized,” resulting in the production of an antibody with a partially or fully human glycosylation pattern. See Gerngross, Nat. Biotech. 22:1409-1414 (2004), and Li et al., Nat. Biotech.24:210-215 (2006). Suitable host cells for the expression of glycosylated antibody are also derived from multicellular organisms (invertebrates and vertebrates). Examples of invertebrate cells include plant and insect cells. Numerous baculoviral strains have been identified which may be used in conjunction with insect cells, particularly for transfection of Spodoptera frugiperda cells. Plant cell cultures can also be utilized as hosts. See, e.g., US Patent Nos.5,959,177, 6,040,498, 6,420,548, 7,125,978, and 6,417,429 (describing PLANTIBODIESTMtechnology for producing antibodies in transgenic plants). Vertebrate cells may also be used as hosts. For example, mammalian cell lines that are adapted to grow in suspension may be useful. Other examples of useful mammalian host cell lines are monkey kidney CV1 line transformed by SV40 (COS-7); human embryonic kidney line (293 or 293 cells as described, e.g., in Graham et al., J. Gen Virol.36:59 (1977); baby hamster kidney cells (BHK); mouse sertoli cells (TM4 cells as described, e.g., in Mather, Biol. Reprod. 23:243-251 (1980); monkey kidney cells (CV1); African green monkey kidney cells (VERO-76); human cervical carcinoma cells (HELA); canine kidney cells (MDCK; buffalo rat liver cells (BRL 3A); human lung cells (W138); human liver cells (Hep G2); mouse mammary tumor (MMT 060562); TRI cells, as described, e.g., in Mather et al., Annals N.Y. Acad. Sci.383:44-68 (1982); MRC 5 cells; and FS4 cells. Other useful mammalian host cell lines include Chinese hamster ovary (CHO) cells, including DHFR- CHO cells (Urlaub et al., Proc. Natl. Acad. Sci. USA 77:4216 (1980)); and myeloma cell lines such as Y0, NS0 and Sp2 / 0. For a review of certain mammalian host cell lines suitable for antibody production, see, e.g., Yazaki and Wu, Methods in Molecular Biology, Vol.248 (B.K.C. Lo, ed., Humana Press, Totowa, NJ), pp.255-268 (2003). ANTIBODY-DRUG CONJUGATES (ADC) The antibody-drug conjugate (ADC) compounds of the invention comprise an antibody specific for a tumor-associated antigen covalently attached, linked to a potent toxin It is to be understood that where more than one nucleophilic lysine nitrogen (e.g., sidechain amine nitrogen) or cysteine thiol group of an antibody reacts with a drug-linker intermediate or linker reagent, then the resulting product is a mixture of ADC compounds with a distribution of one or more drug moieties attached to an antibody. The average number of drugs per antibody (DAR) may be calculated from the mixture by a dual ELISA antibody assay, which is specific for antibody and specific for the drug. Individual ADC molecules may be identified in the mixture by mass spectroscopy and separated by HPLC, e.g. hydrophobic interaction chromatography (see, e.g., McDonagh et al (2006) Prot. Engr. Design & Selection 19(7):299-307; Hamblett et al (2004) Clin. Cancer Res.10:7063-7070; Hamblett, K.J., et al. “Effect of drug loading on the pharmacology, pharmacokinetics, and toxicity of an anti-CD30 antibody-drug conjugate,” Abstract No.624, American Association for Cancer Research, 2004 Annual Meeting, March 27-31, 2004, Proceedings of the AACR, Volume 45, March 2004; Alley, S.C., et al. “Controlling the location of drug attachment in antibody-drug conjugates,” Abstract No.627, American Association for Cancer Research, 2004 Annual Meeting, March 27-31, 2004, Proceedings of the AACR, Volume 45, March 2004). In certain embodiments, a homogeneous ADC with a single loading value may be isolated from the conjugation mixture by electrophoresis or chromatography. A linker is a bifunctional or multifunctional compound which can be used to link an active agent (e.g., a drug) and an antibody to form an antibody-drug conjugate (ADC). Such conjugates are useful, for example, in the formation of immunoconjugates directed against tumor associated antigens. Such conjugates allow the selective delivery of cytotoxic drugs to tumor cells. In an ADC, the linker serves to attach the toxin to the antibody. The linker can also link an active agent to a reactive group, wherein the reactive group can react with an antibody to form the ADC. The “Linker” (L) is a bifunctional or multifunctional moiety that can be used to link one or more toxin drug moieties to an antibody (Ab) to form the antibody-drug conjugate (ADC) of Formula III. In some embodiments, antibody-drug conjugates (ADC) can be prepared using a linker having reactive functionalities for covalently attaching to the drug and to the antibody. For example, in some embodiments, a side chain amine of a lysine of an antibody (Ab) can form a bond with a reactive functional group of a linker or a drug-linker intermediate to make an ADC. In another example, a cysteine thiol of an antibody (Ab) can form a bond with a reactive functional group of a linker or a drug-linker intermediate of to make an ADC. The Linker L is covalently bound via one reactive site of a bifunctional compound, leaving the other functional site available for subsequent attachment to an antibody. The Linker L is a moiety having 1-200 non-hydrogen atoms selected from C, N, O, S, or halogen, and optionally incorporates ether, oxo, carboxyl, carboxamide, carboxamidyl, urethanyl, branched, cyclic, unsaturated, amino acid, heterocyclic, aromatic or heteroaromatic moieties. Linker L may be unbranched or branched, flexible or rigid, short or long and may incorporate any combination of moieties as deemed useful. In some embodiments, at least a portion of the linker L may have a polyalkylene oxide polymeric region, which may enhance solubility of the compound. In some embodiments, the Linker L may have a repeating unit of ethylene glycol, and may have a number of repeating ethylene glycol units of about 1 to about 25, or any number there between. In some embodiments, L may include about 1 to about 4, about 3 to about 20, about 4 to about 15, about 5 to about 12 or about 6 to about 10 ethylene glycol units. In some embodiments, at least a portion of Linker L may include one or more amino acid moieties which may provide enhanced solubility for the compound or may provide amino acid sequences to enhance target binding, enhance compatibility with a target binding agent, or enhance target binding recognition. In other embodiments, the Linker L may include one or more amino acid moieties that provide a suitable substrate motif for a protease. Such embodiments include amino acids selected from glycine, alanine, phenylalanine, lysine, arginine, valine, and citrulline. When a set of amino acid moieties are incorporated into the linker L that provide a substrate motif specific for a selected protease, the cytotoxic drug compound may be released from a target bound conjugate to provide localized cytotoxic effects. Such substrate motifs are known in the art and may be incorporated into the Linker L as desired to provide selective release from the target bound conjugate. This selectivity can be based on known presence of a desired protease within the localized delivery region of the drug-antibody conjugate. Other polymeric types of moieties may be incorporated in the Linker L, such as polyacids, polysaccharides, or polyamines. Other moieties such as substituted aromatic or heteroaromatic moieties may be used to enhance rigidity or provide synthetically accessible sites on substituents therein for linking to reactive moieties or to the compound. The other second functional site of Linker L is available for subsequent attachment to an antibody, thus covalently bonding the toxin of the invention to an antibody via a linker. This second reactive site is, for example, an electrophilic group that is reactive to a nucleophilic group present on an antibody unit (e.g., an antibody). Useful nucleophilic groups on an antibody include but are not limited to, sulfhydryl, hydroxyl and amino groups. The heteroatom of the nucleophilic group of an antibody is reactive to an electrophilic group on a linker unit and forms a covalent bond to a linker unit. Useful electrophilic groups include, but are not limited to, maleimide and haloacetamide groups. The electrophilic group provides a convenient site for antibody attachment. In another embodiment, a linker unit has a reactive site which has a nucleophilic group that is reactive to an electrophilic group present on an antibody. Useful electrophilic groups on an antibody include, but are not limited to, aldehyde and ketone carbonyl groups. The heteroatom of a nucleophilic group of a linker unit can react with an electrophilic group on an antibody and form a covalent bond to the antibody. Useful nucleophilic groups on a linker unit include, but are not limited to, hydrazide, oxime, amino, hydrazine, thiosemicarbazone, hydrazine carboxylate, and arylhydrazide. The electrophilic group on an antibody provides a convenient site for attachment to a linker unit. In some embodiments, the electrophilic groups include: where the wavy lines indicate the attachments to L, and R4is NO2, Cl, F, CN, or Br, and q is 0, 1, or 2. Amino functional groups are also useful reactive sites for a linker unit because they can react with carboxylic acid, or activated esters of a compound to form an amide linkage. Typically, the peptide-based compounds of the invention can be prepared by forming a peptide bond between two or more amino acids and / or peptide fragments. In one aspect, a linker has a functionality that is capable of reacting with a free cysteine present on an antibody to form a covalent bond. Nonlimiting examples of such reactive functionalities include maleimide, haloacetamides, α-haloacetyl, pyridyl disulfide, activated esters such as succinimide esters, N-hydroxysuccinimide, 4-nitrophenyl esters, pentafluorophenyl esters, tetrafluorophenyl esters, anhydrides, acid chlorides, sulfonyl chlorides, isocyanates, and isothiocyanates. See, e.g., the conjugation method at page 766 of Klussman, et al., Bioconjugate Chemistry, 2004, 15(4):765-773, and the Examples herein. In some embodiments, a linker has a functionality that is capable of reacting with an electrophilic group present on an antibody. Examples of such electrophilic groups include, but are not limited to, aldehyde and ketone carbonyl groups. In some embodiments, a heteroatom of the reactive functionality of the linker can react with an electrophilic group on an antibody and form a covalent bond to an antibody unit. Nonlimiting examples of reactive functionalities include, but are not limited to, hydrazide, oxime, amino, hydrazine, thiosemicarbazone, hydrazine carboxylate, and arylhydrazide. A linker may comprise one or more linker components, including but not limited to, a stretcher unit, a peptidomimetic unit, a peptide unit, and a spacer unit. See J. Lu., et al. (Int. J. Mol. Sci., 2016, 17:561). Exemplary linker components and linker reagents include, but are not limited to, p-amino benzoic acid-valine-citrulline (“PABA-val-cit”), 6- maleimidocaproyl (“MC”), maleimidopropanoyl (“MP”), valine-citrulline (“val-cit” or “vc”), valine-alanine (“val-ala” or “va”), alanine-phenylalanine (“ala-phe”), phenylalanine-lysine (phe-lys), glycine-phenylalanine-leucine-glycine (“GFLG”), p-aminobenzyloxycarbonyl (“PAB”), N-succinimidyl 4-(2-pyridylthio) pentanoate (“SPP”), 4-(N-maleimidomethyl) cyclohexane-1 carboxylate (“MCC”), 4-(N-maleimidomethyl)cyclohexanecarboxylic acid N- hydroxysuccinimide ester (“SMCC”), N-succinimidyl 4-(2-pyridyldithio)butanoate (“SPDB”), and sulfo-N-succinimidyl 4-(2-pyridyldithio)butyrate (“sulfo-SPDB”). Various linker components are known in the art, which are described herein. Exemplary linker components include, but are not limited to, “VC-2xPEG”, “VA-2xPEG”, and “VC-8xPEG”, and “VA-8xPEG”, where a valine-citrulline unit is attached to two or more ethyleneoxy units (PEG), for example, two to 10 PEG units. A linker may be a “cleavable linker,” facilitating release of a drug or toxin. Nonlimiting examples of cleavable linkers include acid-labile linkers (e.g., comprising hydrazone), protease-sensitive (e.g., peptidase-sensitive) linkers, photolabile linkers, or disulfide- containing linkers (Chari, et al., Cancer Research, 1992, 52:127-131; U.S. Patent No. 5,208,020). Further examples of embodiments of linkers are described in U.S. Patent No. 7,498,298, which is expressly incorporated herein by reference. One embodiment provides an antibody-drug conjugate compound comprising an antibody covalently attached to a drug moiety directly (i.e., without a linker) or through a linker of Formula I: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein the drug moiety is: L is a linker; n is 0 or 1; p is 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10); and Ab is an antibody. One embodiment provides an antibody-drug conjugate compound comprising an antibody covalently attached to a drug moiety directly (i.e., without a linker) or through a linker of Formula I: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein the drug moiety is: L is a linker; n is 0 or 1; p is 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10); and Ab is an antibody that binds to Trop2. One embodiment provides an antibody-drug conjugate compound comprising an antibody covalently attached to a drug moiety directly (i.e., without a linker) or through a linker of Formula I: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein L is a linker; n is 0 or 1; p is 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10); and Ab is an antibody that binds to Trop2. One embodiment provides an antibody-drug conjugate comprising an anti-Trop2 antibody covalently attached to one or more a drug moieties of formula II: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof). One embodiment provides an antibody-drug conjugate comprising an antibody covalently attached to one or more a drug moieties of formula II: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof). One embodiment provides an antibody-drug conjugate (or a mixture of antibody-drug conjugates) comprising an anti-Trop2 antibody covalently attached to one or more a drug moieties of formula II: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein the average DAR (drug antibody ratio) is 1-15, 1-12, 1-10, 1-8, 1-6, 1-5, 1-4, 1-3, 2-15, 2-12, 2-10, 2-8, 2-6, 2-5, 2-4, 2-3, 3-15, 3-12, 3-10, 3-8, 3-6, 3-5, or 3-4. One embodiment provides an antibody-drug conjugate (or a mixture of antibody-drug conjugates) comprising an antibody covalently attached to one or more a drug moieties of formula II: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein the average DAR (drug antibody ratio) is 1-15, 1-12, 1-10, 1-8, 1-6, 1-5, 1-4, 1-3, 2-15, 2-12, 2-10, 2-8, 2-6, 2-5, 2-4, 2-3, 3-15, 3-12, 3-10, 3-8, 3-6, 3-5, or 3-4. One embodiment provides an antibody-drug conjugate compound comprising an antibody covalently attached to a drug moiety directly of Formula Ia: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein the drug moiety is: p is 1-20 or 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10); and Ab is an anit-Trop2 antibody. One embodiment provides an antibody-drug conjugate compound comprising an antibody covalently attached to a drug moiety directly of Formula Ia: Ia or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein the drug moiety is: p is 1-20 or 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10); and Ab is antibody. One embodiment provides an antibody-drug conjugate compound comprising an antibody covalently attached to a drug moiety directly of Formula Ib: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein p is 1-20 or 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10); and -NHAb* is an anti-Trop2 antibody, wherein the each -NH- is a sidechain amine of a lysine residue of the antibody. One embodiment provides an antibody-drug conjugate compound comprising an antibody covalently attached to a drug moiety directly of Formula Ib: or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein p is 1-20 or 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10); and -NHAb* is an antibody, wherein the each -NH- is a sidechain amine of a lysine residue of the antibody. In one embodiment L is 0. In one embodiment L is absent (i.e., n is 0). In one embodiment antibody is attached to the drug moiety by a sidechain nitrogen of a lysine residue of the antibody. In one embodiment antibody is attached to the drug moiety by a sidechain sulfur of a cysteine residue of the antibody. In one embodiment antibody is attached to the drug moiety by a sidechain nitrogen of an amino acid residue of the antibody. In one embodiment antibody is attached to the drug moiety by a sidechain sulfur of an amino acid residue of the antibody. In one embodiment n is 1. In one embodiment the linker L has the formula -X1-X2-X3-X4- wherein, X1is a bond, -N(Ra)-, -N(Ra)-N(Ra)-, -O-, -N-O-, -S-, -C(=O)-, -C(=O)N(Ra), C(=S)N(Ra)-, -C(=O)O-, -C(=O)S-, -N(Ra)SO2-, -OC(=O)N(Ra)-, -(Ra)HC(=O)N(Ra)-, or -N(Ra)C(=S)N(Ra)-, wherein Rais H or (C1-C6)alkyl; X2is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), -N(Rb)-, a divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl wherein Rbis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S), and wherein the divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl is optionally substituted with one more halo or (C1-C6)alkyl; X3is a bond or a peptide (e.g., a peptide comprising 1, 2, 3, 4, 5, or 6 amino acid residues); and X4is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), or -N(Rc)- wherein Rcis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S); wherein at least one of X1, X2, or X3is not a bond. In one embodiment L has the formula -X1-X2-X3-X4- wherein, X1is a bond, -N(Ra)-, -N(Ra)-N(Ra)-, -O-, -N-O-, -S-, -C(=O)-, -C(=O)N(Ra), C(=S)N(Ra)-, -C(=O)O-, -C(=O)S-, -N(Ra)SO2-, -OC(=O)N(Ra)-, -(Ra)HC(=O)N(Ra)-, or -N(Ra)C(=S)N(Ra)-, wherein Rais H or (C1-C6)alkyl; X2is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), -N(Rb)-, a divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl wherein Rbis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S), and wherein the divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl is optionally substituted with one more halo or (C1-C6)alkyl; X3is a bond or a peptide (e.g., a peptide comprising 1, 2, 3, 4, 5, or 6 amino acid residues); and X4is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), or -N(Rc)- wherein Rcis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S). In one embodiment L has the formula -X1-X2-X3-X4- wherein, X1is a bond, -N(Ra)-, -N(Ra)-N(Ra)-, -O-, -N-O-, -S-, -C(=O)-, -C(=O)N(Ra), C(=S)N(Ra)-, -C(=O)O-, -C(=O)S-, -N(Ra)SO2-, -OC(=O)N(Ra)-, -(Ra)HC(=O)N(Ra)-, or -N(Ra)C(=S)N(Ra)-, wherein Rais H or (C1-C6)alkyl; X2is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), -N(Rb)-, a divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl wherein Rbis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S), and wherein the divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl is optionally substituted with one more halo or (C1-C6)alkyl; X3is a bond or a peptide (e.g., a peptide comprising 1, 2, 3, 4, 5, or 6 amino acid residues); and X4is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 60 carbon atoms (or 2-50, 2-40, 5 -60, 5-50, 5-0, 5-30, or 5-20 carbon atoms), wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), or -N(Rc)- wherein Rcis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S); wherein at least one of X1, X2, or X3is not a bond. In one embodiment n is 0 (i.e., L is absent) or n is 1 and L is a linker selected from the group consisting of: , , and , wherein: each m is independently 1, 2, 3, or 4; each n1 is independently 1, 2, 3, 4, 5, or 6; each p1 is independently 1, 2, 3, 4, 5, or 6; each t is independently 1, 2, 3, or 4; each n2 is independently 1, 2, 3, 4, 5, or 6; each p2 is independently 1, 2, 3, 4, 5,6, 7, 8, 9, or 10; each q2 is independently 1, 2, 3, 4, 5, or 6; each s is independently 1, 2, 3, or 4; and each AA1 and AA2 are independently a sidechain of an amino acid. In one embodiment each m is independently 1, 2, 3, 4, 5, or 6; each n1 is independently 1, 2, 3, 4, 5, 6, 7 or 8; each p1 is independently 1, 2, 3, 4, 5, 6, 7 or 8; each t is independently 1, 2, 3, 4, 5, 6, 7 or 8; each n2 is independently 1, 2, 3, 4, 5, 6, 7 or 8; each p2 is independently 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, or 12; each q2 is independently 1, 2, 3, 4, 5, or 6; each s is independently 1, 2, 3, 4, 5, or 6; and each AA1 and AA2 are independently a sidechain of an amino acid. In one embodiment n is 0 (i.e., L is absent) or n is 1 and L is a linker selected from the group consisting of: , , , , . In one embodiment n is 0 (i.e., L is absent) or n is 1 and L is a linker selected from the group consisting of: . One embodiment provides a compound of formula II or a salt thereof, wherein W is a leaving group or -L-X; L is a linker; and X is a reactive group. In one embodiment W is a leaving group. In one embodiment the leaving group is halo, -O(C1-C6)alkyl, -Oaryl, -Oheteroaryl or -Oheterocylcylyl, wherein the -O(C1-C6)alkyl, -Oaryl, Oheteroaryl or Oheterocylcylyl are each optionally substituted with one or more substituents independently selected from the group consisting of oxo, halo, (C1-C6)alkyl and -O(C1-C6)alkyl, In one embodiment W together with the carbonyl group to which it is attached forms an activated ester. In one embodiment W is -Ophenyl optionally substituted with one or more halo or 2,5, dioxopyrollidinyloxy. In one embodiment W is -Ophenyl optionally substituted with one or more halo. In one embodiment W is -Ophenyl optionally substituted with one or more fluoro. In one embodiment W is a 2,3,5,6,-tetrafluorophenoxy. In one embodiment W is 2,5, dioxopyrollidinyloxy. In one embodiment W is L-X . In one embodiment L has the formula -X1-X2-X3-X4- wherein, X1is a bond, -N(Ra)-, -N(Ra)-N(Ra)-, -O-, -N-O-, -S-, -C(=O)-, -C(=O)N(Ra), C(=S)N(Ra)-, -C(=O)O-, -C(=O)S-, -N(Ra)SO2-, -OC(=O)N(Ra)-, -(Ra)HC(=O)N(Ra)-, or -N(Ra)C(=S)N(Ra)-, wherein Rais H or (C1-C6)alkyl; X2is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), -N(Rb)-, a divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl wherein Rbis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S), and wherein the divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl is optionally substituted with one more halo or (C1-C6)alkyl; X3is a bond or a peptide (e.g., a peptide comprising 1, 2, 3, 4, 5, or 6 amino acid residues); and X4is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), or -N(Rc)- wherein Rcis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S); wherein at least one of X1, X2, or X3is not a bond. In one embodiment L has the formula -X1-X2-X3-X4- wherein, X1is a bond, -N(Ra)-, -N(Ra)-N(Ra)-, -O-, -N-O-, -S-, -C(=O)-, -C(=O)N(Ra), C(=S)N(Ra)-, -C(=O)O-, -C(=O)S-, -N(Ra)SO2-, -OC(=O)N(Ra)-, -(Ra)HC(=O)N(Ra)-, or -N(Ra)C(=S)N(Ra)-, wherein Rais H or (C1-C6)alkyl; X2is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), -N(Rb)-, a divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl wherein Rbis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S), and wherein the divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl is optionally substituted with one more halo or (C1-C6)alkyl; X3is a bond or a peptide (e.g., a peptide comprising 1, 2, 3, 4, 5, or 6 amino acid residues); and X4is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), or -N(Rc)- wherein Rcis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S). In one embodiment L has the formula -X1-X2-X3-X4- wherein, X1is a bond, -N(Ra)-, -N(Ra)-N(Ra)-, -O-, -N-O-, -S-, -C(=O)-, -C(=O)N(Ra), C(=S)N(Ra)-, -C(=O)O-, -C(=O)S-, -N(Ra)SO2-, -OC(=O)N(Ra)-, -(Ra)HC(=O)N(Ra)-, or -N(Ra)C(=S)N(Ra)-, wherein Rais H or (C1-C6)alkyl; X2is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms (or 2-30, 2-20, 5-30, or 5-20 carbon atoms), wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), - N(Rb)-, a divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl wherein Rbis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S), and wherein the divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl is optionally substituted with one more halo or (C1-C6)alkyl; X3is a bond or a peptide (e.g., a peptide comprising 1, 2, 3, 4, 5, or 6 amino acid residues); and X4is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 60 (or 2-50, 2-40, 5 -60, 5-50, 5-40, 5-30, or 5-20 carbon atoms), wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), or -N(Rc)- wherein Rcis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S); wherein at least one of X1, X2, or X3is not a bond. In on embodiment the amino acid residue is a residue of a natural amino acid or citrulline. In on embodiment the amino acid residue is a residue of a natural amino acid or citrulline or a stereisomer thereof. In one embodiment the amino acid residue is a alanine, glycine, valine or citrulline residue. In one embodiment W is selected from the group consisting of . , wherein: each m is independently 1, 2, 3, or 4; each n1 is independently 1, 2, 3, 4, 5, or 6; each p1 is independently 1, 2, 3, 4, 5, or 6; each t is independently 1, 2, 3, or 4; each n2 is independently 1, 2, 3, 4, 5, or 6; each p2 is independently 1, 2, 3, 4, 5,6, 7, 8, 9, or 10; each q2 is independently 1, 2, 3, 4, 5, or 6; each s is independently 1, 2, 3, or 4; and each AA1 and AA2 are independently a sidechain of an amino acid. In one embodiment each m is independently 1, 2, 3, 4, 5, or 6; each n1 is independently 1, 2, 3, 4, 5, 6, 7 or 8; each p1 is independently 1, 2, 3, 4, 5, 6, 7 or 8; each t is independently 1, 2, 3, 4, 5, 6, 7 or 8; each n2 is independently 1, 2, 3, 4, 5, 6, 7 or 8; each p2 is independently 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, or 12; each q2 is independently 1, 2, 3, 4, 5, or 6; each s is independently 1, 2, 3, 4, 5, or 6; and each AA1 and AA2 are independently a sidechain of an amino acid. In one embodiment the side chain of an amino acid is a side chain of a natural amino acid or citrulline. In one embodiment each sidechain of an amino acid (AA1 and AA2) is independently H, methyl, isopropyl, or -(CH2)3-NH-C(=O)-NH2. In one embodiment each X is independently selected from an ester, activated ester, haloacetamide, halo, and disulfanylheteroaryl. In one embodiment each X is selected from phenoxycarbonyl, 2,5- dioxopyrollidinyloxycarbonyl, disulfanylpyridinyl, and bromoacetyl, wherein the phenoxycarbonyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) halo, nitro, or (C1-C6)alkyl. In one embodiment each X is selected from 2,3,5,6,-tetrafluorophenoxycarbonyl, 2,5- dioxopyrollidinyloxycarbonyl, disulfanylpyridinyl, and bromoacetyl. In one embodiment each X is selected from 2,3,5,6,-tetrafluorophenoxycarbonyl and bromoacetyl, One embodiment provides a compound selected from the group consisting of , , or a salt thereof. One embodiment provides a compound selected from the group consisting of and or a salt thereof. One embodiment provides a compound selected from the group consisting of , , or a salt thereof (e.g., a pharmaceutically acceptable salt thereof). In one embodiment p is 1, 2, 3, 4, or 5. In one embodiment p is 1, 2, 3, 4, 5, 6, 7, or 8. In one embodiment p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In one embodiment provides a mixture of the antibody-drug conjugate compounds of formula I, wherein the average drug loading per antibody in the mixture of antibody-drug conjugate compounds is about 1 to about 5. Provided below are certain non-limiting embodiments of the invention. It is to be understood that two or more embodiments may be combined. One embodiment provides a compound selected from the group consisting of: wherein: P is an amine nitrogen protecting group; each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl; and R2is a (C1-C6)alkyl; or a salt thereof. One embodiment provides a compound selected from the group consisting of:

[0003] or a salt thereof. One embodiment provides a compound selected from the group consisting of: or a salt thereof. One embodiment provides a compound selected from the group consisting of: or a salt thereof. One embodiment provides a compound selected from the group consisting of: or a salt thereof. One embodiment provides a method for preparing a compound of formula 8*: or a salt thereof, comprising converting a corresponding compound of formula 7*: 7* or a salt thereof, to the compound of formula 8 or a salt thereof. One embodiment provides a method for preparing a compound of formula 7*: 7* or a salt thereof, comprising converting a corresponding compound of formula 6a*: 6a* or a salt thereof, to the compound of formula 7* or a salt thereof, wherein R2is a (C1-C6)alkyl. One embodiment provides a method, wheren the compound of formula 7* or a salt thereof is prepared, comprising converting a corresponding compound of formula 6a*: 6a* or a salt thereof, to the compound of formula 7* or a salt thereof, wherein R2is a (C1-C6)alkyl. In one embodiment the compound of formula 6a* is a compound of formula 6*: or a salt thereof. One embodiment provides a method for preparing a compound of formula 6a*: or a salt thereof, comprising converting a corresponding compound of formula 5a*: 5a* or a salt thereof, to the compound of formula 6a* or a salt thereof, wherein: each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl; and R2is a (C1-C6)alkyl. One embodiment provides a method, wherein the compound of formula 6a* or a salt thereof is prepared, comprising converting a corresponding compound of formula 5a*: 5a* or a salt thereof, to the compound of formula 6a* or a salt thereof, wherein each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1-C6)alkyl. In one embodiment the compound of formula 6a* is a compound of formula 6*: 6* or a salt thereof. In one embodiment the the compound of formula 5a* is a compound of formula 5*: 5* or a salt thereof. One embodiment provides a method, wherin the compound of formula 6a* is prepared, comprising reacting the compound of formula 5a* or a salt thereof, with a compound of formula Ba: or a salt thereof, to provide the compound of formula 6a*, wherein R2is a (C1-C6)alkyl. In one embodiment the compound of formula Ba* is a compound of formula B*: or a salt thereof. One embodiment provides a method, wherin the compound of formula 6* is prepared, comprising reacting the compound of formula 5a* or a salt thereof, with a compound of formula B*: or a salt thereof, to provide the compound of formula 6*. One embodiment provides a method for preparing a compound of formula 5a*: 5a* or a salt thereof, comprising converting a corresponding compound of formula 4a*: or a salt thereof, to the compound of formula 5a or a salt thereof, wherein each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1-C6)alkyl. One embodiment provides a method, wheren the compound of formula 5a* or a salt thereof is prepared, comprising converting a corresponding compuonf of formula 4a*: or a salt thereof, to the compound of formula 5a* or a salt thereof. In one embodiment the compound of formula 5a* is a compound of formula 5*: or a salt thereof, and the compound of formula 4a* is a compound of formula 4*: 4* or a salt thereof. One embodiment provides a method, wherein the compound of formula 5a* is prepared, comprising reacting the compound of formula 4a* or salt thereof with a compound of formula A* or salt thereof, to provide the compound of formula 5a* or a salt thereof. One embodiment provides a method for preparing a compound of formula 5*, comprising reacting the compound of formula 4* or salt thereof, with a compound of formula A*: A* or salt thereof, to provide the compound of formula 5* or a salt thereof. One embodiment provides a method for preparing a compound of formula 4a*: or a salt thereof, comprising converting a corresponding compound of formula 3a*: or a salt thereof, to the compound of formula 4a* or a salt thereof, wherein: P is an amine nitrogen protecting group; and each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl. One embodiment provides a method, wherein the compound of formula 4a* or a salt thereof is prepared, comprising converting a corresponding compound of formula 3a*: or a salt thereof, to the compound of formula 4a* or a salt thereof, wherein each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1-C6)alkyl. In one embodiment the compound of formula 4a* or a salt thereof is a compound of formula 4*: 4* or a salt thereof, and the compound of formula 3a* or a salt thereof is a compound of formula 3*: 3* or a salt thereof. One embodiment provides a method for preparing a compound of formula 3a*: 3a* or a salt thereof, comprising converting a corresponding compound of formula 2a*: 2a* or a salt thereof, to the compound of formula 3a* or a salt thereof, wherein: P is an amine nitrogen protecting group; and each R1is independently a (C1-C6)alkyl or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl. One embodiment provides a method, wheren the compound of formula 3a* or a salt thereof is prepared, comprising converting a corresponding compound of formula 2a*: 2a* or a salt thereof, to the compound of formula 3a* or a salt thereof, wherein P is an amine nitrogen protecting group. In one embodiment the compound of formula 3a* or a salt thereof, is a compound of formula 3*: or a salt thereof, and the compound of formula 2a* is a compound of formula 2: or a salt thereof. It is to be understood that 2 or more of the above described embodiments may be combined. A compound described herein or a salt thereof can be prepared as illustrated in Scheme 1 or Scheme 2. Scheme 1

[0004] Scheme 2 PHARMACEUTICAL FORMULATIONS Pharmaceutical formulations of therapeutic antibody-drug conjugates (ADC) of the invention are typically prepared for parenteral administration, i.e. bolus, intravenous, intratumor injection with a pharmaceutically acceptable parenteral vehicle and in a unit dosage injectable form. An antibody-drug conjugate (ADC) having the desired degree of purity is optionally mixed with pharmaceutically acceptable diluents, carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences (1980) 16th edition, Osol, A. Ed.), in the form of a lyophilized formulation or an aqueous solution. ANTIBODY-DRUG CONJUGATE METHODS OF TREATMENT It is contemplated that the antibody-drug conjugates (ADC) of the present invention may be used to treat various diseases or disorders, e.g. characterized by the overexpression of a tumor antigen. Exemplary conditions or hyperproliferative disorders include benign or malignant solid tumors and hematological disorders such as leukemia and lymphoid malignancies. The antibody-drug conjugates (ADC) of the invention may be administered by any route appropriate to the condition to be treated. The ADC will typically be administered parenterally, i.e. infusion, subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural. Generally, the disease or disorder to be treated is a hyperproliferative disease such as cancer. Examples of cancer to be treated herein include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia or lymphoid malignancies. More particular examples of such cancers include squamous cell cancer (e.g. epithelial squamous cell cancer), lung cancer including small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung and squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastric or stomach cancer including gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, rectal cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney or renal cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, as well as head and neck cancer. Certain embodiments of the invention provide a method for treating cancer in a patient in need thereof, comprising administering a therapeutically effective amount of an antibody described herein (e.g., anti-Trop2 antibody), or the pharmaceutical composition comprising the antibody, to the patient in need thereof. In certain embodiments, the antibody is conjugated to payload drug. In certain embodiments, the antibody is a naked antibody or fragment thereof (that is not conjugated to payload drug). In certain embodiments, the pharmaceutical composition comprises the naked antibody and does not comprise antibody conjugated with payload drug. In certain embodiments, the antibody may modulate (e.g., reduce) the target antigen (e.g., Trop2) level on the cell membrane surface, for example, the antibody may induce internalization of the target antigen. In certain embodiments, the antibody may modulate (e.g., reduce) the target antigen mediated signaling, for example, the antibody may block the binding between the target antigen (e.g., Trop2) and its endogenous ligand(s). In certain embodiments, the antibody may modulate (e.g., enhance) ADCC and / or CDC activity towards the cell expressing the target antigen. Certain embodiments of the invention provide a method for treating cancer in a patient in need thereof, comprising administering a therapeutically effective amount of an antibody drug conjugate compound described herein, or the pharmaceutical composition comprising the ADC, to the patient in need thereof. In certain embodiments, the cancer is selected from lung cancer (e.g., non-small cell lung cancer), pancreatic cancer, esophageal cancer, gastric cancer, bladder cancer, ovarian cancer, breast cancer, uterine cancer, and head and neck cancer. In certain embodiments, the cancer is selected from lung cancer (e.g., non-small cell lung cancer, lung adenocarcinoma, and large cell lung carcinoma), pancreatic cancer, esophageal cancer, gastric cancer, bladder cancer, ovarian cancer, breast cancer, and uterine cancer. In certain embodiments, the patient has Trop2 positive tumor cells. In certain embodiments, the patient has tumor cells comprising one or more mutation that is a loss-of-function mutation in a tumor suppressor gene, and / or a gain-of-function mutation in an oncogenic driver gene and / or amplification of an oncogenic driver gene. In certain embodiments, the patient has tumor cell(s) that comprises one or more genetic aberration or mutation as listed in Table B3. In certain embodiments, the patient has tumor cell(s) that comprises one or more mutation in a gene selected from the group consisting of KRAS, BRAF, EGFR, ERBB2, ERBB3, APC, CNGA2, ARID1A, SLC34A2, ROS1, FGFR3, TACC3, BAIAP2L1, PIK3CA, PIK3R1, BRCA2, PTEN, STK11, CDKN2A, SMAD4, TP53, UGT2B17, SMARCA2, and SMARCA4. In certain embodiments, the patient has tumor cell(s) that comprises one or more mutation in a gene selected from the group consisting of ATM, NF1, AKT1 / 2, CLPTM1L, and PVT1, NSD1 and MRE11A. In certain embodiments, the one or more mutation comprises a point mutation. In certain embodiments, the one or more mutation comprises a mutation selected from the group consisting of KRas G12V, BRAF G466V, EGFR L861Q, PIK3CA E545K, APC R1450*, PIK3R1 R386fs, PIK3R1 R639ter, TP53 V218, ARID1A L649fs / R693ter and SMARCA4 G1162C. In certain embodiments, the one or more mutation comprises a gain-of-function mutation. In certain embodiments, the patient has tumor cell that comprises one or more mutation in a gene selected from the group consisting of KRAS, BRAF, EGFR, SLC34A2, ROS1, FGFR3, TACC3, BAIAP2L1, PIK3CA, PIK3R1, and BRCA2. In certain embodiments, the one or more mutation comprises a loss-of-function mutation. In certain embodiments, the subject (e.g., patient) has tumor cell that comprises one or more mutation in a gene selected from the group consisting of PTEN, STK11, CDKN2A, SMAD4, and TP53. In certain embodiments, the one or more mutation comprises fusion mutation of two genes. In certain embodiments, the one or more mutation comprise fusion mutation selected from the group consisting of SLC34A2-ROS1, FGFR3-TACC3, and FGFR3-BAIAP2L1. In certain embodiments, the one or more mutation comprises a BRCA-deficient mutation, FGFR3 gain-of-function mutation, TP53 loss-of-function mutation, or SMARCA4 loss-of-function mutation. In certain embodiments, the one or more mutation is copy number variations (CNV). In certain embodiments, one or more copy number variations (CNV) comprises a partial or total loss of PTEN, STK11, CDKN2A, CNGA2, SMAD4, UGT2B17; or gain / amplification of ERBB2, ERBB3, PIK3CA. In certain embodiments, the patient has HPV positive tumor cells. In certain embodiments, the patient has HPV39 positive tumor cells. In certain embodiments, the patient is unresponsive to standard-of-care (SOC) therapy. The term “standard-of-care” or “SOC” refers to treatment that is accepted by medical experts as a proper treatment for a certain type of disease (e.g., cancer) and that is widely used by medical experts in the relevant field as likely best practice, and / or standard therapy. In certain embodiments, the patient (e.g., having tumor cells) unresponsive to standard-of-care may show resistance to MEK or BET inhibitor therapy (e.g., in Lung adenocarcinoma), anti-EGFR therapy (e.g., in NSCLC), or multi-kinase inhibitor therapies, such as Sorafenib or AZ628 inhibitors (e.g., in Gastric cancer). For the prevention or treatment of disease, the appropriate dosage of an ADC will depend on the type of disease to be treated, as defined above, the severity and course of the disease, whether the molecule is administered for preventive or therapeutic purposes, previous therapy, the patient's clinical history and response to the antibody, and the discretion of the attending physician. The molecule is suitably administered to the patient at one time or over a series of treatments. Depending on the type and severity of the disease, about 1 µg / kg to 15 mg / kg (e.g.0.1-20 mg / kg) of molecule is an initial candidate dosage for administration to the patient, whether, for example, by one or more separate administrations, or by continuous infusion. A typical daily dosage might range from about 1 µg / kg to 100 mg / kg or more, depending on the factors mentioned above. An exemplary dosage of ADC to be administered to a patient is in the range of about 0.1 to about 10 mg / kg of patient weight. Antibodies or immunoconjugates of the invention can be used either alone or in combination with other agents in a therapy. For instance, an antibody or immunoconjugate of the invention may be co-administered with at least one additional therapeutic agent. Such combination therapies noted above encompass combined administration (where two or more therapeutic agents are included in the same or separate formulations), and separate administration, in which case, administration of the antibody or immunoconjugate of the invention can occur prior to, simultaneously, and / or following, administration of the additional therapeutic agent and / or adjuvant. Antibodies or immunoconjugates of the invention can also be used in combination with radiation therapy. An antibody or immunoconjugate of the invention (and any additional therapeutic agent) can be administered by any suitable means, including parenteral, intrapulmonary, and intranasal, and, if desired for local treatment, intralesional administration. Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. Dosing can be by any suitable route, e.g. by injections, such as intravenous or subcutaneous injections, depending in part on whether the administration is brief or chronic. Various dosing schedules including but not limited to single or multiple administrations over various time-points, bolus administration, and pulse infusion are contemplated herein. Antibodies or immunoconjugates of the invention would be formulated, dosed, and administered in a fashion consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the scheduling of administration, and other factors known to medical practitioners. The antibody or immunoconjugate need not be, but is optionally formulated with one or more agents currently used to prevent or treat the disorder in question. The effective amount of such other agents depends on the amount of antibody or immunoconjugate present in the formulation, the type of disorder or treatment, and other factors discussed above. These are generally used in the same dosages and with administration routes as described herein, or about from 1 to 99% of the dosages described herein, or in any dosage and by any route that is empirically / clinically determined to be appropriate. For the prevention or treatment of disease, the appropriate dosage of an antibody or immunoconjugate of the invention (when used alone or in combination with one or more other additional therapeutic agents) will depend on the type of disease to be treated, the type of antibody or immunoconjugate, the severity and course of the disease, whether the antibody or immunoconjugate is administered for preventive or therapeutic purposes, previous therapy, the patient's clinical history and response to the antibody or immunoconjugate, and the discretion of the attending physician. The antibody or immunoconjugate is suitably administered to the patient at one time or over a series of treatments. Depending on the type and severity of the disease, about 1 µg / kg to 15 mg / kg (e.g.0.1mg / kg-10mg / kg) of antibody or immunoconjugate can be an initial candidate dosage for administration to the patient, whether, for example, by one or more separate administrations, or by continuous infusion. One typical daily dosage might range from about 1 µg / kg to 100 mg / kg or more, depending on the factors mentioned above. For repeated administrations over several days or longer, depending on the condition, the treatment would generally be sustained until a desired suppression of disease symptoms occurs. One exemplary dosage of the antibody or immunoconjugate would be in the range from about 0.05 mg / kg to about 10 mg / kg. Thus, one or more doses of about 0.5 mg / kg, 2.0 mg / kg, 4.0 mg / kg or 10 mg / kg (or any combination thereof) may be administered to the patient. Such doses may be administered intermittently, e.g. every week or every three weeks (e.g. such that the patient receives from about two to about twenty, or e.g. about six doses of the antibody). An initial higher loading dose, followed by one or more lower doses may be administered. However, other dosage regimens may be useful. The progress of this therapy is easily monitored by conventional techniques and assays. ARTICLES OF MANUFACTURE In another embodiment of the invention, an article of manufacture, or “kit”, containing materials useful for the treatment of the disorders described above is provided. The article of manufacture comprises a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, blister pack, etc. The containers may be formed from a variety of materials such as glass or plastic. The container holds an antibody-drug conjugate (ADC) composition which is effective for treating the condition and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). At least one active agent in the composition is an ADC. The label or package insert indicates that the composition is used for treating the condition of choice, such as cancer. Alternatively, or additionally, the article of manufacture may further comprise a second (or third) container comprising a pharmaceutically-acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution and dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes. EXAMPLES Certain exemplary embodiments of anti-Trop2 antibody drug conjugate invention described herein may be referred to as Trop2 PH1 ADCs or PH Trop2 ADCs, wherein a new payload (e.g., PH1 or compound 3A) is conjugated to a Peak Trop2 antibody, also referred to as PH antibody (e.g., M2.8 mAb). For example, certain embodiments of an exemplary M2.8 mAb conjugated with PH1 payload is referred to as M2.8 PH1 in Example 4 or M2.8 L22 ADCs in Example 12. The Thailanstatin (PH1) payload is also referred to as PH1-3, or A13d2Th. Certain exemplary embodiments of anti-Trop2 antibody drug conjugate invention described herein may comprise a new payload (e.g., Thailanstatin (PH1)) described herein that is conjugated to a known antibody. The known antibody may be hRS7 (also referred to as Sacituzumab, namely the antibody unit of IMMU-132). The known antibody may be TINA (also referred to as DS1062a or Datopotamab, namely the antibody unit of DS-1062). The known antibody may be 2G10 (namely the antibody unit of LCB84). The known antibody may be T6-16. Example 1. Trop2 ADC linker screening. The efficacy of various linker-toxins as ADC were evaluated in this Example. The antibody is the anti-TROP2 hRS7 (Sacituzumab, the antibody of IMMU-132) and the toxin being evaluated is Thailanstatin (PH1, also referred to as PH1-3, or A13d2Th). L2 (NHS) and L22 (TFP) are conjugated via noncleavable lysine and may release the same catabolite intracellularly after the ADC is digested within the cell. L92 (Val-Ala TFP) is conjugated via a cleavable lysine and may release a different catabolite. L18 is conjugated via non-cleavable cysteine and may release a different catabolite from L2 / 22. This Example evaluates the efficacy of linker toxin combinations on N87 gastric carcinoma that expresses high levels of Trop2 and Her2 and is therefore susceptible to Trop2- ADC or Her2-ADC inhibition. Athymic mice bearing pre-implanted N87 tumors were i.v. treated with 3 mg / kg of various linker toxin ADCs and efficacy read as a function of tumor volume over time. DAR 4 / 8 versions of Trop2 PH1 ADC were included in the experiment. At 3 mg / kg, anti-Trop2 ADCs were the most efficacious when conjugated on random lysines with non-cleavable linkers L-2 (77% TGI) and L-22 (82% TGI). The slightly higher activity of L-22 (DAR 4.5) linker over L-2 (DAR 3.65) Trop2 PH1 ADC may be due to higher DAR during conjugation, see Figure 1. Using a L-2 linker, Trop2 PH1 ADCs were more efficacious as a DAR8 vs a DAR4 species (88% vs 77% TGI). While the DAR8 ADC may be more efficacious than the DAR4 species in such model of this Example, one needs also balance the stability and toxicity of the former for therapeutic index considerations. At the same dose, the activity of above anti-Trop2 ADCs were comparable to Kadcyla, which targets Her2-expressing cells and is an approved drug for therapy of Gastric Carcinoma. In comparison, anti-Trop2 ADCs made by coupling the same toxin to random lysines using a cleavable linker L-92 or to cysteine using a non-cleavable linker L-18 showed lower efficacy of about 68% and 65% TGI, respectively. Overall, in this Example, the lysine conjugates with non-cleavable linker have highest potency. Example 2. Antibody binding profile and binding affinity for Trop2 This Example relates to the characterization and analysis of anti-Trop2 antibodies as naked mAbs. In particular, binding affinity / binding profile were also compared with mAbs TINA and hRS7, respectively. Binding affinity and binding profiles were determined by Biolayer Interferometry (BLI). Binding assays were performed on Octet Red instrument at 25°C. Antibodies were loaded onto anti-human IgG Fc capture biosensors for 300 seconds. Ligand-loaded sensors were dipped into a 3-fold series dilution (starting at 300 nM in 0.1% BSA, 1X PBS, 0.02% Tween20, and 0.05% NaN3) of Trop2 for 200 seconds followed by dissociation for 400 seconds. Kinetic constants were calculated using a monovalent (1:1) binding model. PH antibodies (e.g., M2.1, M2.2., M2.8) and mAbs TINA and hRS7 were produced from CHO cells for comparison in binding affinity towards Trop2. Binding analysis of select PH antibodies and other antibodies show varying profiles on the Octet sensograms (Figure 2). While the antibodies all had similar kon values, the dissociation values were noticeably different. Whereas the TINA antibody dissociated rapidly, the hRS7 antibody had near stagnant dissociation. In comparison, PH antibodies showed a moderate dissociation in between TINA and hRS7 antibodies. Upon calculated analysis of binding affinity, the hRS7 antibody and select Peak Bio antibodies (e.g., M2.8) had sub-10 nM binding affinity (Table A1). The TINA antibody bound less tightly at 24.61 nM (Table A1). Table A1 Binding affinity of mAb to antigen calculated with a monovalent model (1:1). While all the M2 antibodies had similar binding behavior, M2.8 ultimately had a slightly higher binding affinity. Example 3. PH antibodies (e.g., M2.1, M2.8) bind human and cynomolgus monkey Trop2 To evaluate the binding of PH antibodies (e.g., M2.1, M2.8) mAb to human, cyno, and mouse Trop2, Chinese Hamster Ovary (CHO) cells were transfected with Trop2 cDNA constructs to transiently overexpress human, cyno, or mouse Trop2. Antibodies were incubated with Chinese Hamster Ovary (CHO) cells that transiently overexpress Trop2 to test antibodies’ binding profile with human, cynomolgus monkey, or mouse Trop2 using flow cytometry. PH antibodies (e.g., M2.1) bind human and cynomolgus monkey, but not rodent Trop2 (Fig.3A). hRS7 (IMMU-132) mAb binds human and cynomolgus monkey Trop2 (Fig.3B). REA916 antibody binds to an epitope common to all above species and was used as a positive control (Fig.3C). TINA (DS-1062) mAb binds human and cynomolgus monkey Trop2 (Fig.3D). Example 4. Efficient conjugation of linker toxin to Trop2 mAb and characterization of ADCs (DAR2 or DAR4 versions) Conjugation of PH1 to PH antibody (e.g., M2.8) M2.8 antibody was buffer exchanged to 50 mM borate / 50 mM NaCl pH 8.5 buffer (BB) in Amicon concentrators (30 kDa, regenerated cellulose). Antibody in BB was carefully adjusted to 10 mg / mL with additional BB then cooled on ice until 4°C. PH1L2 was added at varying molar excesses of 2.2, 2.6, 4.2, or 4.8 to the antibody and quickly mixed in. The reaction was kept overnight at 4°C to ensure the conjugation reaction went to completion. Conjugated M2.8 PH1 was harvested, and buffer exchanged into phosphate buffered saline (PBS) with the above-mentioned method and finally filtered through a 0.22 μm PES filter. DAR analysis of conjugates revealed molar excesses of 2.2, 2.6, 4.2, and 4.8 gave rise to experimental DARs of 1.6, 2.0, 3.3 and 3.6, respectively. The successful molar excesses of experimental DARs in smaller batch conjugations were used to drive conjugations for larger batches. Plus / minus 0.5 of the target DAR was considered acceptable. For example, an experimental DAR of 3.5-4.5 was released for testing as a DAR4 ADC. At 10-25mg scale, molar excesses of 5, 6 and 8 PH1 were used to drive conjugations in order to achieve a DAR of 4. High-performance liquid chromatography ADCs diluted in PBS were run on a size exclusion column (SEC) with the Agilent 1100 HPLC machine. Readouts taken at 280 nm with the diode-array detection were used to identify the protein and if there are aggregates. Similarly, ADCs were run on a hydrophobic interaction column (HIC) HPLC. Mass spectrometry ADCs were characterized with electrospray ionization liquid chromatography mass spectrometry. Results of M2.8 PH1 (DAR2 or DAR4 versions) characterization Upon conjugation of the M2.8 antibody with PH1 payload, M2.8 PH1 was characterized on both HIC (Figure 6, A and D) and by SEC (Figure 6, B and E). Figure 6A and 6D (DAR2 or DAR4 versions) show the analytes eluting out around the 2.2-minute time point with subsequently multiple peaks afterwards forming a single large peak, indicating a heterogenous ADC population conjugated at different lysines with an increasing number of PH1 payloads. Given the closeness of various populations of PH1 on M2.8, mass spectrometry (MS) was used to clarify the exact average drug-to-antibody ratio (DAR) of M2.8 PH1 population. ESI-MS provided the breakdown in distribution of each DAR population (Figure 6C or Figure 6F, for DAR2 or DAR4 versions), where a range from 0 to 4 DAR (DAR 2) or 1 to 7 DAR (DAR 4) was observed. The average DAR of each population of DAR2 version or DAR4 version is about 1.7 or 3.6, respectively. Thus, M2.8 PH1 ADCs can be controlled to yield minimal aggregation (<1.5% as measured by SEC-HPLC) and reproducibly yield a DAR of 1.5-2 or 3.5-4.0 (by LC-MS). The conjugation efficiency of M2.8 with PH1 can be verified reliably by ESI-MS. Example 5. Cellular internalization of Trop2 mABs and ADCs Internalization assay was performed with Trop2 mAbs: hRS7, M2.1, M2.3, T6-16, TINA. Control Ab used was HuLys 11 targeting chicken lysozyme. hRS7 and TINA appear to internalize more rapidly, but T6-16 shows the highest internalization percentage (Figure 7). M2.1 and M2.8 ADCs showed similar internalization (accumulation) rates in cells (Figure 8). Method Percent internalization was calculated based on fraction internalized at time x minus fraction internalized at start, and then multiplied by 100 using formula:([V(tx) / M(tx)] - [V(t0) / M(t0)]) * 100 , where V and M are average Geometric Mean Fluorescence Intensity signals (GMFI) of Alexa 488- conjugated mAbs or ADCs bound to antigen-expressing cells; and quenching photo-bleaches the fluorescent-labeled antigen-antibody complexes on the cell surface leaving signal available from only the internalized complexes. V(t0) and M(t0) represent the amount of pulse-labeled receptor-mAb complexes at start time t0, at the beginning of the chase, that were quenched and unquenched, respectively. V(tx) and M(tx) represent corresponding quenched and unquenched fluorescence values from mAb-labeled receptors initiated in parallel at time t0, but quenched after a period x, tx, respectively. The GMFIs of V(tx) and M(tx) represent amounts of quenched and unquenched complexes at the end of the chase periods. Samples were quenched at time intervals of x=0.5, 3 and 6 hours Cells were trypsinized and plated the night before (50-100k cells / well). Plates, media, and 1X PBS were pre-chilled on ice for 15 mins. Cells were washed 1x with cold PBS followed by aspiration of PBS. Abs were diluted to 1.5 ug / ml in pre-chilled indicator free media. Diluted primary Abs were transferred to wells at 200 ul / well. Cells were incubated for 30 min on ice. Cells were washed 1x with cold PBS followed by aspiration of PBS (step repeated). Quenching antibody was diluted as described above in pre-chilled indicator free media. For T0 plate, quenching antibody was transferred at 200 ul / well to time point 0 plate. Cells were incubated for 30 min on ice. Cells were washed 1x with cold PBS followed by aspiration of PBS. Cells were trypsinized and transferred to V-bottom polystyrene plate. After spinning 5 min at 1200 rpm, buffer was aspirated, and cell pellet was retained. Cells were washed 1x with cold PBS followed by spinning 5 min at 1200 rpm. Cell pellet was re- suspended in 200 ul indicator free media. Cell samples were read using the Guava Easycyte Plus HT flow cytometer and data were analyzed using the Guava Cytosoft software suite. For all other time point plates, 200 uL of prewarmed media was added to wells of all remaining plates, which were placed in 37°C incubator for 0.5hr, 3hrs or 6hrs. Plate was removed from incubator and excess of prechilled PBS was added. Plate was placed on ice for 15 mins. Buffer was aspirated. Quenching antibody was transferred to each plate at 200 ul / well. Plate was incubated on ice for 30 min. Cells were washed 1x with cold PBS and then buffer was aspirated. Cells were trypsinized and transferred to V-bottom polystyrene plate. After spinning 5 min at 1200 rpm, buffer was aspirated, and cell pellet was retained. Cells were washed 1x with cold PBS followed by spinning 5 min at 1200 rpm. Cell pellet was re- suspended in 200 ul indicator free media. Cell samples were read using the Guava Easycyte Plus HT flow cytometer and data were analyzed using the Guava Cytosoft software suite. Example 6. Payload superiority of PH1 (when conjugated on IMMU-132 antibody hRS7) over SN-38 on IMMU-132 antibody To determine whether PH Trop2 ADCs with Thailanstatin payloads have comparable (or better) activity than best-in-class anti-Trop2 ADC, IMMU-132 (SN-38 conjugated on hRS7 at DAR8), using the same hRS7 antibody but different payloads (PH1 vs SN-38), the tumor inhibition efficacy of IMMU-132 at its efficacious dose of 10mpk QW x2 was compared with the efficacy of PH1 payload ADC at lower dose (1mpk QW x3 or 3mpk QW x2) and lower DAR (DAR4). The number of mice with regressed tumors within the cohort is represented as a fraction of the total. Results PH1 demonstrated significant TGI as payload on hRS7 mAb. The hRS7 mAb, that is part of first-in-class IMMU-132 (Sacituzumab Govitecan), demonstrated significantly better anti-tumor efficacy with a PH1 payload at DAR4 than the clinically approved SN38 conjugate at DAR8 (Figure 9), suggesting that PH1 payload ADC may provide superior efficacy at lower dose and / or lower DAR as compared to SN-38. Conclusion Using the same hRS7 mAb, ADC conjugated with PH1 payload demonstrated significantly better activity than SN38-containing IMMU-132, even though the IMMU-132 was conjugated to SN38 at DAR8 and PH1 was conjugated at DAR 4. When administered at 3mpk QWx2, ADC with PH1 payload exhibited greater TGI than IMMU-132 at 10mpk QWx2. ADC with PH1 payload also performed better in suboptimal dose of 1mpk as compared to IMMU-132 at 1mpk. Method N87 gastric carcinoma cells express high levels of endogenous Trop2 protein. IMMU- 132 is currently the first-in-class (FIC) Trop2 ADC using the mAB hRS7 conjugated to the irinotecan metabolite payload SN-38 at a drug-antibody ratio (DAR) of 8. It is a standard-of- care (SOC) for treatment of triple negative breast cancer (TNBC), and is currently being tested in the clinic for activity against gastric cancer that expresses elevated levels of Trop2. In pre-clinical gastric cancer model N87, 10mpk QWx2 was established as the efficacious dose of IMMU-132. ADCs were tested for the treatment of subcutaneous NCI-N87 gastric Cancer Xenograft Model in female BALB / c nude Mice. Cell Culture The NCI-N87 tumor cell line was maintained in vitro in RPMI1640 medium supplemented with 10% fetal bovine serum at 37 ºC in an atmosphere of 5% CO2 in air. The tumor cells were routinely sub-cultured twice weekly by trypsin-EDTA treatment. The cells growing in an exponential growth phase were harvested and counted for tumor inoculation. Tumor Inoculation Each mouse was inoculated subcutaneously in the right flank region with tumor cells (1*107) in 0.1 ml of PBS mixed with Matrigel (1:1) for tumor development. Randomization The randomization was started when the mean tumor size reached approximately 195.81 mm3. All animals were randomly allocated to study groups. Randomization was performed based on “Matched distribution” method (StudyDirectorTM software, version 3.1.399.19). Observation and Data Collection After tumor cells inoculation, the animals were checked daily for morbidity and mortality. During routine monitoring, the animals were checked for any effects of tumor growth and treatments on behavior such as mobility, food and water consumption, body weight gain / loss (Body weights were measured twice per week after randomization), eye / hair matting and any other abnormalities. Mortality and observed clinical signs were recorded for individual animals in detail. Tumor volumes were measured twice per week after randomization in two dimensions using a caliper, and the volume was expressed in mm3using the formula: V = (L x W x W) / 2, where V is tumor volume, L is tumor length (the longest tumor dimension) and W is tumor width (the longest tumor dimension perpendicular to L). Dosing as well as tumor and body weight measurements were conducted in a Laminar Flow Cabinet. The body weights and tumor volumes were measured by using StudyDirectorTM software (version 3.1.399.19). ADC administration The treatment was initiated on the same day of randomization (day 7) per study design. Tumor growth inhibition (TGI): TGI% is an indication of antitumor activity, and expressed as: TGI (%) =100 x (1-T / C). T and C are the mean tumor volume (or weight) of the treated and control groups, respectively, on a given day. Statistical analysis of the difference in mean tumor volume among the groups was conducted using the methods below: Use the data collected on the last observation day for every single group in despite of diverse individual termination date. To compare tumor volumes of different groups at a pre-specified day, Bartlett's test was first used to check the assumption of homogeneity of variance across all groups. When the p-value of Bartlett's test was >= 0.05, a one-way ANOVA was performed to test overall equality of means across all groups. If the p-value of the one-way ANOVA was < 0.05, a post hoc testing was performed by running Tukey's HSD (honest significant difference) tests for all pairwise comparisons, and Dunnett's tests for comparing each treatment group with the vehicle group. When the p-value of Bartlett's test was <0.05, a Kruskal-Wallis test was performed to test overall equality of medians among all groups. If the p-value the Kruskal- Wallis test was <0.05, a post hoc testing was performed by running Conover's non-parametric test for all pairwise comparisons or for comparing each treatment group with the vehicle group, both with single-step p-value adjustment. In addition, pairwise comparisons were performed without multiple comparison correction and nominal / uncorrected p-values were reported directly from Welch's t-test or Mann-Whitney U test. Specifically, Bartlett's test was first used to check the assumption of homogeneity of variance for a pair of groups. When the p-value of Bartlett's test was ≥0.05, a Welch's t-test was performed, otherwise a Mann-Whitney U test was performed to obtain nominal p-values. All statistical analyses had been done in R-a language and environment for statistical computing and graphics (version 3.3.1). All tests were two-sided unless otherwise specified, and p-values of <0.05 were regarded as statistically significant. Example 7. superiority of Trop-2 PH1 ADC (M2.1) over IMMU-132 To determine whether PH Trop2 ADC (M2.1 mAb) with Thailanstatin (PH1) payload have comparable (or better) activity than best-in-class anti-Trop2 ADC, IMMU-132, the tumor inhibition efficacy of IMMU-132 at its efficacious dose of 10mpk QW x2 was compared with the efficacy of PH ADC of M2.1 mAb conjugated with PH1 payload at lower dose (3mpk QW x2) and lower DAR (DAR2 or DAR4). Suboptimal dose at 1mpk QW x3 comparison was also investigated. The number of mice with regressed tumors within the cohort is represented as a fraction of the total. Method N87 gastric carcinoma cells express high levels of endogenous Trop2 protein. IMMU-132 is currently the best-in-class (BIC) Trop2 ADC using the mAB hRS7 conjugated to the irinotecan metabolite payload SN-38 at a drug-antibody ratio (DAR) of 8. It is a standard-of- care (SOC) for treatment of triple negative breast cancer (TNBC),and is currently being tested in the clinic for activity against gastric cancer that expresses elevated levels of Trop2. In pre-clinical gastric cancer model N87, 10mpk QWx2 was established as the efficacious dose of IMMU-132. Results When durability of the TGI was assessed, PH Trop2 ADC (mAb M2.1 conjugated with PH1 payload) performed significantly better than IMMU-132 at preventing tumor growth. The results support the use of M2.1 PH Trop2 mAb Thailanstatin ADC at DAR2 or DAR4 for further assessment as a candidate. PH1 payload demonstrated significantly improved efficacy on PH mAb (M2.1) as compared to the SN38-payload containing IMMU- 132 (Figure 10). Conclusion PH Trop2 ADCs conjugated with PH1 payload demonstrated significantly better activity than SN38-containing IMMU-132, even though IMMU-132 was conjugated at DAR8 while PH Trop2 ADCs were conjugated at DARs 4 and 2. When administered at 3mpk QWx2, PH Trop2 ADCs exhibited greater TGIs than IMMU-132 at 10mpk QWx2. When PH Trop2 ADCs conjugated with PH1 payload were compared at 1mpk QWx3 dose in a dose-matched suboptimal setting, efficacy of PH1 payload conjugated Trop2 ADCs was higher than IMMU-132, which is largely inactive at this dose, whereas PH1-Trop2 ADCs (M2.1 conjugated with PH1 at DAR2 or DAR4) have about 45-70% TGI. At suboptimal dose, M2.1 ADCs exhibited better efficacy at DAR4 vs DAR2. However, when dosed sufficiently high such as 3mpk QWx2, there was no significant difference in early anti-tumor efficacies or tumor re-growth properties between M2.1 DAR4 vs DAR2 ADCs. Example 8. Trop2 ADCs with PH1 payload regress tumors The same model was used as described in Examples 6-7. PH mAbs M2.1 and M2.3 were conjugated with PH1 payload at DAR 4 or DAR 2. Anti-Trop2 mAbs T6-16 and hRS7 were conjugated with PH1 payload at DAR4. The number of mice with regressed tumors within the cohort is represented as a fraction of the total. Cohorts with differences in tumor volume significant at p<0.05 with the isotype control anti-RSV PH1 ADC is indicated. All tested Trop2 ADCs with PH1 payload regress individual tumors at 3 mg / kg (Figure 11). All anti-Trop2 ADCs conjugated with PH1 payload demonstrated significantly improved efficacy than SN38-containing IMMU-132, even though IMMU-132 was conjugated at higher DAR 8 and was administered at higher dose of 10mpk. Example 9. Superiority of Trop2 ADCs with PH1 payload over IMMU-132 in suboptimal dose The same model was used as described in Examples 6-7. PH mAbs M2.1 and M2.3 were conjugated with PH1 payload at DAR 4 or DAR 2. Anti-Trop2 mAbs TINA, T6-16 and hRS7 were conjugated with PH1 payload at DAR4. When all Trop2 ADCs with PH1 were compared at 1mpk QWx3 dose in a dose- matched suboptimal setting, efficacy of all PH1 payload conjugated Trop2 ADCs was higher. IMMU-132 at this dose is largely inactive, whereas all PH1-Trop2 ADCs have 45-70% TGI (Figure 12). M2.1 PH1 showed higher TGI than M2.3 PH1. For M2.1 PH1 and M2.3 PH1, DAR4 showed higher TGI than DAR2. Example 10. Trop2 PH1 ADC (M2.8 PH1) is a potent inhibitor of cancers of multiple origins. To evaluate ADC cytotoxicity against multiple cancer indications, an unbiased cytotoxicity screen against a panel of 70 cell lines was performed (Table B1). Trop2 PH1 ADC activity was observed in 30 cell lines representing 9 indications (Table B2). Of these, IC50s of 27 cell lines were lower than 100nM. Single digit nanomolar inhibition was observed in 19 cell lines from 8 indications. A representative list of 25 cell lines with single digit or double digit IC50s is shown in Figure 13 (also see Figures 14A-14C for representative assay using NCI-N87 cells, BxPC3 cells, or RT112 / 84 cells). On the other hand, Trop2 PH1 ADC shows lower off-target toxicity towards Trop2 negative cells as compared to IMMU-132 (see Figures 14D-14F for assay using 786-0 cells, BJ Normal human fibroblast cells, or HS27 Normal human fibroblast cells). Furthermore, Trop2 PH1 ADC efficacy was observed in cancers with oncogenic drivers, such as KRas G12V, BRAF G466V (sorafenib resistance), EGFR L861Q, SLC34A2-ROS1 fusion, FGFR3 GOF or FGFR3 fusions (both FGFR3-TACC3 and FGFR3-BAIAP2L1 fusions), PI- 3K signaling mutations (PIK3CA E545K and PIK3R1 R386fs / R639ter), BRCA2-deficient (familial), and HPV39-positive (Viral) cancers. In addition, Trop2 PH1 ADC efficacy was observed in cancers with loss of function of tumor suppressors, such as PTEN, STK11, CDKN2A, SMAD4, TP53 LOF or TP53 V218 mutation. Trop2 PH1 ADC efficacy was observed in cancers with UGT2B17 loss of function. Trop2 PH1 ADC efficacy was also observed in cancers with compensatory activation due to loss of SMARCA2, SMARCA4 G1162C or LOF. Methods The objective of this Example is to explore the potential effect of ADC on cell viability of 70 cancer cell lines. The 50% inhibitory concentration (IC50) were determined in cancer cell lines using CellTiter-Glo luminescent cell viability assay after incubation with different concentrations of ADC or control. Each cell line was treated with ADC, a standard chemotherapy drug as reference control and culture medium as vehicle control. A549 and Calu-6 are negative control cell lines that do not express the protein target Trop2. All remaining cell lines express some of the target protein Trop2 on RNA and / or protein levels. All the cells were cultured in the media supplemented with 10-15% FBS, at a temperature of 37oC, 5% CO2and 95% humidity.CellTiter-Glo® Luminescent Cell Viability Assay (Cat# G7572, Promega) was used. Determination of the half maximal inhibition concentration IC50 1. Harvest cells during the logarithmic growth period and count cell number using Count-star. 2. Adjust cell concentrations to 4.44×104cells / mL with respective culture medium. 3. Add 90 μL cell suspensions to two 96-well plates (plates A and B) with the final cell density of 4×103cells / well (cell concentration may be adjusted according to the data base or density optimization assay). 4a. Next day: For the plates of T0 reading: 1) Add 10 μL culture medium to each well of plate A for T0 reading. 2) Equilibrate the plate and its content at RT for approximately 30 min. 3) Add 50 μL CellTiter-Glo reagent to each well. 4) Mix content for 5 min on an orbital shaker to induce cell lysis. 5) Allow the plate to incubate at RT for 20 min to stabilize luminescent signal. 6) Record luminescence (T0) using EnVision Multi Label Reader. 4b. For the plates of test reading: 1) Prepare 10×solution of ADC (Top working concentration: 200 nM of ADC in media with 10-fold serial dilutions to achieve 9 dose levels. 2) Prepare 10×reference control solutions Cisplatin (Top working concentration: 100 μM in media with 3.16-fold serial dilutions to achieve 9 dose levels. 3) Dispense 10 μL (10×) drug solution of both ADC and reference control in each well (triplicate for each drug concentration) of the plate B. 4) Incubate the test plate B for 120 hours in the humidified incubator at 37°C with 5% CO2. 5) Equilibrate the plate and its content at RT for approximately 30 min. 6) Add 50 μL CellTiter-Glo reagent to each well. 7) Mix contents for 5 min on an orbital shaker to induce cell lysis. 8) Allow the plates to incubate at RT for 20 min to stabilize luminescent signal. 9) Record luminescence (T5) using EnVision Multi Label Reader. Data Analysis The data were displayed or analyzed using GraphPad Prism 5.0. In order to calculate absolute IC50 (EC50), a dose-response curve will be fitted using nonlinear regression model with a sigmoidal dose response. The formula for calculating surviving rate is shown below and the absolute IC50 (EC50) will be calculated according to the dose-response curve generated by GraphPad. The surviving rate (%) = (LumTest article-LumMedium control) / (LumNon-treated-LumMediumcontrol) ×100%. Table B1. cytotoxicity screen against a panel of 70 cell lines . Table B2. cytotoxicity data on a representative list of 30 responsive cell lines Table B3. Representative cell lines that are responsive to anti-Trop2 PH1 ADC and mutations of these cell lines. Example 12 Durable regression in Trop2 positive gastric xenograft model In this Example, using subcutaneous NCI-N87 gastric cancer xenograft model in female BALB / c nude Mice, the efficacy of Trop2 PH1 ADCs (M2.8 mAb conjugated with PH1 payload, also referred to as M2.8 L22 ADCs) at DAR2 and DAR4 were tested against Trodelvy (pharmaceutical-grade IMMU-132) which was used for human clinical trials and subsequently approved for human use. Even at a lower dose (3mpk vs 10mpk) and DAR (2 or 4, vs 8), Trop2 PH1 ADCs outperformed pharmaceutical-grade IMMU-132. Methods Cell Culture The NCI-N87 tumor cell line was maintained in vitro in RPMI1640 medium supplemented with 10% fetal bovine serum at 37 ºC in an atmosphere of 5% CO2in air. The tumor cells were routinely sub-cultured twice weekly by trypsin-EDTA treatment. The cells growing in an exponential growth phase were harvested and counted for tumor inoculation. Tumor Inoculation Each mouse was inoculated subcutaneously in the right flank region with tumor cells (1*107) in 0.1 ml of PBS mixed with Matrigel (1:1) for tumor development. Randomization The randomization was started when the mean tumor size reached approximately 192.40 mm3.100 mice were enrolled in the study. All animals were randomly allocated to 12 study groups. Randomization was performed based on "Matched distribution" method (StudyDirectorTM software, version 3.1.399.19). Observation and Data Collection After tumor cells inoculation, the animals were checked daily for morbidity and mortality. During routine monitoring, the animals were checked for any effects of tumor growth and treatments on behavior such as mobility, food and water consumption, body weight gain / loss (Body weights were measured twice per week after randomization), eye / hair matting and any other abnormalities. Mortality and observed clinical signs were recorded for individual animals in detail. Tumor volumes were measured twice per week after randomization in two dimensions using a caliper, and the volume was expressed in mm3 using the formula: V = (L x W x W) / 2, where V is tumor volume, L is tumor length (the longest tumor dimension) and W is tumor width (the longest tumor dimension perpendicular to L). Dosing as well as tumor and body weight measurements were conducted in a Laminar Flow Cabinet. The treatment was initiated on the same day of randomization (day 6) per study design. Tumor growth inhibition (TGI): TGI% is an indication of antitumor activity and expressed as: TGI (%) =100 x (1-T / C). T and C are the mean tumor volume (or weight) of the treated and control groups, respectively, on a given day. Statistical analysis of the difference in mean tumor volume among the groups was conducted using the methods below: Use the data collected on the last observation day for every single group in despite diverse individual termination date. Statistical Analysis To compare tumor volumes of different groups at a pre-specified day, Bartlett's test was first used to check the assumption of homogeneity of variance across all groups. When the p-value of Bartlett's test was >= 0.05, a one-way ANOVA was performed to test overall equality of means across all groups. If the p-value of the one-way ANOVA was < 0.05, a post hoc testing was performed by running Tukey's HSD (honest significant difference) tests for all pairwise comparisons, and Dunnett's tests for comparing each treatment group with the vehicle group. When the p-value of Bartlett's test was <0.05, a Kruskal-Wallis test was performed to test overall equality of medians among all groups. If the p-value the Kruskal- Wallis test was <0.05, post hoc testing was performed by running Conover's non-parametric test for all pairwise comparisons or for comparing each treatment group with the vehicle group, both with single-step p-value adjustment. In addition, pairwise comparisons were performed without multiple comparison correction and nominal / uncorrected p-values directly from Welch's t-test or Mann-Whitney U test were reported. Specifically, Bartlett's test was first used to check the assumption of homogeneity of variance for a pair of groups. When the p-value of Bartlett's test was ≥0.05, a Welch's t-test was performed, otherwise a Mann- Whitney U test was performed, to obtain nominal p-values. All statistical analyses had been done in R-a language and environment for statistical computing and graphics (version 3.3.1). All tests were two-sided unless otherwise specified, and p-values of <0.05 were regarded as statistically significant. Results In a Trop2 positive tumor model (nude mice bearing human NCI-N87 gastric tumors with expression level IHC3+), mice were dosed at dosing regimen of QW for 2 weeks (QWx2). Horizontal dotted line indicates mean tumor volume of 200 mm3size at which treatment was initiated. Tumor shrinkage below this line was considered regression. Tumor sizes were monitored. Early efficacy for M2.8 L22 ADC DAR4 manifests as about 90% TGI and was observed from D21 through D41. Although, the TGI by Trodelvy was ~80%, there was no statistical difference in the inhibitions caused by the 2 agents during this early period. Long term tumor regression (TR) was observed in 50% of treated mice over a period of about 5 months in the group treated with Trop2 PH1 (DAR4) ADC at 3mg / kg (Figure 16). Stable disease was observed in 50% of treated mice over a period of about 5 months in the group treated with Trop2 PH1 (DAR2) ADC at 3mg / kg. Both treatment groups of Trop2 PH1 outperformed the treatment group of IMMU-132* at lower DAR (2 or 4 vs 7.6) and at lower dose (3mg / kg vs 10 mg / kg). IMMU-132* represents clinical grade IMMU-132 (Sacituzumab govitecan). Conclusion M2.8 L22 AD...

Claims

WHAT IS CLAIMED IS:

1. An antibody-drug conjugate compound comprising an antibody covalently attached to a drug moiety directly (i.e., without a linker) or through a linker of Formula I:or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), whereinL is a linker; n is 0 or 1; p is 1 to 20; and Ab is an antibody.

2. The antibody-drug conjugate compound of claim 1 comprising an antibody covalently attached to a drug moiety directly (i.e., without a linker) or through a linker of Formula I:or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), wherein the drug moiety is:L is a linker; n is 0 or 1; p is 1 to 20; and Ab is an antibody that binds to Trop2.

3. The antibody-drug conjugate compound of claim 1 or claim 2, wherein n is 0 (i.e., the linker (L) is absent).

4. The antibody-drug conjugate compound of claim 1 or claim 2, wherein the antibody is attached to the drug moiety by a sidechain nitrogen of a lysine residue of the antibody.

5. The antibody-drug conjugate compound of claim 1, wherein n is 1.

6. The antibody-drug conjugate of any one of claims 1, 2 or 5, wherein the linker L has the formula -X1-X2-X3-X4- wherein, X1is a bond, -N(Ra)-, -N(Ra)-N(Ra)-, -O-, -N-O-, -S-, -C(=O)-, -C(=O)N(Ra), C(=S)N(Ra)-, -C(=O)O-, -C(=O)S-, -N(Ra)SO2-, -OC(=O)N(Ra)-, -(Ra)HC(=O)N(Ra)-, or -N(Ra)C(=S)N(Ra)-, wherein Rais H or (C1-C6)alkyl; X2is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), -N(Rb)-, a divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl wherein Rbis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S), and wherein the divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl is optionally substituted with one more halo or (C1-C6)alkyl; X3is a bond or a peptide (e.g., a peptide comprising 1, 2, 3, 4, 5, or 6 amino acid residues); andX4is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 60 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), or -N(Rc)- wherein Rcis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S); wherein at least one of X1, X2, or X3is not a bond.

7. The antibody-drug conjugate compound of claim 1 or claim 2, wherein n is 0 (i.e., L is absent) or n is 1 and L is a linker selected from the group consisting of:, wherein: each m is independently 1, 2, 3, or 4; each n1 is independently 1, 2, 3, 4, 5, or 6; each p1 is independently 1, 2, 3, 4, 5, or 6; each t is independently 1, 2, 3, or 4; each n2 is independently 1, 2, 3, 4, 5, or 6; each p2 is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; each q2 is independently 1, 2, 3, 4, 5, or 6; each s is independently 1, 2, 3, or 4; and each AA1 and AA2 are independently a sidechain of an amino acid.

8. The antibody-drug conjugate compound of claim 1, wherein n is 0 (i.e., L is absent) or n is 1 and L is a linker selected from the group consisting of:O.

9. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulin heavy chain variable region polypeptide and an immunoglobulin light chain variable region polypeptide, wherein: the immunoglobulin heavy chain variable region polypeptide comprises a complementarity determining region 1 (HCDR1) comprising an amino acid sequence that is at least 75% identical to NYGMN (SEQ ID NO: 14), a complementarity determining region 2 (HCDR2) comprising an amino acid sequence that is at least 75% identical to WINTKTGEPTYAEEFKG (SEQ ID NO: 16) or WINTKTGEPTYAQEFTG (SEQ ID NO: 21), and a complementarity determining region 3 (HCDR3) comprising an amino acid sequence that is at least 75% identical to GGYGSSYWYFDV (SEQ ID NO: 18); and / or the immunoglobulin light chain variable region polypeptide comprises a complementarity determining region 1 (LCDR1) comprising an amino acid sequence that is at least 75% identical to KASQDVSIAVA (SEQ ID NO: 27), a complementarity determining region 2 (LCDR2) comprising an amino acid sequence that is at least 75% identical to SASYRYT (SEQ ID NO: 29), and a complementarity determining region 3 (LCDR3) comprising an amino acid sequence that is at least 75% identical to QQHYITPLT (SEQ ID NO: 31).

10. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulin heavy chain variable region polypeptide and an immunoglobulin light chain variable region polypeptide, wherein: the immunoglobulin heavy chain variable region polypeptide comprises a complementarity determining region 1 (HCDR1) comprising an amino acid sequence that is at least 85% identical to NYGMN (SEQ ID NO: 14), a complementarity determining region 2 (HCDR2) comprising an amino acid sequence that is at least 85% identical to WINTKTGEPTYAEEFKG (SEQ ID NO: 16) or WINTKTGEPTYAQEFTG (SEQ ID NO: 21), and a complementarity determining region 3 (HCDR3) comprising an amino acid sequence that is at least 85% identical to GGYGSSYWYFDV (SEQ ID NO: 18); and / orthe immunoglobulin light chain variable region polypeptide comprises a complementarity determining region 1 (LCDR1) comprising an amino acid sequence that is at least 85% identical to KASQDVSIAVA (SEQ ID NO: 27), a complementarity determining region 2 (LCDR2) comprising an amino acid sequence that is at least 85% identical to SASYRYT (SEQ ID NO: 29), and a complementarity determining region 3 (LCDR3) comprising an amino acid sequence that is at least 85% identical to QQHYITPLT (SEQ ID NO: 31).

11. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulin heavy chain variable region polypeptide and an immunoglobulin light chain variable region polypeptide, wherein: the immunoglobulin heavy chain variable region polypeptide comprises a complementarity determining region 1 (HCDR1) comprising NYGMN (SEQ ID NO: 14), a complementarity determining region 2 (HCDR2) comprising WINTKTGEPTYAEEFKG (SEQ ID NO: 16) or WINTKTGEPTYAQEFTG (SEQ ID NO: 21), and a complementarity determining region 3 (HCDR3) comprising GGYGSSYWYFDV (SEQ ID NO: 18); and / or the immunoglobulin light chain variable region polypeptide comprises a complementarity determining region 1 (LCDR1) comprising KASQDVSIAVA (SEQ ID NO: 27), a complementarity determining region 2 (LCDR2) comprising SASYRYT (SEQ ID NO: 29), and a complementarity determining region 3 (LCDR3) comprising QQHYITPLT (SEQ ID NO: 31).

12. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulin heavy chain variable region polypeptide and an immunoglobulin light chain variable region polypeptide, wherein: the immunoglobulin heavy chain variable region polypeptide comprises a complementarity determining region 1 (HCDR1) comprising SEQ ID NO: 14, a complementarity determining region 2 (HCDR2) comprising SEQ ID NO: 16, and a complementarity determining region 3 (HCDR3) comprising SEQ ID NO: 18.

13. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulinheavy chain variable region polypeptide and an immunoglobulin light chain variable region polypeptide, wherein: the immunoglobulin heavy chain variable region polypeptide comprises a complementarity determining region 1 (HCDR1) comprising SEQ ID NO: 14, a complementarity determining region 2 (HCDR2) comprising SEQ ID NO: 21, and a complementarity determining region 3 (HCDR3) comprising SEQ ID NO: 18.

14. The antibody-drug conjugate compound of any one of claims 1-8, the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulin heavy chain variable region polypeptide and an immunoglobulin light chain variable region polypeptide, wherein: the immunoglobulin light chain variable region polypeptide comprises a complementarity determining region 1 (LCDR1) comprising SEQ ID NO: 27, a complementarity determining region 2 (LCDR2) comprising SEQ ID NO: 29, and a complementarity determining region 3 (LCDR3) comprising SEQ ID NO: 31.

15. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 1-4, and an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 5-6.

16. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 1-4, and an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 5-6.

17. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 1-4, and an immunoglobulin light chain variableregion polypeptide comprising an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 5-6.

18. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody and comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 1-4, and an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 5-6.

19. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 1-4, and an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 5-6.

20. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody or fragment thereof and comprises an immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 2 or 4, and an immunoglobulin light chain variable region polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 5-6.

21. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody and comprises an immunoglobulin heavy chain polypeptide comprising a human IgG1, IgG2, IgG3, or IgG4 Fc domain.

22. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody and comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 7, 9, 10, 11, or 34-37, and an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 8 or 12.

23. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody and comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 7, 9, 10, 11, or 34-37, and an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 8 or 12.

24. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody and comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 7, 9, 10, 11, or 34-37, and an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 8 or 12.

25. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody and comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 7, 9, 10, 11, or 34-37, and an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 8 or 12.

26. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody and comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 7, 9, 10, 11, or 34-37.

27. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody and comprises an immunoglobulin light chain polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 8 or 12.

28. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody and comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is any one of SEQ ID NOs: 7, 10, 35, or37, and an immunoglobulin light chain polypeptide comprising an amino acid sequence that is any one of SEQ ID NOs: 8 or 12.

29. The antibody-drug conjugate compound of any one of claims 1-8, wherein the antibody is an anti-Trop2 antibody and comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is any one of SEQ ID NOs: 7, or 37, and an immunoglobulin light chain polypeptide comprising an amino acid sequence of SEQ ID NO:

8.

30. An antibody or fragment thereof comprising an immunoglobulin heavy chain variable region polypeptide and an immunoglobulin light chain variable region polypeptide, wherein: the immunoglobulin heavy chain variable region polypeptide comprises a complementarity determining region 1 (HCDR1) comprising an amino acid sequence that is at least 90% identical to NYGMN (SEQ ID NO: 14), a complementarity determining region 2 (HCDR2) comprising an amino acid sequence that is at least 90% identical to WINTKTGEPTYAQEFTG (SEQ ID NO: 21), and a complementarity determining region 3 (HCDR3) comprising an amino acid sequence that is at least 90% identical to GGYGSSYWYFDV (SEQ ID NO: 18); and / or the immunoglobulin light chain variable region polypeptide comprises a complementarity determining region 1 (LCDR1) comprising an amino acid sequence that is at least 90% identical to KASQDVSIAVA (SEQ ID NO: 27), a complementarity determining region 2 (LCDR2) comprising an amino acid sequence that is at least 90% identical to SASYRYT (SEQ ID NO: 29), and a complementarity determining region 3 (LCDR3) comprising an amino acid sequence that is at least 90% identical to QQHYITPLT (SEQ ID NO: 31).

31. The antibody or fragment thereof of claim 30, wherein: the immunoglobulin heavy chain variable region polypeptide comprises a complementarity determining region 1 (HCDR1) comprising NYGMN (SEQ ID NO: 14), a complementarity determining region 2 (HCDR2) comprising WINTKTGEPTYAQEFTG (SEQ ID NO: 21), and a complementarity determining region 3 (HCDR3) comprising GGYGSSYWYFDV (SEQ ID NO: 18); and / or NO:27), a complementarity determining region 2 (LCDR2) comprising SASYRYT (SEQ ID NO: 29), and a complementarity determining region 3 (LCDR3) comprising QQHYITPLT (SEQ ID NO: 31).

32. The antibody or fragment thereof of any one of claims 30-31, wherein: the immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:4, and the immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 5-6; or the immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:4, and the immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 6.

33. The antibody or fragment thereof of any one of claims 30-31, wherein: the immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 97% identical to SEQ ID NO:4, and the immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 5-6 or the immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 97% identical to SEQ ID NO:4, and the immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 6.

34. The antibody or fragment thereof of any one of claims 30-31, wherein: the immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 99% identical to SEQ ID NO:4, and the immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 5-6; or the immunoglobulin heavy chain variable region polypeptide comprising an amino acid sequence that is at least 99% identical to SEQ ID NO:4, and the immunoglobulin light chain variable region polypeptide comprising an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 6.

35. The antibody or fragment thereof of any one of claims 30-31, wherein: the immunoglobulin heavy chain variable region polypeptide comprising SEQ ID NO:4, and the immunoglobulin light chain variable region polypeptide comprising SEQ ID NO: 5 or 6; or the antibody or fragment thereof of any one of claims 30-31, wherein: the immunoglobulin heavy chain variable region polypeptide comprising SEQ ID NO:4, and the immunoglobulin light chain variable region polypeptide comprising SEQ ID NO:

6.

36. The antibody of any one of claims 30-31, wherein the antibody comprises an immunoglobulin heavy chain polypeptide comprising a human IgG1, IgG2, IgG3, or IgG4 Fc domain.

37. The antibody of any one of claims 30-31, wherein the antibody comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 7, or 37, and an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 8 or 12.

38. The antibody of any one of claims 30-31, wherein the antibody comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 7, or 37, and an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 97% identical to any one of SEQ ID NOs: 8 or 12.

39. The antibody of any one of claims 30-31, wherein the antibody comprises an immunoglobulin heavy chain polypeptide comprising an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 7, or 37, and an immunoglobulin light chain polypeptide comprising an amino acid sequence that is at least 99% identical to any one of SEQ ID NOs: 8 or 12.

40. The antibody of any one of claims 30-31, wherein the antibody comprises an immunoglobulin heavy chain polypeptide comprising any one of SEQ ID NOs: 7, or 37, and an immunoglobulin light chain polypeptide comprising any one of SEQ ID NOs: 8 or 12.

41. The antibody of any one of claims 30-31, wherein the antibody comprises an immunoglobulin heavy chain polypeptide comprising any one of SEQ ID NOs: 7, or 37, and an immunoglobulin light chain polypeptide comprising SEQ ID NO: 8.

42. A compound of formula IIII or a salt thereof, whereinW is a leaving group or -L-X;L is a linker; andX is a reactive group.

43. The compound of claim 42, wherein W is a leaving group.

44. The compound of claim 42 or 43, wherein the leaving group is halo, -O(Ci- Ce)alkyl, -Oaryl, -Oheteroaryl or -Oheterocylcylyl, wherein the -O(Ci-Ce)alkyl, -Oaryl, Oheteroaryl or Oheterocylcylyl are each optionally substituted with one or more substituents independently selected from the group consisting of oxo, halo, (Ci-Ce)alkyl and -O(Ci- Ce)alkyl.

45. The compound of claim 42, wherein W together with the carbonyl group to which it is attached forms an activated ester.

46. The compound of claim 42, wherein W is -Ophenyl optionally substituted with one or more halo or W is 2,5, dioxopyrollidinyloxy.

47. The compound of claim 42, wherein W is -Ophenyl optionally substituted with one or more halo.

48. The compound of claim 42, wherein W is -Ophenyl optionally substituted with one or more fluoro.

49. The compound of claim 42, wherein W is a 2,3,5,6,-tetrafluorophenoxy.

50. The compound of claim 42, wherein W is 2,5, dioxopyrollidinyloxy.

51. The compound of claim 42, wherein W is L-X.

52. The compound of claim 42 or claim 51, wherein L has the formula -X1-X2-X3-X4- wherein, X1is a bond, -N(Ra)-, -N(Ra)-N(Ra)-, -O-, -N-O-, -S-, -C(=O)-, -C(=O)N(Ra), C(=S)N(Ra)-, -C(=O)O-, -C(=O)S-, -N(Ra)SO2-, -OC(=O)N(Ra)-, -(Ra)HC(=O)N(Ra)-, or -N(Ra)C(=S)N(Ra)-, wherein Rais H or (C1-C6)alkyl; X2is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 30 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), -N(Rb)-, a divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl wherein Rbis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), and thioxo(=S), and wherein the divalent 6-10 membered aryl or a divalent 5-20 membered heteroaryl is optionally substituted with one more halo or (C1-C6)alkyl; X3is a bond or a peptide (e.g., a peptide comprising 1, 2, 3, 4, 5, or 6 amino acid residues); and X4is a bond or a divalent, branched or unbranched, saturated or unsaturated, hydrocarbon chain having from 1 to 60 carbon atoms, wherein one or more of the carbon atoms is optionally replaced by (-O-), (-S-), or -N(Rc)- wherein Rcis H or (C1-C6)alkyl, wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, oxo(=O), andthioxo(=S); wherein at least one of X1, X2, or X3is not a bond.

53. The compound of any one of claims 42, 51, or 52 wherein W is selected from the group consisting of .,wherein: each m is independently 1, 2, 3, or 4; each n1 is independently 1, 2, 3, 4, 5, or 6; each p1 is independently 1, 2, 3, 4, 5, or 6; each t is independently 1, 2, 3, or 4; each n2 is independently 1, 2, 3, 4, 5, or 6; each p2 is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; each q2 is independently 1, 2, 3, 4, 5, or 6; each s is independently 1, 2, 3, or 4; and each AA1 and AA2 are independently a sidechain of an amino acid.

54. The compound of any one of claims 42, 51, or 52, wherein each X is independently selected from an ester, activated ester, haloacetamide, halo, and disulfanylheteroaryl.

55. The compound of any one of claims 42, 51, or 52, wherein each X is selected from 2,3,5,6,-tetrafluorophenoxycarbonyl, 2,5-dioxopyrollidinyloxycarbonyl, disulfanylpyridinyl, and bromoacetyl.

56. The compound of any one of claims 42, 51, or 52, wherein each X is selected from 2,3,5,6,-tetrafluorophenoxycarbonyl and bromoacetyl.

57. The compound of claim 42 selected from the group consisting of,,or a salt thereof.

58. A compound of selected from the group consisting of , ,or a salt thereof (e.g., a pharmaceutically acceptable salt thereof).

59. The antibody-drug conjugate compound according to any one of claims 1-29, wherein p is 1, 2, 3, 4, 5, 6, 7, or 8.

60. The antibody-drug conjugate compound according any one of claims 1-29, comprising a mixture of the antibody-drug conjugate compounds, wherein the average drug loading per antibody in the mixture of antibody-drug conjugate compounds is about 1 to about 5.

61. A pharmaceutical composition comprising the antibody-drug conjugate compound according to any one of claims 1-29, 59, or 60 and a pharmaceutically acceptable diluent, carrier or excipient.

62. A method for treating cancer in a patient in need thereof, comprising administering a therapeutically effective amount of the antibody drug conjugate compound of any one of claims 1-29, 59, or 60, or the pharmaceutical composition of claim 61 to the patient in need thereof.

63. The method of claim 62, wherein the cancer is selected from lung cancer, non-small cell lung cancer, pancreatic cancer, esophageal cancer, gastric cancer, bladder cancer, ovarian cancer, breast cancer, uterine cancer and head and neck cancer.

64. The method of claim 62, wherein the cancer is selected from lung cancer (e.g., non- small cell lung cancer, lung adenocarcinoma, and lung large cell carcinoma), pancreaticcancer, esophageal cancer, gastric cancer, bladder cancer, ovarian cancer, breast cancer, and uterine cancer.

65. The method of any one of claims 62-64, wherein the patient has Trop2 positive tumor cells.

66. The method of any one of claims 62-64, wherein the patient has tumor cells comprising one or more mutation that is a loss-of-function mutation in a tumor suppressor gene, and / or a gain-of-function mutation in an oncogenic driver gene and / or amplification of an oncogenic driver gene.

67. The method of any one of claims 62-66, wherein the patient has tumor cells that comprises one or more mutation in a gene selected from the group consisting of KRAS, BRAF, EGFR, ERBB2, ERBB3, APC, CNGA2, ARID1A, SLC34A2, ROS1, FGFR3, TACC3, BAIAP2L1, PIK3CA, PIK3R1, BRCA2, PTEN, STK11, CDKN2A, SMAD4, TP53, UGT2B17, SMARCA2, and SMARCA4.

68. The method of claim 66 or claim 67, wherein the one or more mutation comprises a point mutation.

69. The method of claim 67, wherein the one or more mutation comprises a mutation selected from the group consisting of KRas G12V, BRAF G466V, EGFR L861Q, PIK3CA E545K, APC R1450*, PIK3R1 R386fs, PIK3R1 R639ter, TP53 V218, ARID1A L649fs / R693ter and SMARCA4 G1162C.

70. The method of claim 66 or claim 67, wherein the one or more mutation comprises a gain-of-function mutation.

71. The method of claim 66 or claim 67, wherein the patient has tumor cell that comprises one or more mutation in a gene selected from the group consisting of KRAS, BRAF, EGFR, SLC34A2, ROS1, FGFR3, TACC3, BAIAP2L1, PIK3CA, PIK3R1, and BRCA2.

72. The method of claim 66 or claim 67, wherein the one or more mutation comprises a loss-of-function mutation.

73. The method of claim 66 or claim 67, wherein the subject has tumor cell that comprises one or more mutation in a gene selected from the group consisting of PTEN, STK11, CDKN2A, SMAD4, and TP53.

74. The method of claim 66 or claim 67, wherein the one or more mutation comprises fusion mutation of two genes.

75. The method of claim 74, wherein the one or more mutation comprise fusion mutation selected from the group consisting of SLC34A2-ROS1, FGFR3-TACC3, and FGFR3- BAIAP2L1.

76. The method of claim 66 or claim 67, wherein the one or more mutation comprises a BRCA-deficient mutation, FGFR3 gain-of-function mutation, TP53 loss-of-function mutation, or SMARCA4 loss-of-function mutation.

77. The method of claim 66 or claim 67, wherein one or more copy number variations (CNV) comprises a partial or total loss of PTEN, STK11, CDKN2A, CNGA2, SMAD4, UGT2B17; or gain / amplification of ERBB2, ERBB3, PIK3CA.

78. The method of any one of claims 62-77, wherein the patient has HPV positive tumor cells.

79. The method of any one of claims 62-77, wherein the patient has HPV39 positive tumor cells.

80. The method of any one of claims 62-79, wherein the patient is unresponsive to standard-of-care (SOC) therapy.

81. The method of any one of claims 62-80, wherein the patient’ s tumor is resistant to MEK or BET inhibitor therapy (e.g.,in Lung adenocarcinoma), anti-EGFR therapy (e.g., in NSCLC), or multi-kinase inhibitor therapies (e.g., such as Sorafenib or AZ628 inhibitors in Gastric cancer).

82. An article of manufacture comprising a pharmaceutical composition of claim 61, a container, and a package insert or label indicating that the pharmaceutical composition can be used to treat cancer.

83. Use of an antibody-drug conjugate compound according to any one of claims 1-29, 59, or 60, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of cancer in a mammal.

84. An antibody-drug conjugate compound according to any one of claims 1-29, 59, or 60, or a pharmaceutically acceptable salt thereof, for use in the therapeutic treatment of cancer.

85. Use of an antibody-drug conjugate compound according to any one of claims 1-29, 59, or 60, or a pharmaceutically acceptable salt thereof, for medical therapy.

86. A compound selected from the group consisting of:wherein: P is an amine nitrogen protecting group; each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1-C6)alkyl; and R2is a (C1-C6)alkyl or phenyl, wherein the phenyl is optionally substituted with one or more halo or nitro; or a salt thereof.

87. The compound of claim 86 selected from the group consisting of:or a salt thereof.

88. The compound of claim 86 selected from the group consisting of:or a salt thereof.

89. The compound of claim 86 selected from the group consisting of:or a salt thereof.

90. A method for preparing a compound of formula 8*:or a salt thereof, comprising converting a corresponding compound of formula 7*:7* or a salt thereof, to the compound of formula 8* or a salt thereof.

91. A method for preparing a compound of formula 7*:7* or a salt thereof, comprising converting a corresponding compound of formula 6a*:6a* or a salt thereof, to the compound of formula 7* or a salt thereof, wherein R2is a (C1-C6)alkyl.

92. The method of claim 90, wheren the compound of formula 7* or a salt thereof is prepared, comprising converting a corresponding compound of formula 6a*:6a* or a salt thereof, to the compound of formula 7* or a salt thereof, wherein R2is a (C1-C6)alkyl.

93. The method of claim 91 or claim 92, wherein the compound of formula 6a* is a compound of formula 6*:6* or a salt thereof.

94. A method for preparing a compound of formula 6a*:or a salt thereof, comprising converting a corresponding compound of formula 5a*:5a* or a salt thereof, to the compound of formula 6a* or a salt thereof, wherein: each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl; and R2is a (C1-C6)alkyl.

95. The method of claim 91 or claim 92, wherein the compound of formula 6a* or a salt thereof is prepared, comprising converting a corresponding compound of formula 5a*:5a* or a salt thereof, to the compound of formula 6 or a salt thereof, wherein each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1-C6)alkyl.

96. The method of claim 94 or claim 95, wherein the compound of formula 6a* is a compound of formula 6*:6* or a salt thereof.

97. The method of claim 94 or claim 95, wherein the compound of formula 5a* is a compound of formula 5*:5* or a salt thereof .

98. The method of claim 94 or claim 95, wherin the compound of formula 6a* is prepared, comprising reacting the compound of formula 5a* or a salt thereof, with a compound of formula Ba*:or a salt thereof, to the compound of formula 6a*, wherein R2is a (C1-C6)alkyl.

99. The method of claim 98, wherein the compound of formula Ba* is a compound of formula B*:or a salt thereof.

100. The method of claim 96, wherein the compound of formula 6* is prepared comprising reacting the compound of formula 5a* or a salt thereof, with a compound of formula B*:or a salt thereof, to provide the compound of formula 6*.

101. A method for preparing a compound of formula 5a*:5a* or a salt thereof, comprising converting a corresponding compound of formula 4a*:or a salt thereof, to the compound of formula 5a* or a salt thereof, wherein each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1-C6)alkyl.

102. The method of claim 94 or claim 95, wheren the compound of formula 5a* or a salt thereof is prepared, comprising converting a corresponding compuonf of formula 4a*:4a* or a salt thereof, to the compound of formula 5a* or a salt thereof.

103. The method of claim 101 or claim 102, wherein the compound of formula 5a* is a compound of formula 5*:5* or a salt thereof, and the compound of formula 4a* is a compound of formula 4*:4* or a salt thereof.

104. The method of claim 101 or claim 102, wherein the compound of formula 5a* is prepared comprising reacting the compound of formula 4a* or salt thereof with a compound of formulaA* or salt thereof, to provide the compound of formula 5a* or a salt thereof.

105. The method of claim 103, comprising reacting the compound of formula 4* or salt thereof, with a compound of formula A*:A* or salt thereof, to provide the compound of formula 5* or a salt thereof.

106. A method for preparing a compound of formula 4a*:4a* or a salt thereof, comprising converting a corresponding compound of formula 3a*:3a* or a salt thereof, to the compound of formula 4a* or a salt thereof, wherein: P is an amine nitrogen protecting group; and each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl.

107. The method of claim 101 or claim 102, wheren the compound of formula 4a* or a salt thereof is prepared, comprising converting a corresponding compound of formula 3a*:3a* or a salt thereof, to the compound of formula 4a* or a salt thereof, wherein P is an amine nitrogen protecting group; and each R1is independently a (C1-C6)alkyl, or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl.

108. The method of claim 106 or claim 107, wherein the compound of formula 4a* or a salt thereof is a compound of formula 4*:4* or a salt thereof, and the compound of formula 3a* or a salt thereof is a compound of formula 3*:3* or a salt thereof.

109. A method for preparing a compound of formula 3a*:3a* or a salt thereof, comprising converting a corresponding compound of formula 2a*:2a* or a salt thereof, to the compound of formula 3a* or a salt thereof, wherein: P is an amine nitrogen protecting group; and each R1is independently a (C1-C6)alkyl or two R1groups together with the atoms to which they are attached form a heterocyclyl optionally substituted with one or more (C1- C6)alkyl.

110. The method of claim 21 or claim 22, wherein the compound of formula 3a* or a salt thereof is prepared, comprising converting a corresponding compound of formula 2a*:2a* or a salt thereof, to the compound of formula 3a* or a salt thereof, wherein P is an amine nitrogen protecting group.

111. The method of claim 109 or claim 110, wherein the compound of formula 3a* or a salt thereof, is a compound of formula 3*:3* or a salt thereof, and the compound of formula 2a* is a compound of formula 2*:or a salt thereof.

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