ANTI-HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY (ANTI-hEGFR), DRUG-ANTIBODY CONJUGATE COMPRISING IT, AND NUCLEIC ACID ENCODING IT

Abstract

Antibodies and antibody-drug conjugates (ADCs) against epidermal growth factor (EGFR), including compositions and methods for using said antibodies and ADCs.

Description

ANTI-HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR (ANTI-hEGFR) ANTIBODY, DRUG-ANTIBODY CONJUGATE COMPRISING IT, AND NUCLEIC ACID ENCODING IT RELATED APPLICATIONS This application invokes the priority benefit of U.S. Provisional Application No. 61 / 968.819, filed on March 21, 2014. The contents of the above-mentioned priority application are incorporated herein in full by reference. LIST OF SEQUENCES This application contains a Sequence List that was submitted electronically in ASCII format and is incorporated herein in its entirety for reference purposes. This ASCII copy, created on March 12, 2015, is named 117813-06220_SL.txt and is 110,863 bytes in size. BACKGROUND OF THE INVENTION The human epidermal growth factor receptor (also known as HER-1 or Erb-B1, and referred to herein as “EGFR”) is a 170 kDa transmembrane receptor encoded by the proto-oncogene c-erbB, and exhibits intrinsic tyrosine kinase activity (Modjtahedi et al., Br. J. Cancer 73:228-235 (1996); Herbst and Shin, Cancer 94:1593-1611 (2002)). The SwissProt database entry P00533 provides the sequence of human EGFR. EGFR regulates various cellular processes through tyrosine kinase-mediated signal transduction pathways, including, but not limited to, activation of signal transduction pathways that control cell proliferation, differentiation, cell survival, and apoptosis. angiogenesis, mitogenesis, and metastasis (Atalay et al., Ann. Oncology 14:1346-1363 (2003); Tsao and Herbst, Signal 4:4-9 (2003); Herbst and Shin, Cancer 94:1593-1611 (2002); Modjtahedi et al., Br. J. Cancer 73:228-235 (1996)). Known EGFR ligands include EGF, TGFA / TGF-alpha, amfiregulin, epigen / EPGN, BTC / betacoelin, epiregulin / EREG, and heparin-binding HBEGF / EGF. Ligand binding to EGFR initiates homo- and / or heterodimerization of the receptor and autophosphorylation of key cytoplasmic residues. Phosphorylated EGFR recruits adaptor proteins such as GRB2, which in turn activates complex downstream signaling cascades, including at least the following downstream signaling cascades: RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC, and STAT modules. This autophosphorylation also exerts downstream activation and signaling by several other proteins that associate with phosphorylated tyrosines through their phosphotyrosine-binding S2 domains. These downstream signaling proteins initiate several signal transduction cascades, primarily the MAPK, Akt, and JNK pathways, leading to cell proliferation.Ligand binding to EGFR can also activate the NF-κB signaling cascade. Ligand binding also directly phosphorylates other proteins such as RGS16, activating its GTPase activity and potentially coupling EGF receptor signaling to G protein-coupled receptor signaling. Ligand binding also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1 / β-catenin. EGFR overexpression has been reported in various human malignancies, including bladder, brain, head and neck, pancreatic, lung, breast, ovarian, colon, prostate, and other cancers. Kidney. (Atalay et al., Ann. Oncology 14:1346-1363 (2003); Herbst and Shin, Cancer 94:1593-1611 (2002); and Modjtahedi et al., Br. J. Cancer 73:228-235 (1996)). In many of these conditions, EGFR overexpression is correlated with a poor prognosis for patients. (Herbst and Shin, Cancer 94:1593-1611 (2002); and Modjtahedi et al., Br. J. Cancer 73:228-235 (1996)). EGFR is also expressed in cells of normal tissues, particularly epithelial tissues of the skin, liver, and gastrointestinal tract, although generally at lower levels than in malignant cells (Herbst and Shin, Cancer 94:1593-1611 (2002)). A significant proportion of tumors containing amplifications of the EGFR gene (i.e., multiple copies of the EGFR gene) also co-express a truncated version of the receptor (Wikstrand et al. (1998) J. Neurovirol. 4, 148-158) known as de2-7 EGFR, AEGFR, EGFRvIII, or A2-7 (terms used herein as synonyms) (Olapade-Olaopa et al. (2000) Br. J. Cancer. 82, 186-94). The rearrangement seen in the de2-7 EGFR results in a frameshift mature mRNA lacking 801 nucleotides spanning exons 2-7 (Wong et al. (1992) Proc. Natl. Acad. Sci. USA 89, 2965-9; Yamazaki et al. (1990) Jpn. J. Cancer Res. 81, 773-9; Yamazaki et al. (1988) Mol. Cell. Biol. 8, 1816-20; and Sugawa et al. (1990) Proc. Natl. Acad. Sci. USA 87, 8602-6). The corresponding EGFR protein has a 267 amino acid deletion comprising residues 6 to 273 of the extracellular domain and a novel glycine residue at the fusion junction (Sugawa et al., 1990).This elimination, along with the insertion of a glycine residue, produces a unique binding peptide at the elimination interface (Sugawa et al., 1990). EGFRvIII has been reported in several types of tumors including glioma, breast, lung, ovarian and prostate cancer (Wikstrand et al. (1997) Cancer Res. 57, 4130-40; Olapade-Olaopa et al. (2000) Br. J. Cancer. 82, 18694; Wikstrand, et al. (1995) Cancer Res. 55, 3140-8; Garcia de Palazzo et al. (1993) Cancer Res. 53, 3217-20). Although this truncated receptor does not bind to ligand, it has low constitutive activity and imparts a significant growth advantage to glioma cells grown as xenografts of tumors in atomic mice (Nishikawa et al. (1994) Proc. Natl. Acad. Sci. USA 91,772731) and has the ability to transform NIH3T3 cells (Batra et al. (1995) Cell Growth Differ. 6, 1251-9) and MCF-7 cells. The cellular mechanisms used by de2-7 EGFR in glioma cells are not fully defined but are reported to include a decrease in apoptosis (Nagane et al. (1996) Cancer Res.56, 5079-86) and a small improvement in proliferation (Nagane et al., 1996). Since the expression of this truncated receptor is restricted to tumor cells, it represents a very specific target for antibody therapy. Antibody-drug conjugates (ADCs) represent a new class of medications comprising an antibody conjugated to a cytotoxic drug via a chemical linker. The therapeutic concept of ADCs is to combine the binding capabilities of an antibody with those of a drug, where the antibody is used to target the drug to a tumor cell by binding to a target surface antigen. Consequently, there is still a need in the art for anti-EGFR and ADC antibodies that can be used for therapeutic purposes in cancer treatment. SUMMARY OF THE INVENTION In certain aspects, the present invention provides anti-EGFR antibodies and antibody-drug conjugates (ADCs) that bind specifically to EGFRvIII. In one embodiment, the invention features human epidermal growth factor receptor (anti-hEGFR) antibodies, or antigen-binding portions thereof, that bind to an epitope in the amino acid sequence CGADSYEMEEDGVRKC (SEQ ID NO: 45) or compete with a second anti-hEGFR antibody for binding to epidermal growth factor receptor variant III (EGFRvIII) (SEQ ID NO: 33) in a competitive binding assay, wherein the second anti-EGFR antibody comprises a heavy chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 1 and a light chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 5; that binds to EGFR(1-525) (SEQ ID NO: 47) with a dissociation constant (Kd) of approximately 1 x 10-6 M or less, as determined by surface plasmon resonance;and inhibits tumor growth in an in vivo human small cell lung carcinoma (NSCLC) xenograft assay with a tumor growth inhibition (TGI) percentage of at least approximately 50% relative to a human IgG antibody that is not EGFR-specific, wherein the human IgG antibody is administered in the NSCLC xenograft assay at the same dose and frequency as the anti-hEGFR antibody, or the antigen-binding portion thereof. In certain embodiments of the invention, the antibodies, or antigen-binding portions thereof, bind to EGFR (1-525) (SEQ ID NO: 47) with a Kd between approximately 1 x 10-6 M and approximately 1 x 10-10 M, determined by surface plasmon resonance. In other embodiments of the invention, the antibodies, or antigen-binding portions thereof, are bound to EGFR (1-525) (SEQ ID NO: 47) with a Kd between approximately 1 x 10-6 M and approximately 1 x 10-7 M, as determined by surface plasmon resonance. In certain embodiments, the antibodies, or antigen-binding portions thereof, of the invention bind to EGFRvIII (SEQ ID NO: 33) with a Kd of approximately 8.2 x 10⁻⁹ M or less, as determined by surface plasmon resonance. In other embodiments, the antibody, or antigen-binding portion thereof, binds to EGFRvIII (SEQ ID NO: 33) with a Kd between approximately 8.2 x 10⁻⁹ M and approximately 6.3 x 10⁻¹⁰ M, as determined by surface plasmon resonance. In some embodiments, the antibody, or antigen-binding portion thereof, binds to EGFRvIII (SEQ ID NO: 33) with a Kd between approximately 8.2 x 10⁻⁹ M and approximately 2.0 x 10⁻⁹ M, as determined by surface plasmon resonance. In still other embodiments of the invention, the antibodies, or antigen-binding portions thereof, inhibit tumor growth by at least approximately 60% in an in vivo assay of human small cell lung carcinoma (NSCLC) xenograft relative to the human IgG antibody that is not EGFR-specific. In certain embodiments, the invention features antibodies, or antigen-binding portions thereof, that inhibit tumor growth by at least approximately 70% in an in vivo xenograft assay. of human small cell lung carcinoma (NSCLC) in relation to a human IgG antibody that is not EGFR-specific. In certain embodiments, the antibodies, or antigen-binding portions thereof, inhibit tumor growth by at least approximately 80% in an in vivo assay of human small cell lung carcinoma (NSCLC) xenograft in relation to a human IgG antibody that is not EGFR-specific. In some embodiments, the antibodies, or antigen-binding portions thereof, comprise a heavy chain CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 12, a heavy chain CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 11, and a heavy chain CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 10; and a light chain CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 8, a light chain CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 7, and a light chain CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 6.In yet another embodiment, the antibodies, or antigen-binding portions thereof, comprise a variable region of the heavy chain comprising the amino acid sequence detailed in SEQ ID NO: 9, and a variable region of the light chain comprising the amino acid sequence detailed in SEQ ID NO: 5. In a further embodiment, the antibodies, or antigen-binding portions thereof, comprise a heavy chain comprising the. amino acid sequence detailed in SEQ ID NO: 15, and a light chain comprising the amino acid sequence detailed in SEQ ID NO: 13. The invention also includes, in certain embodiments, anti-hEGFR antibodies, or antigen-binding portions thereof, comprising a light chain CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 40, a light chain CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 39, and a light chain CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 38; and a heavy chain CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 37, a heavy chain CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 36, and a heavy chain CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 35. In certain embodiments, the invention features anti-hEGFR antibodies, or antigen-binding portions thereof, comprising a variable heavy chain region comprising an amino acid sequence selected from the group consisting of 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, and 78; and a variable light chain region comprising an amino acid sequence selected from the group consisting of 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, and 79. In other embodiments, the invention includes anti-hEGFR antibodies, or antigen-binding portions thereof, comprising a set of heavy chain CDRs (CDR1, CDR2, and CDR3) selected from the group consisting of SEQ ID Nos: 10, 11, and 12; SEQ ID Nos: 16, 17, and 18; SEQ ID NOs: 10, 11, and 19; SEQ ID NOs: 20, 11, and 12; SEQ ID NOs: 21, 3, and 22; SEQ ID NOs: 16, 17, and 19; SEQ ID NOs: 2, 3, and 4; SEQ ID NOs: 10, 3, and 12; SEQ ID Nos: 80, 11, and 18; SEQ ID NOs: 80, 3, and 18; SEQ ID NOs: 20, 3, and 12; SEQ ID Nos: 80, 11, and 12; and SEQ ID Nos: 81, 11, and 22; and a set of CDRs of the light chain (CDR1, CDR2, and CDR3) selected from the group consisting of SEQ ID NOs: 6, 7, and 8; SEQ ID NOs: 23, 24, and 25; SEQ ID NOs: 26, 27, and 28; SEQ ID NOs: 29, 30, and 31; SEQ ID NOs: 6, 7, and 84; SEQ ID NOs: 82, 83, and 31; and SEQ ID Nos: 82, 27, and 85, wherein the antibodies, or antigen-binding portions thereof, do not comprise the heavy chain CDR set of SEQ ID Nos: 2, 3, and 4, and the light chain CDR set of SEQ ID Nos: 6, 7, and 8. In some embodiments, the antibodies, or antigen-binding portions thereof, comprise a heavy chain constant region comprising the amino acid sequence detailed in SEQ ID No: 41 and / or a light chain constant region comprising the amino acid sequence detailed in SEQ ID No: 43. In some embodiments of the invention, the antibodies, or antigen-binding portions thereof, comprise a heavy-chain immunoglobulin constant domain selected from the group consisting of a human IgG constant domain, a human IgM constant domain, a human IgE constant domain, and a human IgA constant domain. In some embodiments, the IgG constant domain is selected from the group consisting of an IgG1 constant domain, an IgG2 constant domain, an IgG3 constant domain, and an IgG4 constant domain. In other embodiments, the antibody is a multispecific antibody. In other embodiments of the invention, the antibodies, or antigen-binding portions thereof, comprise a Fab, a Fab', an F(ab')2, an Fv, an Fv with disulfide bond, an scFv, a single-domain antibody, and a divalent antibody. In still other embodiments of the invention, the antibodies, or antigen-binding portions thereof, are conjugated with an imaging agent. In certain embodiments of the invention, the imaging agent is selected from the group consisting of a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and biotin. In other embodiments of the invention, the radiolabel is indium. In still other embodiments, the invention includes a pharmaceutical composition comprising the antibody, or antigen-binding portion thereof, and a pharmaceutically acceptable carrier. The invention also includes, in some embodiments, an antibody-drug conjugate (ADC) comprising the antibody, or antigen-binding portion thereof, described herein, conjugated to at least one drug. In certain embodiments, the antibody is an anti-human epidermal growth factor receptor (anti-hEGFR) antibody, or antigen-binding portion thereof, that binds to an epitope in the amino acid sequence CGADSYEMEEDGVRKC (SEQ ID NO: 45) or competes with a second anti-hEGFR antibody for binding to variant III epidermal growth factor receptor (EGFRvIII) (SEQ ID NO: 33) in a competitive binding assay, wherein the second anti-EGFR antibody comprises a heavy-chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 1 and a light chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 5; binds to EGFR(1-525) (SEQ ID NO: 47) with a dissociation constant (Kd) of approximately 1 x 10-6 M or less, as determined by surface plasmon resonance; and inhibits tumor growth in an in vivo human small cell lung carcinoma (NSCLC) xenograft assay with a tumor growth inhibition (TGI%) of at least approximately 50% relative to a human IgG antibody that is not EGFR-specific, wherein the human IgG antibody is administered in the NSCLC xenograft assay at the same dose and frequency as the anti-hEGFR antibody, or antigen-binding portion thereof.In one embodiment of the invention, at least one drug is selected from the group consisting of an anti-apoptotic agent, a mitotic inhibitor, an anti-tumor antibiotic, an immunomodulatory agent, a nucleic acid for gene therapy, an alkylating agent, an anti-angiogenic agent, an antimetabolite, a boron-containing agent, a chemoprotective agent, a hormonal agent, an anti-hormonal agent, a corticosteroid, a photoactive therapeutic agent, an oligonucleotide, a radionuclide, a radiosensitizer, a topoisomerase inhibitor, and a tyrosine kinase inhibitor. In certain embodiments, the mitotic inhibitor is a dolastatin, an auristatin, a maitansinoid, and a plant alkaloid. An example of an auristatin is monomethylaustatin F (MMAF) or monomethylaustatin E (MMAE). Examples of maitansinoids include, but are not limited to, DM1, DM2, DM3, and DM4.In certain embodiments, the anti-tumor antibiotic is selected from the group consisting of an actinomycin, an anthracycline, and a... caliqueamycin, and a duocarmycin. In certain embodiments, actinomycin is a pyrrolobenzodiazepine (PBD). In still other embodiments, the invention includes a pharmaceutical composition comprising a mixture of ADCs comprising a plurality of the ADCs described herein, and a pharmaceutically acceptable carrier. In certain embodiments, the ADC mixture has an average drug-to-antibody ratio (DAR) of between 2 and 4. In other embodiments, the ADC mixture comprises ADCs wherein each has a DAR of between 2 and 8. In certain embodiments, the ADC mixture has an average drug-to-antibody ratio (DAR) of approximately between 2.4 and approximately 3.6. In certain embodiments, the invention includes methods for treating a subject suffering from cancer, comprising administering the pharmaceutical composition described herein to the subject, such that the subject suffering from cancer is treated. In one embodiment, the cancer is selected from the group consisting of breast cancer, lung cancer, glioblastoma, prostate cancer, pancreatic cancer, colon cancer, head and neck cancer, and kidney cancer. In one embodiment, the cancer is breast cancer. In one embodiment, the cancer is lung cancer.In one form of realization, cancer is prostate cancer. In one form of realization, the. Cancer is pancreatic cancer. In one embodiment, cancer is colon cancer. In one embodiment, cancer is head and neck cancer. In one embodiment, cancer is kidney cancer. In one embodiment, cancer is colorectal cancer. In one embodiment, cancer is mesothelioma. In one embodiment, cancer is squamous cell carcinoma. In one embodiment, cancer is triple-negative breast cancer. In one embodiment, cancer is non-small cell lung cancer. In certain embodiments, squamous cell carcinoma is squamous cell carcinoma of the lung or squamous cell carcinoma of the head and neck. In yet another embodiment, the cancer contains EGFR amplifications or overexpresses EGFR. In certain embodiments, the cancer is characterized by EGFR overexpression. In certain embodiments, the cancer is characterized by EGFR amplification. The invention further includes, in certain embodiments, methods for inhibiting or reducing the growth of a solid tumor in a subject having a solid tumor, comprising administering the pharmaceutical composition described herein to the subject suffering from the solid tumor, such that the growth of the tumor is inhibited or reduced. In certain embodiments, the solid tumor is characterized by having EGFR overexpression. In certain embodiments, the solid tumor is characterized by having EGFR amplification. In one embodiment of the invention, the invention provides methods for inhibiting or reducing the growth of a solid tumor in a subject having a solid tumor, comprising administering to the subject having the solid tumor a effective amount of the antibody or ADC described herein, such that the growth of the solid tumor is inhibited or reduced. In certain embodiments, the solid tumor is an EGFR-expressing solid tumor or an EGFRvIII-positive solid tumor. In other embodiments, the solid tumor is a non-small cell lung carcinoma or a glioblastoma. In still other embodiments, the solid tumor is a squamous cell carcinoma. In certain embodiments, the invention includes methods for treating a subject suffering from cancer, comprising administering the pharmaceutical composition described herein to the subject in combination with an additional agent or additional therapy. In certain embodiments, the additional agent is selected from the group consisting of an anti-PD1 antibody (e.g., pembrolizumab (Keytruda®) or nivolumab), an anti-CTLA-4 antibody (e.g., ipilimumab), ibrutinib, duvelisib, idelalisib, venetoclax, and temozolomide. In certain embodiments, the additional therapy is radiation. In certain embodiments, the additional agent is an anti-PD1 antibody (e.g., pembrolizumab (Keytruda®) or nivolumab). In certain embodiments, the additional agent is an anti-CTLA-4 antibody (e.g., ipilimumab). In certain embodiments, the additional agent is ibrutinib.In certain formulations, the additional agent is duvelisib. In certain formulations, the additional agent is idelalisib. In certain formulations, the additional agent is venetoclax. In certain formulations, the additional agent is temozolomide. The invention also provides, in certain embodiments, isolated nucleic acids encoding for antibodies, or binding portions to antigens thereof, such as those described herein. Furthermore, the invention includes a vector comprising the nucleic acid, and a host cell, for example, a prokaryotic or eukaryotic cell (for example, an animal cell, a protist cell, a plant cell, and a fungal cell) comprising the vector. In one embodiment of the invention, the animal cell is selected from the group consisting of a mammalian cell, an insect cell, and an avian cell. In another embodiment, the mammalian cell is selected from the group consisting of a CHO cell, a COS cell, and an Sp2 / 0 cell. In certain embodiments, the invention features anti-hEGFR antibody-drug conjugates (ADCs) comprising an anti-hEGFR antibody conjugated to an auristatin, wherein the antibody comprises a heavy chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 12, a heavy chain CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a heavy chain CDR1 domain comprising the amino acid sequence of SEQ ID NO: 10; and a light chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR2 domain comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR1 domain comprising the amino acid sequence of SEQ ID NO: 6.In one embodiment, the antibody comprises a heavy chain variable region comprising the amino acid sequence detailed in SEQ ID NO: 9, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 5. In yet another embodiment, the antibody comprises a domain. IgG heavy chain immunoglobulin constant. In yet another embodiment, IgG is an immunoglobulin heavy chain constant domain of IgG1 or IgG4. In one embodiment, the invention includes an ADC, wherein the auristatin is monomethylauristatin F (MMAF) or monomethylauristatin E (MMAE). In a further embodiment, the invention includes a heavy chain comprising the amino acid sequence of SEQ ID NO: 15, and comprises a light chain comprising the amino acid sequence of SEQ ID NO: 13. In yet another embodiment of the invention, the anti-EGFR antibody is covalently linked to aurstatin by a connector comprising maleimidocaproyl, valine-citrulline, p-aminobenzyl alcohol (mc-vc-PABA). In one embodiment, the invention includes an ADC comprising an anti-EGFR and a radio marker, for example Indian. In one embodiment, an anti-EGFR antibody described herein is covalently linked to at least one pyrrolobenzodiazepine (PBD). In certain embodiments, the anti-EGFR antibody described herein is linked to a PBD as described in Figure 21 (i.e., SGD-1882). In some embodiments, the invention comprises pharmaceutical compositions comprising the ADC described herein and a pharmaceutically acceptable carrier. In certain embodiments, the The invention presents pharmaceutical compositions comprising an ADC mixture comprising the ADC described herein, wherein the range of the average drug-to-antibody ratio (ADR) in the ADC mixture is between 2 and 4. In certain embodiments, the average drug-to-antibody ratio (ADR) in the ADC mixture is between 2.4 and 3.6. In one embodiment, the invention features pharmaceutical compositions comprising an ADC mixture comprising anti-hEGFR antibody-drug conjugates (ADC), and a pharmaceutically acceptable carrier, wherein the ADC mixture has an average drug-to-antibody ratio (DAR) between 2 and 4, and wherein said ADC comprises monomethylaustatin E (MMAE) conjugated to an anti-hEGFR antibody comprising a heavy-chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 12, a heavy-chain CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a heavy-chain CDR1 domain comprising the amino acid sequence of SEQ ID NO: 10;and a light chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR2 domain comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR1 domain comprising the amino acid sequence of SEQ ID NO: 6.; In one embodiment, the variable region of the antibody heavy chain comprises the amino acid sequence detailed in SEQ ID NO: 9, and the variable region of the anti-EGFR antibody light chain comprises the amino acid sequence detailed in SEQ ID NO: 5. In other embodiments of the invention, the antibody comprises an IgG heavy chain immunoglobulin constant domain. In other embodiments, the invention includes an antibody having an IgG1 or IgG4 heavy chain immunoglobulin constant domain. In one embodiment, the invention includes an antibody of the IgG1 isotype. In yet another embodiment, the invention includes antibodies comprising a heavy chain comprising the amino acid sequence detailed in SEQ ID NO: 15, and a light chain comprising the amino acid sequence of SEQ ID NO: 13. In one embodiment, the invention features an MMAE that is conjugated to the antibody by a connector comprising maleimidocaproyl, val-cyt, PABA. In one embodiment of the invention, the invention provides methods for treating a subject suffering from cancer, comprising administering a pharmaceutical composition comprising an antibody or ADC described herein to the subject, such that the subject suffering from cancer is treated. In one embodiment, the cancer is selected from the group consisting of breast cancer, lung cancer, glioblastoma, prostate cancer, pancreatic cancer, colon cancer, head and neck cancer, and kidney cancer. In yet another form of realization, the cancer contains amplifications of EGFR or overexpresses EGFR.In one form of realization, cell carcinoma. Squamous cell carcinoma is squamous cell carcinoma of the lung or squamous cell carcinoma of the head and neck. In one embodiment, the cancer is an EGFR-overexpressing cancer. In one embodiment, the cancer is characterized as EGFR-amplified. In one embodiment, the cancer is breast cancer. In one embodiment, the cancer is lung cancer. In one embodiment, the cancer is prostate cancer. In one embodiment, the cancer is pancreatic cancer. In one embodiment, the cancer is colon cancer. In one embodiment, the cancer is head and neck cancer. In one embodiment, the cancer is kidney cancer. In one embodiment, the cancer is colorectal cancer. In one embodiment, the cancer is mesothelioma. In one embodiment, the cancer is squamous cell carcinoma. In one embodiment, the cancer is triple-negative breast cancer.In one embodiment, the cancer is non-small cell lung cancer. In certain embodiments, squamous cell carcinoma is squamous cell lung cancer or squamous cell carcinoma of the head and neck. Additionally, in certain embodiments, the invention provides methods for inhibiting or reducing the growth of a solid tumor in a subject having a solid tumor, wherein said method comprises administering the pharmaceutical composition described herein to the subject having a solid tumor, such that the growth of the solid tumor is inhibited or reduced. In one embodiment, the solid tumor is a non-small cell lung carcinoma or a glioblastoma. In yet another embodiment, the solid tumor is an EGFRvIII-positive tumor or an EGFR-expressing solid tumor. In yet another embodiment, the solid tumor is a solid tumor that It overexpresses EGFR. In yet another embodiment, the solid tumor is an EGFR-amplified tumor. In one embodiment, the solid tumor is a non-small cell lung carcinoma that has amplified EGFR. In one embodiment, the solid tumor is a non-small cell lung carcinoma that has EGFR overexpression. In one embodiment, the solid tumor is a glioblastoma that has amplified EGFR. In one embodiment, the solid tumor is a glioblastoma that overexpresses EGFR. In certain embodiments, the invention provides combination therapies whereby the pharmaceutical compositions described herein are administered to a subject in need (e.g., a subject suffering from cancer or a solid tumor). The pharmaceutical compositions described herein may be administered concurrently with, prior to, or following the administration of an additional agent or additional therapy. In certain embodiments, the additional agent is selected from the group consisting of an anti-PD1 antibody, an anti-CTLA-4 antibody, temozolomide, a bcl-xl inhibitor, and a nicotinamide adenine phosphoribosyltransferase (NAMPT) inhibitor. In still other embodiments, the additional agent is a chemotherapeutic agent. In certain embodiments, the additional therapy is radiation. In other embodiments, the additional agent is ibrutinib (Imbruvica®, Pharmacyclics). In still other embodiments, the additional agent is duvelisib.In other embodiments, the additional agent is idelalisib (Zydelig®, Gilead Sciences, Inc.). In other embodiments, the additional agent is venetoclax (ABT-199 / GDC-0199, AbbVie, Inc.). In certain embodiments, the additional agent is an anti-PD1 antibody (e.g., pembrolizumab (Keytruda®) or nivolumab). In certain embodiments, the additional agent is a. anti-CTLA-4 antibody (e.g., ipilimumab). In certain formulations, the additional agent is temozolomide. In certain embodiments, the invention features a chimeric antigen receptor (CAR) comprising antigen-binding regions, for example CDRs, of the antibodies described herein or a scFv described herein. In certain embodiments, the invention features a CAR comprising a light-chain variable region comprising a CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 40, a CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 39, and a CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 38; and a heavy-chain variable region comprising a CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 37, a CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 36, and a CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 35. In certain embodiments, the invention features a CAR comprising a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 12, a CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 10; and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 8, a CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 7, and a CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 6. Brief description of the figures Figure 1 provides the amino acid sequences of the variable heavy chain (VH) and variable light chain (VL) regions of Ab1 (SEQ ID NOs: 1 and 5) and AbA (SEQ ID NOs: 9 and 5). The CDR sequences in the VH and VL regions are boxed, and the differences between the Ab1 VH sequence and the AbA VH sequence are shaded. Figure 2 describes the full-length light and heavy chain sequences for Ab1 (SEQ ID NOs: 13 and 14) and AbA (SEQ ID NOs: 13 and 15). The differences between the Ab1 and AbA sequences in the heavy chain are highlighted. Figure 3 provides a table summarizing the affinity measurements of the Biacore binding assay for multiple Ab1 variant antibodies compared to Ab1 and Ab2. EGFR(1-525) and EGFRvIII were used in the binding analysis. ka(M-1 s-1) as described in Figure 3 refers to the rate constant for the association of an antibody to the antigen to form the antibody / antigen complex, kd(s-1) refers to the rate constant for the dissociation of an antibody from the antibody / antigen complex, and kd(M) refers to the dissociation rate constant. Figure 4 provides a graphical summary of a FACS analysis showing that AbA had increased binding to A431 tumor cells (human squamous cell carcinoma cells) compared to Ab1, but lower binding affinity compared to Ab2. Figure 5 describes the results of a competition assay by FACS indicating that Ab1 variant antibodies recognize the same EGFR epitope as Ab1. Figure 6 provides a summary of the binding of Ab1 and Ab1 variant antibodies to EGFR (1-525). Filled circles represent Ab1 or Ab2 (controls), and open circles represent Ab1 variant antibodies. The circles indicate Group 1 and Group 2, summarizing the data provided in Figure 7. Figure 7 presents Western blot analysis results examining the activity of Ab1 and Ab1 variant antibodies in different cell lines in vitro. SCC-15 cells (Figure 7A) and H292 cells were exposed to conditions as described in Example 4 and analyzed using Western blot analysis with anti-EGFR (pY EGFR), anti-EGFR (total EGFR), and anti-actin antibodies. Figure 7A shows the ability of Ab1, Ab2, and Ab1 variant antibodies to inhibit EGF-mediated tyrosine phosphorylation of EGFR in SCC-15 cells. Figure 7B provides results showing the ability of Ab1, Ab2, and Ab1 variant antibodies to inhibit EGF-mediated tyrosine phosphorylation of EGFR in H292 cells. Figure 8 graphically describes the results of ELISA assays for pEGFR including Ab1, Ab2 and Ab1 variants (Figure 8A) and the level of inhibition of Ab1 compared to Ab2 and AbP (Figure 8B) from the A431 inhibition study. The Y-axis in Figure 8A is the optical density (OD) at 450 nm. Figure 9 graphically describes the binding of Ab1, Ab2, and Ab1 variant antibodies to normal human epidermal keratinocytes expressing wild-type EGFR using the FACS binding assay. Figure 10 graphically describes the results of a mouse xenograft inhibition assay comparing the ability of AbA, AbG, AbK, AbM and AbP were tested to inhibit tumor growth in a human NSCLC carcinoma xenograft compared to Ab1, Ab2, and a human IgG (huIgG) control. Arrows indicate the time points for administration of the different antibodies. Figure 11 provides the structure of the AbA-malemidocaproyl-vc-PABA-MMAE ADC (referred to herein as “AbA-vcMMAE”). Figures 12-1 and 12-2 provide results of the hydrophobic interaction chromatography (HIC) analysis of the AbA-vcMMAE purification. Figures 13-1 and 13-2 provide results of the size exclusion chromatography (SEC) analysis of AbA-vcMMAE. Figure 14 graphically describes the results of two mouse xenograft inhibition assays using anti-EGFR ADCs. Figure 14A describes the results of a mouse xenograft inhibition assay comparing tumor growth inhibition in NCI-H1703 cells from a human NSCLC carcinoma xenograft, demonstrating increased inhibition by AbA-vcMMAE compared to Ab1 and an Ab1-mcMMAF ADC. Figure 14B describes the results of a mouse xenograft inhibition assay comparing tumor growth inhibition in EBC-1 cells from a human NSCLC carcinoma xenograft, demonstrating increased inhibition by AbA-vcMMAE compared to Ab1 and an Ab1-mcMMAF ADC. The arrows indicate the points in time following antibody administration. Figure 15 graphically describes the results of mouse xenograft inhibition assays using anti-EGFR ADCs. Figure 15A shows results from a mouse xenograft inhibition assay comparing the inhibition of tumor growth in NCI-H292 cells that demonstrates increased inhibition by AbA-vcMMAE (AbA-vcMMAEp) and purified AbA-vcMMAE compared to purified Abl-vcMMAE (Ab1-vcMMAEp), Ab1-vcMMAE, ADC, purified Ab1-mcMMAF (Ab1-mcMMAFp), and Ab1-mcMMAF (versus three controls). Figure 15B shows results from a mouse xenograft inhibition assay comparing tumor growth inhibition in NCI-H292 cells, demonstrating increased inhibitory activity of AbA-vcMMAE compared to purified AbA-vcMMAE (AbA-vcMMAEp) and AbA-vcMMAE compared to purified Ab1-vcMMAE (Ab1-vcMMAEp), Ab1-vcMMAE, Ab1-mcMMAF, and Ab1-mcMMAFp. The doses of the molecules in Figures 15A and B are indicated in parentheses, i.e., 3 mg / kg or 6 mg / kg. The arrows indicate the points in time for antibody or ADC administration. Control 2 in Figure 15 represents a negative control, which is an anti-tetanus toxin antibody that does not bind to EGFR. Figure 16 provides the amino acid sequences of the variant Ab1 variable heavy chain (VH) library design (Figure 16A) and the variant Ab1 variable light chain (VL) library design (Figure 16B). Figure 17 shows a schematic of EGFR and the regions attached to Ab1 and Ab2. Figure 18 graphically describes the results of xenograft inhibition assays in mice (using NCI-H292 cells (NSCLC)) using anti-EGFR ADCs. The doses of the molecules are indicated in parentheses, i.e., 3 mg / kg or 6 mg / kg. The arrows indicate the points in time for antibody or ADC administration. Figure 19 graphically describes the results of a mouse glioblastoma xenograft inhibition assay using anti-EGFR ADCs MMAE and MMAF. The doses of the molecules in Figure 19 are indicated in parentheses, i.e., 1 mg / kg. The arrows indicate the points in time for antibody or ADC administration. Control 2 in Figure 19 represents a negative control, which is an anti-tetanus toxin antibody that does not bind to EGFR. Figures 20A and B graphically describe the results of a single-photon emission computed tomography (SPECT) imaging assay comparing the effectiveness of antibody uptake by EGFR-expressing tumors in two tumor models (SW48 tumor models (Figure 20A) and EBC1 (Figure 20B), respectively) using an AbA, Ab1 antibody, or a 111In-labeled control. Figure 21 describes the structure of a PBD dimer (SGD-1882) conjugated to an antibody (Ab) by means of a maleimidocaproyl-valine-alanine connector (collectively referred to as SGD-1910). DETAILED DESCRIPTION OF THE INVENTION Different aspects of the invention relate to anti-EGFR antibodies and antibody fragments, anti-EGFR ADCs, and pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors, and host cells for making such antibodies and fragments. The invention also encompasses methods for using the antibodies and ADCs described herein to detect human EGFR, to inhibit human EGFR activity (in vitro or in vivo), and to treat cancers such as epithelial cancers, including breast cancer, colorectal cancer, head and neck cancers (e.g., glioblastomas), lung cancer, kidney cancer, pancreatic cancer, mesothelioma, and squamous cell carcinoma (e.g., squamous cell carcinoma of the lung or squamous cell carcinoma of the head and neck). triple-negative breast cancer, non-small cell lung cancer, and prostate cancer. I. Definitions To facilitate understanding of the invention, certain terms are first defined. Additionally, it should be noted that whenever a value or range of values ​​for a parameter is specified, the intermediate values ​​and ranges of those values ​​are also intended to be part of this invention. The terms “anti-epidermal growth factor receptor (EGF) antibody” or “anti-EGFR antibody,” used synonymously herein, refer to an antibody that binds specifically to EGFR. An antibody that binds to an antigen of interest, i.e., EGFR, is one that has the ability to bind that antigen with sufficient affinity that the antibody is useful for targeting a cell that expresses the antigen. In a preferred embodiment, the antibody binds specifically to human EGFR (hEGFR). Examples of anti-EGFR antibodies are described in Example 1 below. Unless otherwise stated, the term “anti-EGFR antibody” is intended to refer to an antibody that binds to wild-type EGFR or any variant of EGFR, such as EGFRvIII. The amino acid sequence of wild-type human EGFR is provided below as SEQ ID NO: 32, wherein the signal peptide (amino acid residues 1-24) is underlined, and the amino acid residues of the extracellular domain (ECD, amino acid residues 25-645) are highlighted in bold. A truncated wild-type ECD of EGFR (also referred to herein as EGFR(1-525)) corresponds to SEQ ID NO: 47 and is equivalent to the amino acids 1-525 of SEQ ID NO: 32. The mature form of wild-type EGFR corresponds to the protein without the signal peptide, i.e., amino acid residues 25 to 1210 of SEQ ID NO: 32. 1 mrpsgtagaa llallaalcp asraleekkv cqgtsnkltq Igtfedhfls Iqrmfnncev 61 vlgnleityv qrnydlsflk tiqevagyvl ialntverip lenlqiirgn myyensyala 121 vlsnydankt glkelpmrnl qeilhgavrf snnpalcnve siqwrdivss dflsnmsmdf 181 qnhlgscqkc dpscpngscw gageencqkl tkiicaqqcs grcrgkspsd cchnqcaagc 241 tgpresdclv crkfrdeatc kdtcpplmly npttyqmdvn pegkysfgat cvkkcprnyv 301 vtdhgscvra cgadsyemee dgvrkckkce gpcrkvcngi gigefkdsls inatnikhfk 361 nctsisgdlh ilpvafrgds fthtppldpq eldilktvke itgflliqaw penrtdlhaf 421 enleiirgrt kqhgqfslav vslnitslgl rslkeisdgd viisgnknlc yantinwkkl 481 fgtsgqktki isnrgensck atgqvchalc spegcwgpep rdcvscrnvs rgrecvdkcn 541 llegeprefv enseciqchp eclpqamnit ctgrgpdnci qcahyidgph cvktcpagvm 601 genntlvwky adaghvchlc hpnctygctg pglegcptng pkipsiatgm vgalllllvv 661 algiglfmrr rhivrkrtlr rllqerelve pltpsgeapn qallrilket efkkikvlgs 721 gafgtvykgl wipegekvki pvaikelrea tspkankeil deayvmasvd nphvcrllgi 781 cltstvqlit qlmpfgclld yvrehkdnig sqyllnwcvq iakgmnyled rrlvhrdlaa 841 rnvlvktpqh vkitdfglak llgaeekeyh aeggkvpikw malesilhri ythqsdvwsy 901 gvtvwelmtf gskpydgipa seissilekg erlpqppict idvymimvkc wmidadsrpk 961 freliiefsk mardpqrylv iqgdermhlp sptdsnfyra lmdeedmddv vdadeylipq 1021 qgffsspsts rtpllsslsa tsnnstvaci drnglqscpi kedsflqrys sdptgalted 1081 siddtflpvp eyinqsvpkr pagsvqnpvy hnqplnpaps rdphyqdphs tavgnpeyln 1141 tvqptcvnst fdspahwaqk gshqisldnp dyqqdffpke akpngifkgs taenaeylrv 1201 apqssefiga (SEQ ID NO: 32) The amino acid secuencia of the ECD and EGFR humano se provee mas adelante como SEQ ID NO: 34, and include the secuencia senal (subrayado). 1 mrpsgtagaa llallaalcp asraleekkv cqgtsnkltq Igtfedhfls Iqrmfnncev 61 vlgnleityv qrnydlsflk tiqevagyvl ialntverip lenlqiirgn myyensyala 121 vlsnydankt glkelpmrnl qeilhgavrf snnnpalcnve siqwrdivss dflsnmsmdf 181 qnhlgscqkc dpscpngscw gageencqkl tkiicaqqcs grcrgkspsd cchnqcaagc 241 tgpresdclv crkfrdeatc kdtcpplmly npttyqmdvn pegkysfgat cvkkcprnyv 301 vtdhgscvra cgadsyemee dgvrkckkce gpcrkvcngi gigefkdsls inatnikhfk 361 nctsisgdlh ilpvafrgds fthtppldpq eldilktvke itgflliqaw penrtdlhaf 421 enleiirgrt kqhgqfslav vslnitslgl rslkeisdgd viisgnknlc yantinwkkl 481 fgtsgqktki isnrgensck atgqvchalc spegcwgpep rdcvscrnvs rgrecvdkcn 541 llegeprefv enseciqchp eclpqamnit ctgrgpdnci qcahyidgph cvktcpagvm 601 genntlvwky adaghvchlc hpnctygctg pglegcptng pkips (SEQ ID NO: 34) The complete structure of EGFR is described in Figure 17. The EGFR ECD has four domains (Cochran et al. (2004) J. Immunol. Methods 287, 147-158). Domains I and III have been suggested to contribute to the formation of high-affinity ligand-binding sites. Domains II and IV are cysteine-rich, laminin-like regions that stabilize protein folding and contain a possible EGFR dimerization interface. EGFR variants can result from gene rearrangement accompanied by amplification of the EGFR gene. EGFRvIII is the most common naturally occurring variant of EGFR in human cancers (Kuan et al. Endocr Relat Cancer. 8(2):83-96 (2001)). During gene amplification, a deletion of 267 amino acids occurs in the extracellular domain of EGFR, resulting in the loss of a glycine residue. inserted at the fusion junction. Therefore, EGFRvIII lacks amino acids 6-273 of the extracellular domain of wild-type EGFR and includes an insertion of a glycine residue at the junction. The EGFRvIII variant of EGFR contains a deletion of 267 amino acid residues in the extracellular domain where a glycine is inserted at the deletion junction. The amino acid sequence of EGFRvIII is shown below as SEQ ID NO: 33 (the ECD is highlighted in bold and corresponds to SEQ ID NO: 46, the signal sequence is underlined). mrpsgtagaalallaalcpasraleekkgnyvvtdhgscvracgadsyemeedgvrkckkcegpcr kvcngigigefkdslsinatnikhfknctsisgdlhilpvafrgdsfthtppldpqeldilktvkeitgflliq awpenrtdlhafenleiirgrtkqhgqfslavvslnitslglrslkeisdgdviisgnknlcyantinwkkl fgtsgqktkiisnrgensckatgqvchalcspegcwgpeprdcvscrnvsrgrecvdkcnllegepr efvenseciqchpeclpqamnitctgrgpdnciqcahyidgphcvktcpagvmgenntlvwkyad aghvchlchpnctygctgpglegcptngpkipsiatgmvgalllllvvalgiglfmrrrhivrkrtlrrllqerelv epltpsgeapnqallrilketefkkikvlgsgafgtvykglwipegekvkipvaikelreatspkankeildeayvm asvdnphvcrllgicltstvqlitqlmpfgclldyvrehkdnigsqyllnwcvqiakgmnyledrrlvhrdlaarnvlv ktpqhvkitdfglakllgaeekeyhaeggkvpikwmalesilhriythqsdvwsygvtvwelmtfgskpydgip aseissilekgerlpqppictidvymimvkcwmidadsrpkfreliiefskmardpqrylviqgdermhlpsptd snfyralmdeedmddvvdadeylipqqgffsspstsrtpllsslsatsnnstvacidrnglqscpikedsflqrys sdptgaltedsiddtflpvpeyinqsvpkrpagsvqnpvyhnqplnpapsrdphyqdphstavgnpeylntv qptcvnstfdspahwaqkgshqisldnpdyqqdffpkeakpngifkgstaenaeylrvapqssefiga (SEQ ID NO: 33) EGFRvIII contributes to tumor progression through constitutive signaling in a ligand-independent manner. EGFRvIII expression is unknown in normal tissues (Wikstrand et al. Cancer Research). 55(14): 3140-3148 (1995); Olapade-Olaopa et al. Br J Cancer. 82(1):186-94 (2000)), but shows significant expression in tumor cells, including breast cancers, gliomas, NSCL cancers, ovarian cancers, and prostate cancers (Wikstrand et al. Cancer Research 55(14): 3140-3148 (1995); Ge et al. Int J Cancer. 98(3):357-61 (2002); Wikstrand et al. Cancer Research 55(14): 3140-3148 (1995); Moscatello et al. Cancer Res. 55(23):5536-9 (1995); Garcia de Palazzo et al. Cancer Res. 53(14):3217-20 (1993); Moscatello et al. Cancer Res. 55(23):5536-9 (1995); and Olaopa-Olaopa et al. 2(1):186-94 (2000)). “Biological activity of EGFR” as used herein, refers to all the inherent biological properties of EGFR, which include, but are not limited to, binding to epidermal growth factor (EGF), binding to tumor growth factor alpha (TGFA), homodimerization, activation of JAK2 kinase activity, activation of MAPK kinase activity, and activation of transmembrane receptor protein tyrosine kinase activity. The terms “specific binding” or “specifically bound,” as used herein, in reference to the interaction of an antibody or ADC with a second chemical species, mean that the interaction depends on the presence of a particular structure (e.g., an antigenic determinant or epitope) on the chemical species; for example, an antibody recognizes and binds to a specific protein structure rather than to proteins in general. If an antibody or ADC is specific for an epitope “A,” the presence of a molecule containing epitope A (or free, unlabeled A) in a reaction containing “A” labeled and the antibody, will reduce the amount of labeled A bound to the antibody or ADC. The phrase “specifically binds to hEGFR” or “specifically bound to hEGFR”, as used herein, refers to the ability of an anti-EGFR antibody or ADC to interact with hEGFR with an affinity equal to or greater than that of Ab1 or an Ab1 ADC. The term “specifically binds to EGFR(1-525)” or “specifically binds to EGFR(1-525)”, as used herein, refers to an antibody or ADC that binds to EGFR(1-525) and has a dissociation constant (Kd) of 2.3 x 10-6 M or less, as determined by surface plasmon resonance. The term “antibody” generally refers to any immunoglobulin (Ig) molecule composed of four polypeptide chains—two heavy chains (H) and two light chains (L)—or any functional fragment, mutant, variant, or derivative thereof, that retains the essential epitope-binding characteristics of an Ig molecule. These mutant, variant, or derivative antibody formats are known in the art. Non-limiting embodiments of these formats will be described below. In a complete antibody, each heavy chain is composed of a heavy chain variable region (abbreviated HCVR or VH herein) and a heavy chain constant region. The heavy chain constant region is composed of three domains: CH1, CH2, and CH3. Each light chain is composed of a light chain variable region (abbreviated LCVR or VL herein) and a light chain constant region. The light chain constant region consists of a CL domain. The VH and VL regions can be further divided into hypervariable regions, known as Complementarity determination regions (CDRs) are separated by conserved regions known as scaffolding regions (FRs). Each VH and VL is composed of three CDRs and four FRs, arranged from the amino-terminal end to the carboxy-terminal end in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. Immunoglobulin molecules can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY) and class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2) or subclass. The term “antigen-binding portion” of an antibody (or simply “antibody portion”), as used herein, refers to one or more fragments of an antibody that retain the ability to bind specifically to an antigen (e.g., hIL-13). It has been shown that the antigen-binding function of an antibody can be carried out by fragments of a full-length antibody. These forms of antibody embodiment can also be bispecific, with dual specificity, or multispecific, meaning they can bind specifically to two or more different antigens.Examples of binding fragments encompassed by the term “antigen-binding portion” of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL, and CH1 domains; (ii) an F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked together at the hinge region via a disulfide bond; (iii) an Fd fragment, consisting of the VH and CH1 domains; (iv) an Fv fragment, consisting of the FL and VH domains of a single antibody arm; (v) a dAb fragment (Ward et al., (1989) Nature 341:544-546, Winter et al., PCT Publication WO 90 / 05144, incorporated herein by reference), consisting of a VH domain; and (vi) a determinant region. Isolated complementarity (CDR). Furthermore, although the two domains of the Fv fragment, namely VL and VH, are encoded by separate genes, they can be connected to each other using a synthetic connector that allows them to be prepared as a single protein chain, where the VL and VH regions pair to form monovalent molecules (known as single-chain Fv (scFv); see, for example, Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85: 5879-5883). Such single-chain antibodies are also considered within the term “antigen-binding portion” of an antibody. In certain embodiments of the invention, the scFv molecules can be incorporated into a fusion protein. Other forms of antibodies are also included, such as divalent antibodies.Divalent antibodies are bivalent and bispecific antibodies in which the VH and VL domains are expressed on a single polypeptide chain, but using a linker that is too short for the two domains to combine on the same chain, thus forcing the pairing of these domains with complementary domains of a different chain and the formation of two antigen-binding sites (see, for example, Holliger, P., et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak, RJ, et al. (1994) Structure 2:1121-1123). These antibody-binding portions are well known in the art (Kontermann and Dubel, editors, Antibody Engineering (2001) Springer-Verlag. New York. 790 pages (ISBN 3-540-41354-5). The term “antibody construct,” as used herein, refers to a polypeptide comprising one or more antigen-binding portions of the invention, linked to a connector polypeptide or an immunoglobulin constant domain. The connector polypeptides comprise Two or more amino acid residues linked by peptide bonds are used to connect one or more antigen-binding portions. These linking polypeptides are well known in the art (see, for example, Holliger, P., et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak, RJ, et al. (1994) Structure 2:1121-1123). An immunoglobulin constant domain refers to a constant domain of a heavy or light chain. Example amino acid sequences of the heavy and light chain constant domains of human IgG are known in the art and are represented below. Sequences of constant domains of the weighing cycle and constant domains of the Livian cycle of human IgG Prote^na Identificado r de secuencia Security 12345678901234567890123456789 012 Region constante de Ig gamma-1 SEQ ID N° 41 ASTKGPSVFPLAPSSKSTSGGTAA LGCLVKDYFPEPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVP SSSLGTQTYICNVNHKPSNTKVDK KVEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVM HEALHNHYTQKSLSLSPGK Prote^na Identificado r de secuencia Security 12345678901234567890123456789 012 Constant mutant region of Ig gamma-1 SEQ ID N° 42 ASTKGPSVFPLAPSSKSTSGGTAA LGCLVKDYFPEPPVTVSWNSGALTS GVHTFPAVLQSSGLYSLSSVVTVP SSSLGTQTYICNVNHKPSNTKVDK KVEPKSCDKTHTCPPCPAPEAAG GPSVFLFPPKDTLMISRTPEVTC VVVDPEVVKFVVWGVWGVV HNACTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPI EKTISKKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQFSQGNVKVHKSLQSLQSL Ig kappa constant region SEQ ID No. 43 RTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREACVQWKVDNALQ SGNSQESVTEQDSKDSTYSLSSTL TLSKADYEKKVYACEVTHQGLSS PVTKSFNRGEC Protein Identified r of sequence Sequence 12345678901234567890123456789 012 Constant region of Ig Lambda SEQ ID No. 44 QPKAAPSVTLFPPSSEELQANKAT LVCLISDFYPGAVTVAWKADSSPV KAGVEI 1 IPSKQSNNKYAASSYLS LTPEQWKSHRSYSCQVTHEGSTV EKTVAPTECS Additionally, an antibody, or an antigen-binding portion thereof, may be part of a larger immunoadhesion molecule, formed by the covalent or non-covalent association of the antibody or antibody portion with one or more proteins or peptides. Examples of such immunoadhesion molecules include the use of the core region of streptavidin to prepare a tetrameric scFv molecule (Kipriyanov, SM, et al. (1995) Human Antibodies and Hybridomas 6:93-101) and the use of a cysteine ​​residue, a marker peptide, and a C-terminal polyhistidine tag to prepare bivalent, biotinylated scFv molecules (Kipriyanov, SM, et al. (1994) Mol. Immunol. 31:1047-1058). Portions of antibodies, such as the Fab and F(ab')2 fragments, can be prepared from whole antibodies using conventional techniques, such as digestion with papain or pepsin, respectively, of whole antibodies.Furthermore, antibodies, antibody fragments, and immunoadhesion molecules can be obtained. using recombinant DNA techniques, as described in this documentation. An “isolated antibody,” as used herein, is intended to refer to an antibody that is substantially free of other antibodies having different antigenic specificities (for example, an isolated antibody that binds specifically to EGFR is substantially free of antibodies that bind specifically to antigens other than EGFR). An isolated antibody that binds specifically to EGFR may, however, cross-react with other antigens, such as EGFR molecules from other species. Furthermore, an isolated antibody may be substantially free of other cellular material and / or chemicals. The term “humanized antibody” refers to antibodies comprising sequences from the variable region of the heavy and light chains of a non-human species (e.g., a mouse), but where at least a portion of the heavy and / or light chain sequence has been altered to be more “human-like,” that is, to be more similar to the variable sequences of the human germline. The term “humanized antibody” is an antibody, or a variant, derivative, analog, or fragment thereof, that binds immunospecifically to an antigen of interest, and that comprises a scaffold region (FR) substantially having the amino acid sequence of a human antibody and a complementarity-determining region (CDR) substantially having the amino acid sequence of a non-human antibody.As used herein, the term "substantially" in the context of a CDR refers to a CDR that has an amino acid sequence of at least 80%, preferably at least. 85%, at least 90%, at least 95%, at least 98%, or at least 99% identical to the amino acid sequence of a CDR of a non-human antibody. A substantially humanized antibody comprises all of at least one, and typically two, variable domains (Fab, Fab', F(ab')2, FabC, Fv), wherein all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin (i.e., the donor antibody), and all or substantially all of the scaffold regions are those of a human immunoglobulin consensus sequence. Preferably, a humanized antibody also comprises at least a portion of an immunoglobulin constant (Fc) region, typically that of a human immunoglobulin. In some embodiments, a humanized antibody contains the light chain and at least the variable domain of a heavy chain. The antibody may also include the CH1, hinge, CH2, CH3, and CH4 regions of the heavy chain.In some embodiments, a humanized antibody contains only a humanized light chain. In other embodiments, a humanized antibody contains only a humanized heavy chain. In specific embodiments, a humanized antibody contains only a humanized variable domain of a light chain and / or a humanized heavy chain. The humanized antibody can be selected from any immunoglobulin class, including IgM, IgG, IgD, IgA, and IgE, and any isotype, including, but not limited to, IgG1, IgG2, IgG3, and IgG4. The humanized antibody may comprise sequences from more than one class or isotype, and particular constant domains may be selected for the purpose of to optimize the desired effector functions using procedures well known in the art. The terms “Kabat numbering,” “Kabat definitions,” and “Kabat nomenclature” are used synonymously herein. These terms, which are recognized in the art, refer to a system for numbering amino acid residues that are more variable (i.e., hypervariable) than other amino acid residues in the variable regions of the heavy and light chains of an antibody or in an antigen-binding portion thereof (Kabat et al. (1971) Ann. NY Acad. Sci. 190:382–391, and Kabat, EA, et al. (1991) Sequences of Proteins of Immunological Interest, fifth edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242). For the variable region of the heavy chain, the hypervariable region extends between amino acid positions 31 and 35 for CDR1, between amino acid positions 50 and 65 for CDR2, and between amino acid positions 95 and 102 for CDR3.For the variable region of the light chain, the hypervariable region extends between amino acid positions 24 and 34 for CDR1, between amino acid positions 50 and 56 for CDR2, and between amino acid positions 89 and 97 for CDR3. As used herein, the term “CDR” refers to the complementarity-determining region within the variable sequences of an antibody. There are three CDRs in each variable region of the heavy chain (HC) and light chain (LC), designated CDR1, CDR2, and CDR3 (or specifically HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3), for each of the variable regions. The term “CDR set,” as used herein, refers to a group of three CDRs that appear in a single variable region and allow binding to the antigen. The exact limits of these CDRs have been defined in different terms according to different systems. The system described by Kabat (Kabat et al., Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987) and (1991)) not only provides an unambiguous numbering system for residues that can be applied to any variable region of an antibody, but also provides precise limits for the residues that define the three CDRs. These CDRs can be called Kabat CDRs. Chotia and colleagues (Chotia and Lesk, J. Mol. Biol. 196:901-917 (1987) and Chotia et al., Nature 342:877-883 (1989)) discovered that certain subportions within the Kabat CDRs adopt almost identical conformations of the peptide backbone, despite their great diversity at the amino acid sequence level.These subportions were designated L1, L2, and L3 or H1, H2, and H3, where “L” and “H” refer to the light chain and heavy chain regions, respectively. These regions can be called Chotia CDRs, and they have boundaries that overlap with Kabat CDRs. Other boundaries that define CDRs that overlap with Kabat CDRs have been described by Padlan (FASEB J. 9:133-139 (1995)) and MacCallum (J Mol Biol 262(5):732-45 (1996)). Other definitions of CDR limits may not be strictly consistent with the systems described above, but they may still overlap with Kabat's CDRs, although they may be shortened or lengthened in light of predictions or experimental findings that there are particular residues or groups of residues, or even entire CDRs, that do not significantly affect antigen binding. CDRs may be used in the methods described herein. defined according to any of these systems, although in preferred embodiments CDRs defined according to Kabat or Chotia are used. As used herein, the term “scaffolding” or “scaffolding sequence” refers to the remaining sequences of a variable region minus the CDRs. Because the exact definition of a CDR sequence can be determined using different systems, the meaning of a scaffolding sequence is subject to correspondingly different interpretations. The six CDRs (CDR-L1, CDR-L2, and CDR-L3 of the light chain and CDR-H1, CDR-H2, and CDR-H3 of the heavy chain) also divide the scaffolding regions into light and heavy chain with four subregions (FR1, FR2, FR3, and FR4) in each chain, where CDR1 is positioned between FR1 and FR2, CDR2 between FR2 and FR3, and CDR3 between FR3 and FR4. Without specifying particular subregions such as FR1, FR2, FR3 or FR4, a scaffolding region, as defined by others, represents the combined FRs in the variable region of a naturally occurring single immunoglobulin chain.As used herein, an FR represents one of the four subregions, and FRs represent two or more of the four subregions that constitute a scaffolding region. The scaffold and CDR regions of a humanized antibody need not precisely match the parental sequences; for example, the CDR of the donor antibody or consensus scaffold may have been mutated by the substitution, insertion, and / or deletion of at least one amino acid residue, such that the residue in the CDR or scaffold at that site does not match the donor antibody or consensus scaffold. However, in a preferred embodiment, these mutations are not extensive. Typically, they are at least 50, 55, 60, 65, 70, 75, or 80%, preferably at least 85%, more preferably at least 90%, and more preferably at least 95% of the residues of the humanized antibody shall correspond to those of the parental FR and CDR sequences. As used herein, the term “consensus scaffold” refers to the scaffold region in the consensus immunoglobulin sequence. As used herein, the term “consensus immunoglobulin sequence” refers to the sequence formed from the most frequently occurring amino acids (or nucleotides) in a family of related immunoglobulin sequences (see, for example, Winnaker, From Genes to Clones (Verlagsgesellschaft, Weinheim, Germany, 1987)). In an immunoglobulin family, each position in the consensus sequence is occupied by the amino acid that occurs most frequently at that position in the family. When two amino acids occur with equal frequency, either of them may be included in the consensus sequence. “Percentage (%) amino acid sequence identity” with respect to a peptide or polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in the specified peptide or polypeptide sequence, after aligning the sequences and introducing non-matches, if necessary, to achieve the maximum percentage of sequence identity, and without considering any conservative substitutions as part of the sequence identity. Alignment for the purpose of determining the percentage of amino acid sequence identity can be achieved in various ways that are within the realm of best practice, for example, using publicly available computer programs such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR). Experience in the art can determine appropriate parameters for measuring alignment, including algorithms required to achieve maximum alignment over the full length of the sequences being compared. In one embodiment, the invention includes an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with an amino acid sequence indicated in any of the SEQ ID Nos: 1 to 31, 35-40, or 50 to 85. The term “multivalent antibody” is used herein to indicate an antibody comprising two or more antigen-binding sites. In certain embodiments, the multivalent antibody may be designed to have three or more antigen-binding sites, and it is generally not a naturally occurring antibody. The term “multispecific antibody” refers to an antibody capable of binding to two or more unrelated antigens. In one embodiment, a multispecific antibody is a bispecific antibody capable of binding to two unrelated antigens; for example, a bispecific antibody, or its antigen-binding portion, that binds to EGFR (e.g., EGFRvIII) and CD3. The term “dual variable domain” or “DVD,” as used synonymously herein, refers to antigen-binding proteins that comprise two or more antigen-binding sites and are tetravalent or multivalent binding proteins. Such DVDs can be monospecific, meaning capable of binding one antigen, or multispecific, meaning capable of binding two or more antigens. DVD binding proteins comprising two DVD polypeptides A heavy chain and two light chain DVD polypeptides are known as an Ig DVD. Each half of an Ig DVD comprises a heavy chain DVD polypeptide, a light chain DVD polypeptide, and two antigen-binding sites. Each binding site comprises a heavy chain variable domain and a light chain variable domain, with a total of 6 CDRs participating in antigen binding per antigen-binding site. In one embodiment, the CDRs described herein are used in an anti-EGFR DVD. The term "chimeric antigen receptor" or "CAR" refers to a recombinant protein comprising at least (1) an antigen-binding region, e.g. a variable heavy or light chain of an antibody, (2) a transmembrane domain for anchoring the CAR to a T cell, and (3) one or more intracellular signaling domains. The term “activity” includes activities such as the binding specificity / affinity of an antibody or ADC for an antigen, e.g., an anti-hEGFR antibody that binds to an hEGFR antigen and / or the neutralizing potency of an antibody, e.g., an anti-hEGFR antibody whose binding to hEGFR inhibits the biological activity of hEGFR, e.g., inhibition of EGFR phosphorylation in an EGFR-expressing cell line, e.g., the H292 human lung carcinoma cell line, or inhibition of proliferation of EGFR-expressing cell lines, e.g., H292 human lung carcinoma cells, H1703 human lung carcinoma cells, or EBC1 human lung carcinoma cells. The term “non-small cell lung carcinoma (NSCLC) xenograft assay,” as used herein, refers to an in vivo assay used to determine whether an anti-EGFR or ADC antibody can inhibit the Tumor growth (e.g., additional growth) and / or decreased tumor growth resulting from NSCLC cell transplantation into an immunodeficient mouse. An NSCLC xenograft assay involves transplanting NSCLC cells into an immunodeficient mouse such that the tumor grows to a desired size, e.g., between 200 and 250 mm3, after which the antibody or ADC is administered to the mouse to determine whether the antibody or ADC can inhibit and / or decrease tumor growth. In certain embodiments, the activity of the antibody or ADC is determined according to the percentage of tumor growth inhibition (%TGI) relative to a control antibody, e.g., a human IgG antibody (or collection thereof) that does not specifically bind to tumor cells, e.g., is directed against a non-cancer-associated antigen, or is obtained from a non-cancerous source (e.g., normal human serum).In these embodiments, the antibody (or ADC) and the control antibody are administered to the mouse at the same dose, with the same frequency, and via the same route. In one embodiment, the mouse used in the NSCLC xenograft assay is a severe combined immunodeficiency (SCID) mouse and / or an atomic CD-1 mouse. Examples of NSCLC cells that may be used in the NSCLC xenograft assay include, but are not limited to, H292 cells (e.g., NCIH292 [H292] (ATCC® CRL1848™). The term “epitope” refers to a region of an antigen to which an antibody or ADC binds. In certain embodiments, determining epitopes include surface clusters of chemically active molecules, such as amino acids, sugar side chains, phosphoryls, or sulfonyls, and in certain embodiments, they may have specific characteristics. specific in their three-dimensional structure and / or specific charge characteristics. In certain embodiments, an antibody is said to bind specifically to an antigen when it preferentially recognizes its target antigen in a complex mixture of proteins and / or macromolecules. In one particular embodiment, the antibodies of the invention bind to an epitope defined by the amino acid sequence CGADSYEMEEDGVRKC (SEQ ID NO: 45) (which corresponds to amino acid residues 287-302 of the mature form of hEGFR). The term “surface plasmon resonance,” as used herein, refers to an optical phenomenon that enables real-time analysis of biospecific interactions by detecting changes in protein concentrations in a biosensor array, for example, using the BIAcore system (Pharmacia Biosensor AB, Uppsala, Sweden, and Piscataway, NJ). For further descriptions, see Jonsson, U., et al. (1993) Ann. Biol. Clin. 51:19-26; Jonsson, U., et al. (1991) Biotechniques 11:620-627; Johnsson, B., et al. (1995) J. Mol. Recognit. 8:125-131; and Johnsson, B., et al. (1991) Anal. Biochem. 198:268-277. In one embodiment, the surface plasmon resonance is determined according to the methods described in Example 2. The term “kon” or “ka”, as used herein, refers to the rate constant of association of an antibody to the antigen to form the antibody / antigen complex. The term “koff” or “kd”, as used herein, refers to the dissociation rate constant of an antibody from the antibody / antigen complex. The term “Kd”, as used herein, refers to the equilibrium dissociation constant of a particular antibody-antigen interaction (e.g., AbA antibody and EGFR). Kd is calculated as ka / kd. The term “competitive binding,” as used herein, refers to a situation in which a first antibody competes with a second antibody for a binding site on a third molecule, for example, an antigen. In one embodiment, the competitive binding between the two antibodies is determined using FACS assays. The term “competitive binding assay” refers to an assay used to determine whether two or more antibodies bind to the same epitope. In one embodiment, a competitive binding assay is a competitive fluorescence-activated cell sorting (FACS) assay used to determine whether two or more antibodies bind to the same epitope by assessing whether the fluorescent signal of a labeled antibody is reduced by the introduction of an unlabeled antibody, where competition for the same epitope will decrease the fluorescence level. An example of a competitive binding FACS assay is provided in Example 3, which describes a competitive FACS assay using U87MG cells (expressing EGFRvIII). The term “labeled antibody,” as used herein, refers to an antibody, or an antigen-binding portion thereof, with an incorporated label that aids in the identification of the binding protein, e.g., an antibody. Preferably, the label is a detectable mark, e.g., the incorporation of a radiolabeled amino acid or the attachment of biotinylated portions to a polypeptide, where such portions can be detected by labeled avidin (e.g., streptavidin containing a A fluorescent marker or enzymatic activity that can be detected by optical or colorimetric methods). Examples of polypeptide markers include, but are not limited to, the following: radioisotopes or radionuclides (e.g., 3H, 14C, 35S, 90Y, 99Tc, 11In, 125I, 131I, 177Lu, 166Ho, or 153Sm); fluorescent markers (e.g., FITC, rhodamine, lanthanide phosphors); enzymatic markers (e.g., horseradish peroxidase, luciferase, alkaline phosphatase); chemiluminescent markers; biotinyl groups; predetermined polypeptide epitopes that are recognized by a secondary reporter (e.g., leucine zipper sequences, secondary antibody binding sites, metal-binding domains, epitope markers); and magnetic agents, such as gadolinium chelates. The term “antibody-drug conjugate” or “ADC” refers to a binding protein, such as an antibody or antigen-binding fragment thereof, chemically linked to one or more chemical drugs (also referred to herein as agents) that may optionally be therapeutic or cytotoxic agents. In a preferred embodiment, an ADC includes an antibody, a cytotoxic or therapeutic drug, and a linker that enables the binding or conjugation of the drug to the antibody. An ADC typically has either one or eight drug conjugates on either side, including drug-loaded species of 2, 4, 6, or 8.Non-limiting examples of drugs that may be included in ADCs are mitotic inhibitors, antitumor antibiotics, immunomodulatory agents, vectors for gene therapy, alkylating agents, antiangiogenic agents, antimetabolites, boron-containing agents, chemoprotective agents, hormones, antihormonal agents, corticosteroids, photoactive therapeutic agents, oligonucleotides, and other agents. radionuclides, topoisomerase inhibitors, tyrosine kinase inhibitors, and radiosensitizers. The terms “anti-epidermal growth factor antibody-drug conjugate,” “anti-EGFR antibody-drug conjugate,” or “anti-EGFR ADC,” used synonymously herein, refer to an ADC comprising an antibody that binds specifically to EGFR, wherein the antibody is conjugated to one or more chemical agents. In one embodiment, the anti-EGFR ADC is an AbA antibody conjugated to an aurstatin, for example, MMAE or MMAF. The amino acid sequences corresponding to the light and heavy chains of the AbA antibody are provided in SEQ ID NO: 13 and SEQ ID NO: 15, respectively. The term “austatin,” as used herein, refers to a family of antimitotic agents. Austatin derivatives are also included within the definition of the term “austatin.” Examples of auristatins include, but are not limited to, auristatin E (AE), monomethylaustatin E (MMAE), monomethylaustatin F (MMAF), and synthetic dolastatin analogues. In one embodiment, an anti-EGFR antibody described herein is conjugated to an auristatin to form an anti-EGFR ADC. As used herein, the term “AbA-vcMMAE” refers to an ADC comprising the AbA antibody coupled to monomethylaustatin E (MMAE) via a maleimidocaproyl valine citrulline p-aminobenzyloxycarbamil (PABA) connector. The AbA-vcMMAE is described in Figure 11. As used herein, the term “mcMMAF” is used to refer to a maleimidocaproyl-monomethylaustatin F (MMAF) connector / drug combination. The term “drug-to-antibody ratio” or “DAR” refers to the number of drugs, for example, aurstatin, bound to the antibody of the anti-drug complex (ADC). The DAR of an ADC can range from 1 to 8, although higher loads, for example, 10, are also possible, depending on the number of binding sites on an antibody. The term DAR can be used to refer to the number of drugs loaded onto an individual antibody, or, alternatively, it can be used to refer to the average or mean DAR of a group of ADCs. The term “undesired ADC species,” as used herein, refers to any drug-loaded species that must be separated from an ADC species having a different drug load. In one embodiment, the term “undesired ADC species” may refer to species with a drug load of 6 or more, i.e., ADCs with a DAR of 6 or more, including DAR6, DAR7, DAR8, and DAR greater than 8 (i.e., drug-loaded species of 6, 7, 8, or greater than 8). In a separate embodiment, the term “undesired ADC species” may refer to a drug-loaded species of 8 or more, i.e., ADCs with a DAR of 8 or more, including DAR8, and DAR greater than 8 (i.e., drug-loaded species of 8 or greater). The term “ADC mixture,” as used herein, refers to a composition containing a heterogeneous distribution of ADC DARs. In one embodiment, an ADC mixture contains ADCs having a DAR distribution between 1 and 8, for example, 2, 4, 6, and 8 (i.e., species loaded with drugs of 2, 4, 6, and 8). Notably, the products of Degradation may result in the inclusion of drug-loaded species (DARs) of 1, 3, 5, and 7 in the mixture. Additionally, the ADCs in the mixture may also have DARs greater than 8. The ADC mixture results from interchain disulfide reduction followed by conjugation. In one embodiment, the ADC mixture comprises both ADCs with a DAR of 4 or less (i.e., a drug-loaded species of 4 or less) and ADCs with a DAR of 6 or more (i.e., a drug-loaded species of 6 or more). The term “cancer” is intended to describe the physiological condition in mammals typically characterized by unregulated cell growth. Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia or lymphoid malignancies. More specific examples of such cancers include glioblastoma, non-small cell lung cancer, lung cancer, colon cancer, colorectal cancer, head and neck cancer, breast cancer (e.g., triple-negative breast cancer), pancreatic cancer, squamous cell tumors, squamous cell carcinoma (e.g., squamous cell lung cancer or squamous cell head and neck cancer), anal cancer, skin cancer, and vulvar cancer.In one embodiment, the antibodies or ADCs of the invention are administered to a patient who has one or more tumors containing amplifications of the EGFR gene, wherein the tumor expresses the truncated version of EGFR, EGFRvIII. In one embodiment, the antibodies or ADCs of the invention are administered to a patient who has a solid tumor that is likely to overexpress EGFR. In one embodiment, the antibodies or ADCs of the invention are... They are administered to a patient suffering from non-small squamous cell lung cancer (NSCLC). In one embodiment, the antibodies or ADCs of the invention are administered to a patient suffering from solid tumors, including advanced solid tumors. The term “EGFR-expressing tumor,” as used herein, refers to a tumor that expresses the EGFR protein. In one embodiment, EGFR expression in a tumor is determined using immunohistochemical staining of tumor cell membranes, where any immunohistochemical staining above the baseline level in a tumor sample indicates that the tumor is an EGFR-expressing tumor. Methods for detecting EGFR expression in a tumor are known in the art, for example, the EGFR pharmDx™ element set (Dako). Conversely, an “EGFR-negative tumor” is defined as a tumor that has an absence of EGFR membrane staining above the baseline level in a tumor sample as determined by immunohistochemical techniques. The term “EGFRvIII-positive tumor,” as used herein, refers to a tumor that expresses the EGFRvIII protein. In one embodiment, EGFRvIII expression in a tumor is determined using immunohistochemical staining of tumor cell membranes, where any immunohistochemical staining above the baseline level in a tumor sample indicates that the tumor is an EGFRvIII-expressing tumor. Methods for detecting EGFR expression in a tumor are known in the art and include immunohistochemical assays. Conversely, an “EGFRvIII-negative tumor” is defined as a tumor that lacks membrane staining. EGFRvIII above baseline in a tumor sample determined by immunohistochemical techniques. The terms “overexpressed,” “overexpression,” and “overexpressed” are synonymous with referring to a gene that is transcribed or translated at a detectably higher level, usually in a cancer cell, compared to a normal cell. Overexpression therefore refers to the overexpression of protein and mRNA (due to increased transcription, post-transcriptional processing, translation, post-translational processing, altered stability, and altered protein degradation), as well as local overexpression due to altered protein trafficking patterns (increased nuclear localization) and increased functional activity, for example, as in increased enzymatic hydrolysis of substrate. Thus, overexpression refers to protein or RNA levels. Overexpression can also be 50%, 60%, 70%, 80%, 90%, or more compared to a normal cell or a comparison cell.In certain embodiments, the anti-EGFR or ADC antibodies of the invention are used to treat solid tumors that are likely to overexpress EGFR. The term “administer” as used herein refers to the administration of a substance (e.g., an anti-EGFR antibody or ADC) to achieve a therapeutic goal (e.g., the treatment of an EGFR-associated disorder). Routes of administration may be by route of administration. Parenteral, enteric, and topical administration. Parenteral administration is usually by injection and includes, without limitation, intravenous injection and infusion. intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intra-articular, subcapsular, subarachnoid, intraspinal and intrasternal. The term “combination therapy,” as used herein, refers to the administration of two or more therapeutic substances, for example, an anti-EGFR or ADC antibody and an additional therapeutic agent. The additional therapeutic agent may be administered concomitantly with, before, or after the administration of the anti-EGFR or ADC antibody. As used herein, the term “effective amount” or “therapeutically effective amount” refers to the amount of a drug, e.g., an antibody or ADC, that is sufficient to reduce or alleviate the severity and / or duration of a disorder, e.g., cancer, or one or more symptoms thereof, prevent the progression of a disorder, cause the regression of a disorder, prevent the recurrence, development, onset, or progression of one or more symptoms associated with a disorder, detect a disorder, or potentiate or enhance the prophylactic or therapeutic effects of another therapy (e.g., prophylactic or therapeutic agent). The effective amount of an antibody or ADC can, for example, inhibit tumor growth (e.g., inhibit an increase in tumor volume), decrease tumor growth (e.g., decrease tumor volume), reduce the number of cancer cells, and / or alleviate to some extent one or more symptoms associated with cancer.The effective amount can, for example, improve disease-free survival (DFS), improve overall survival (OS), or decrease the likelihood of recurrence. The following subsections describe aspects of the invention in greater detail. II. Anti-EGFR antibodies One aspect of the invention provides anti-EGFR antibodies, or antigen-binding portions thereof, having improved characteristics, for example, increased binding affinity for EGFR, compared to Ab1 and other antibodies known in the art. Another aspect of the invention features antibody-drug conjugates (ADCs) comprising an anti-EGFR antibody described herein and at least one drug, such as, but not limited to, an aurstatin. The antibodies or ADCs of the invention have characteristics that include, by way of example and not limitation, binding to tumor cells expressing EGFRvlll, binding to wild-type EGFR on tumor cells expressing EGFR, recognition of the epitope CGADSYEMEEDGVRKC (SEQ ID NO: 45) on EGFR, binding to EGFR on normal human epithelial keratinocytes, and decreasing or inhibiting the growth of the tumor xenograft in a mouse model. Ab1 (Antibody 1) is a humanized anti-EGFR antibody. The light and heavy chain sequences of Ab1 are described in SEQ ID NO: 13 and SEQ ID NO: 14, respectively (see also U.S. Patent Application Publication No. 20120183471, incorporated herein by reference). The variable region of the Ab1 light chain is described in SEQ ID NO: 5, and comprises a CDR1 amino acid sequence detailed in SEQ ID NO: 6, a CDR2 amino acid sequence detailed in SEQ ID NO: 7, and a CDR3 amino acid sequence detailed in SEQ ID NO: 8. The variable region of the Ab1 heavy chain is described in SEQ ID NO: 1, and comprises a CDR1 amino acid sequence detailed in SEQ ID NO: 2, a CDR2 amino acid sequence detailed in SEQ ID NO: 3, and a CDR3 amino acid sequence detailed in SEQ ID NO: 4. Generally, the Ab1 variant antibodies of the invention retain the epitope specificity of the parental antibody Ab1. Therefore, in one embodiment, the anti-EGFR antibodies of the invention have the ability to bind to an epitope on EGFR defined by SEQ ID NO: 45 and / or have the ability to compete with Ab1 for EGFR binding. In different embodiments, the binding can be studied according to the protocol detailed in Example 3 below. In a preferred embodiment of the invention, the anti-EGFR antibodies compete with Ab1 and have an enhanced binding affinity, for example, a dissociation constant (Kd) between approximately 1 x 10⁻⁶ M and approximately 1 x 10⁻¹⁰ M, determined by surface plasmon resonance, against 1-525 of EGFR (SEQ ID NO: 47). In one embodiment, the invention features anti-EGFR antibodies that are variants of Ab1 and have improved characteristics, such as enhanced binding affinity and the ability to inhibit NSCLC tumor cell proliferation in vivo, as described in the Examples below. Collectively, these novel antibodies are referred to herein as “Ab1 variant antibodies.” Generally, the Ab1 variant antibodies retain the same epitope specificity as Ab1.Therefore, in one embodiment, the anti-EGFR antibodies, or antigen-binding portions thereof, of the invention bind to an epitope in the amino acid sequence detailed in SEQ ID NO: 45 and compete with an anti-EGFR antibody comprising a heavy-chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 1 and a light-chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 5 for binding to EGFRvIII in a competitive binding assay. Unlike Ab1, the anti-EGFR antibodies of the invention have the ability to inhibit or decrease tumor growth in vivo in a human H292 non-small cell lung carcinoma (NSCLC) xenograft assay in an aumic mouse and / or bind to wild-type EGFR on normal human epithelial keratinocytes. In different embodiments, the anti-EGFR antibodies, or antigen-binding fragments thereof, of the invention have the ability to modulate a biological function of EGFR. In other embodiments of the foregoing, the anti-EGFR antibody, or antigen-binding fragment thereof, binds to EGFRvIII, binds to EGFR on EGFR-overexpressing cells, and recognizes the epitope CGADSYEMEEDGVRKC (SEQ ID NO: 45) on EGFR. In a further embodiment, the anti-EGFR antibody, or antigen-binding fragment thereof, binds to EGFRvIII at an epitope that is different from the EGFRvIII binding peptide.In further embodiments of the preceding aspects, the anti-EGFR antibody, or its antigen-binding fragment, does not compete with cetuximab for EGFR binding. The AbA antibody and the Ab1 variants described in the examples below have the aforementioned characteristics. Therefore, the invention includes anti-EGFR antibodies, or antigen-binding portions thereof, that can compete with Ab1 in a competitive binding assay but are more effective in inhibiting or reducing tumor growth. In one embodiment, the anti-EGFR antibodies, or antigen-binding portions thereof, of the invention have the ability to bind to an epitope in the amino acid sequence CGADSYEMEEDGVRKC (SEQ ID NO: 45) and compete with Ab1 (or an anti-EGFR antibody comprising a heavy-chain variable domain comprising the sequence of amino acids detailed in SEQ ID NO: 1 and a light chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 5) by binding to epidermal growth factor receptor variant III (EGFRvIII) (SEQ ID NO: 33) in a competitive binding assay. In one embodiment, the anti-EGFR antibodies, or antigen-binding portions thereof, of the invention bind to EGFR(1-525) (SEQ ID NO: 47) with a dissociation constant (Kd) of approximately 1 x 10⁻⁶ M or less, as determined by surface plasmon resonance. Alternatively, the antibodies, or antigen-binding portions thereof, bind to EGFR(1-525) (SEQ ID NO: 47) with a Kd between approximately 1 x 10⁻⁶ M and approximately 1 x 10⁻¹⁰ M, as determined by surface plasmon resonance. In an additional alternative, antibodies, or antigen-binding portions thereof, bind to EGFR (1-525) (SEQ ID NO: 47) with a Kd between approximately 1 x 10-6 M and approximately 1 x 10-7 M, as determined by surface plasmon resonance.Alternatively, the antibodies, or antigen-binding portions thereof, of the invention bind to EGFR (1-525) (SEQ ID NO: 47) with a Kd between approximately 1 x 10-6 M and approximately 5 x 10-10 M; a Kd between approximately 1 x 10-6 M and. approximately 1 x 10-9 M; a Kd between approximately 1 x 10-6 M and approximately 5 x 10-9 M; a Kd between approximately 1 x 10-6 M and approximately 1 x 10-8 M; a Kd between approximately 1 x 10-6 M and approximately 5 x 10⁻⁸ M; a Kd between approximately 5.9 x 10⁻⁷ M and approximately 1.7 x 10⁻⁹ M; a Kd between approximately 5.9 x 10⁻⁷ M and approximately 2.2 x 10⁻⁷ M, determined by surface plasmon resonance. In certain embodiments, the dissociation constant (Kd) of The antibodies and antigen-binding fragments of the invention, in one embodiment, are less than the dissociation constant for Ab1 but greater than the speed of the anti-EGFR antibody cetuximab. An advantage of the anti-EGFR antibodies, and antigen-binding portions thereof, of the invention is that the antibodies have the ability to bind to tumor cells expressing EGFRvIII. Although EGFRvIII is associated with certain types of cancer, many anti-EGFR antibodies known in the art, for example, cetuximab, are not effective in inhibiting or reducing tumor growth in tumors expressing EGFRvIII. Therefore, in one embodiment, the antibodies, or antigen-binding portions thereof, of the invention bind to EGFRvIII (SEQ ID NO: 33) with a Kd of approximately 8.2 x 10⁻⁹ M or less, as determined by surface plasmon resonance. Alternatively, the antibodies, or antigen-binding portions thereof, of the invention bind to EGFRvIII (SEQ ID NO: 33) with a Kd between approximately 8.2 x 10-9 M and approximately 6.3 x 10-10 M; a Kd between approximately 8.2 x 10-9 M and approximately 2.0 x 10-9 M; a Kd between approximately 2.3 x 10-9 M and approximately 1.5 x 10-10 M, determined by surface plasmon resonance. The antibodies of the invention have the ability, in one embodiment, to inhibit or reduce tumor growth in an in vivo mouse model of xenograft. For example, the antibodies, or antigen-binding portions thereof, of the invention have the ability to inhibit tumor growth by at least approximately 50% in an in vivo small cell lung carcinoma (NSCLC) xenograft assay. human with respect to a human IgG antibody that is not EGFR-specific. In certain embodiments, the antibodies, or antigen-binding portions thereof, of the invention have the ability to inhibit or reduce tumor growth in an in vivo assay of human small cell lung carcinoma (NSCLC) xenograft with respect to a human IgG antibody that is not EGFR-specific by at least approximately 55%, at least approximately 60%, at least approximately 65%, at least approximately 70%, at least approximately 75%, or at least approximately 80%, when administered at the same dose and dosing frequency.In certain embodiments, the antibodies, or antigen-binding portions thereof, of the invention have the ability to inhibit or reduce tumor growth in an in vivo assay of human small cell lung carcinoma (NSCLC) xenograft against a human IgG antibody that is not EGFR-specific by approximately 80% to approximately 90%, or approximately 84% to approximately 90%, or approximately 88% to approximately 90%, when administered at the same dose and dosing frequency. The term “xenograft trial”, as used herein, refers to a human tumor xenograft trial, in which human tumor cells are transplanted, either under the skin or into the type of organ in which the tumor originated, into immunocompromised mice that do not reject human cells. It should be noted that anti-EGFR antibodies, or antigen-binding portions thereof, have combinations of the characteristics The aforementioned embodiments are also considered to be forms of implementation of the invention. For example, the antibodies of the invention can bind to EGFR(1-525) (SEQ ID NO: 47) with a dissociation constant (Kd) of approximately 1 x 10-6 M or less, as determined by surface plasmon resonance, and bind to an epitope with the amino acid sequence CGADSYEMEEDGVRKC (SEQ ID NO: 45) and compete with Ab1 (or an anti-EGFR antibody comprising a heavy chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 1 and a light chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 5) for binding to epidermal growth factor receptor variant III (EGFRvIII) (SEQ ID NO: 33) in a competitive binding assay. In certain embodiments, anti-EGFR antibodies, or antigen-binding portions thereof, bind to an epitope in the amino acid sequence CGADSYEMEEDGVRKC (SEQ ID NO: 45) and compete with Ab1 (or an anti-EGFR antibody comprising a heavy chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 1 and a light chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 5) for binding to epidermal growth factor receptor variant III (EGFRvIII) (SEQ ID NO: 33) in a competitive binding assay; and bind to EGFRvIII (SEQ ID NO: 33) with a Kd of approximately 8.2 x 10-9 M or less, as determined by surface plasmon resonance. In certain embodiments, anti-EGFR antibodies, or antigen-binding portions thereof, bind to an epitope in the sequence of amino acids CGADSYEMEEDGVRKC (SEQ ID NO: 45) and compete with Ab1 (or an anti-EGFR antibody comprising a heavy chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 1 and a light chain variable domain comprising the amino acid sequence detailed in SEQ ID NO: 5) for binding to epidermal growth factor receptor variant III (EGFRvIII) (SEQ ID NO: 33) in a competitive binding assay; and inhibits or reduces tumor growth in an in vivo mouse model of xenograft. More specifically, the antibodies, or antigen-binding portions thereof, of the invention have the ability to inhibit tumor growth by at least approximately 50% in an in vivo assay of human small cell lung carcinoma (NSCLC) xenograft against a human IgG antibody that is not EGFR-specific when administered at the same dose and dosing frequency.Alternatively, the antibodies, or antigen-binding portions thereof, of the invention have the ability to inhibit or reduce tumor growth in an in vivo assay of human small cell lung carcinoma (NSCLC) xenograft against a human IgG antibody that is not EGFR-specific by at least approximately 55%, at least approximately 60%, at least approximately 65%, at least approximately 70%, at least approximately 75%, or at least approximately 80%, when administered at the same dose and dosing frequency. In certain embodiments, the antibodies, or antigen-binding portions thereof, of the invention have the ability to inhibit or reduce tumor growth in an in vivo assay of human small cell lung carcinoma (NSCLC) xenograft against an IgG antibody. human that is not specific for EGFR between approximately 80% and approximately 90%, or between approximately 84% and approximately 90%, or between approximately 88% and approximately 90%, when administered at the same dose and dosing frequency. Antibodies having combinations of any of the aforementioned characteristics are considered aspects of the invention. The ADCs of the invention, described in further detail below, may also have any of the preceding characteristics. In one embodiment, the invention includes an anti-hEGFR antibody, or antigen-binding portion thereof, comprising an LC CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 40, an LC CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 39, and an LC CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 38; and an HC CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 37, an HC CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 36, and an HC CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 35. In one embodiment, the invention includes an anti-hEGFR antibody, or antigen-binding portion thereof, comprising a variable heavy chain region comprising an amino acid sequence selected from the group consisting of 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, and 78; and a variable light chain region comprising a amino acid sequence selected from the group consisting of 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, and 79. In one embodiment, the invention includes an anti-hEGFR antibody, or antigen-binding portion thereof, comprising a set of HC CDRs (CDR1, CDR2, and CDR3) selected from the group consisting of SEQ ID NOs: 10, 11, and 12; SEQ ID NOs: 16, 17, and 18; SEQ ID NOs: 10, 11, and 19; SEQ ID NOs: 20, 11, and 12; SEQ ID NOs: 21, 3, and 22; SEQ ID NOs: 16, 17, and 19; SEQ ID NOs: 2, 3, and 4; SEQ ID NOs: 10, 3, and 12; SEQ ID NOs: 80, 11, and 18; SEQ ID Nos: 80, 3, and 18; SEQ ID Nos: 20, 3, and 12; SEQ ID Nos: 80, 11, and 12; and SEQ SEQ IDs: 81, 11, and 22; and a set of LC light chain CDRs (CDR1, CDR2, and CDR3) selected from the group consisting of SEQ IDs: 6, 7, and 8; SEQ IDs: 23, 24, and 25; SEQ IDs: 26, 27, and 28; SEQ IDs: 29, 30, and 31; SEQ IDs: 6, 7, and 84; SEQ IDs: 82, 83, and 31; and SEQ ID Nos: 82, 27, and 85, wherein the antibody, or antigen-binding portion thereof, does not comprise either the HC CDR set of SEQ ID Nos: 2, 3, and 4, and the LC CDR set of SEQ ID Nos: 6, 7, and 8. Preferably, the anti-EGFR antibodies of the invention exhibit a high capacity to reduce or neutralize EGFR activity, as evaluated by any of the various in vitro and in vivo assays known in the art. For example, the inhibition of EGFR phosphorylation can be measured in an EGFR-expressing cell line, such as the h292 cell line. In certain embodiments, the isolated antibody, or the antigen-binding portion thereof, is bound to human EGFR, wherein the antibody, or the antigen-binding portion thereof, dissociates from human EGFR (EGFR 1-525) with a rate constant Kd of approximately 5.9 x 10⁻⁷ M or less. determined by surface plasmon resonance. Alternatively, the antibody, or an antigen-binding portion thereof, can dissociate from human EGFR (1-525) with a rate constant Kd of approximately 4.2 x 10⁻⁷ M, determined by surface plasmon resonance. Alternatively, the antibody, or an antigen-binding portion thereof, can dissociate from human EGFR (1-525) with a rate constant Kd of approximately 2.5 x 10⁻⁷ M, determined by surface plasmon resonance. In certain embodiments, the anti-EGFR antibodies, or antigen-binding portions thereof, of the invention have a rate constant Kd between 5.9 x 10⁻⁷ M and 5 x 10⁻⁹ M. Alternatively, the antibody, or an antigen-binding portion thereof, can dissociate from human EGFRvIII with a rate constant Kd of approximately 6.1 x 10⁻⁹ M or less, as determined by surface plasmon resonance. Alternatively, the antibody, or an antigen-binding portion thereof, can dissociate from human EGFRvlll with a rate constant Kd of approximately 3.9 x 10⁻⁹ M or less, as determined by surface plasmon resonance. Alternatively, the antibody, or an antigen-binding portion thereof, can dissociate from human EGFRvlll with a rate constant Kd of approximately 2.3 x 10⁻⁹ M or less, as determined by surface plasmon resonance. In one embodiment, the invention features an anti-EGFR antibody, or antigen-binding portion thereof, which is antibody AbA. AbA has an improved binding affinity for EGFR compared to Ab1, and also exhibits unique in vitro and in vivo characteristics relative to Ab1. AbA binds to EGFR in an in vitro keratinocyte binding assay with a much higher affinity. greater than that of Ab1. Additionally, AbA has the ability to inhibit or decrease tumor growth in an H292 cell xenograft assay. Notably, AbA has improved in vitro and in vivo characteristics that are comparable to other Ab1 antibody variants that had higher binding affinity than AbA. Despite having lower binding affinity compared to other Ab1 antibody variants (see, for example, AbP and AbQ vs. AbA in Figure 3), AbA was comparable in inhibiting cell growth in an in vivo assay. The term “AbA” is intended to include an IgG antibody that has at least all six AbA CDRs. The AbA antibody has the same light chain as Ab1, but has a heavy chain that contains six amino acid sequence changes relative to the parental Ab1 antibody (four amino acid changes in the variable region and two changes in the constant region of the heavy chain).The AbA antibody comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 12, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 10, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 8, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 7, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 6. The variable region of the AbA heavy chain is defined by the sequence of amino acids detailed in SEQ ID NO: 9, and a variable region of the chain lightweight comprising the amino acid sequence of SEQ ID NO: 5. The full-length heavy chain of the AbA antibody is detailed in the amino acid sequence described in SEQ ID NO: 15, while the full-length light chain of the AbA antibody is detailed in the amino acid sequence described in SEQ ID NO: 13 (see Figure 2). The following is the nucleic acid sequence of the heavy chain of AbA: gaggtgcaactccaagagagagcgggcggcgtcgtgaagccctctcagactctctctcctgacttgcactgtga gcgggtattccatcagcagagactcgcatggaactggacgcgcgcgcgcggc tgggtacatcagctacaacggtaatacgctatcagccctccctgaagtctcgcattaccattagtcgcgat acctccaagaaccagttcttctgaaactcaacagcgtgacagccgctgacaccgccacctactactgcgtga ccgccagcagggttcccttactggggccagggcactctgtcaccgtctctcgcgcgaccaagggcc atcggtcttccccctggcaccctccc gactacttccccgaaccggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcaccttcccg gctgtcctacagctcgacctacatctgcaacgtgaatcacaagcccagcaaccaaggtggacaagaaagttgagcccaaatctt gccaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagtctctctctcc acgaagaccctgaggtcaagttcaacctggtacgtggacggcgtggaggtgcataatgccaagacaaagcc gcgggaggagcagtacaagcacgtaccgtggtcgcgtcctcaccgtcctgcaccaggactggctga atgcaaggagtacaagtgcaaggtctccaacacccctccatc agccaaagggcagccccgagaaccacaggtgtacaccctgcccccatcccgcgaggagatgaccaaga accaggtcagcctgacctgcctgtcaaggcttctatcccagcgacatcgccgtggagtggggagcaatg ggcagccggagaaactacaagacgcctccgtgctggactccgacggctccttctctctctacagca agctcaccgtggacaagagcaggtggcgcagggaacgtcttctcatgctccgtgatgcatgaggctctgc acaaccactacacgcagaagagccctcctctact (SEQ6) The following is the nucleic acid sequence of the light chain of AbA: Gacatccagatgacccagtccccctccagtatgtctgtgtgtgtgggcgaccgtgtgaccattacctgccactcc tcccaggacatcaatagcaatatcggttggttgcaacagaagccaggcaagtccttcaaagggctgatttacc atggtaccaacctggacgacggttctagtc atcagcagtttgcagcctgaggactttgctacctattgtgtgcagtacgctcagttcccatggactttcggcgg gggcaccaaactggagatcaaacgtacggtggctgcaccatctgtcttcatcttcccgccatctgatgagcagt tgaaatctggaactgcctctgttgtgtgcctgctgaataacttctatcccagagaggccaaagtacagtggaag gtggataacgccctccaatcgggtaactcccaggagagtgtcacagagcaggacagcagacagcacct acagcctcagcagcaccctgacgctgagcaaagcagactacgagaaacacaaagtctacgcctgcgaag tcacccatcagggcctgagctcgcccgtcacaaagagcttcaaggggagagtgt (SEQ ID NO: 87) In one embodiment, the invention presents an antibody EGFR, or the antigen-binding portion thereof, which is the AbB antibody. The AbB antibody comprises a variable heavy chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 19, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 17, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 16, and a variable light chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 8, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 7, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 6. In other embodiments, the invention provides an antibody having a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 64 and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 65. In one embodiment, the invention presents an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbC antibody. The AbC antibody comprises a variable heavy chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 3, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 2, and a variable light chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 84, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 7, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 6.In other embodiments, the invention provides an antibody having a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 66 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 67. In one embodiment, the invention presents an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbD antibody. The AbD antibody comprises a variable heavy-chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 3, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 2, and a variable light-chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 31, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 83, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 82. In other embodiments, the invention provides an antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 68 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 69. In one embodiment, the invention presents an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbE antibody. The AbE antibody comprises a variable heavy chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 3, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 2, and a variable light chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 85, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 27, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 82.In other embodiments, the invention provides an antibody having a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 50 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 51. In one embodiment, the invention features an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbF antibody. The AbF antibody comprises a variable region of the heavy chain that It comprises a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 12, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 3, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 10, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 8, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 7, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 6. In other embodiments, the invention provides an antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 52 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 53. In one embodiment, the invention features an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbG antibody. The AbG antibody comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 18, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 17, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 16, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 25, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 24, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 23. In other embodiments, the invention provides an antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 72 and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 73. In one embodiment, the invention presents an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbH antibody. The AbH antibody comprises a variable heavy chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 18, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 80, and a variable light chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 25, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 24, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 23.In other embodiments, the invention provides an antibody having a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 54 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 55. In one embodiment, the invention presents an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbJ antibody. The AbJ antibody comprises a heavy-chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 18, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 3, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 80, and a light-chain variable region comprising a CDR3 domain comprising the sequence of amino acids of SEQ ID NO: 25, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 24, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 23. In other embodiments, the invention provides an antibody having a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 56 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 57. In one embodiment, the invention presents an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbK antibody. The AbK antibody comprises a variable heavy chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 19, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 10, and a variable light chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 28, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 27, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 26.In other embodiments, the invention provides an antibody having a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 74 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 75. In one embodiment, the invention features an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbL antibody. The AbL antibody comprises a variable region of the heavy chain that It comprises a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 18, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 80, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 28, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 27, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 26. In other embodiments, the invention provides an antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 58 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 59. In one embodiment, the invention features an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbM antibody. The AbM antibody comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 12, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 20, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 28, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 27, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 26. In other embodiments, the invention provides an antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 76 and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 77. In one embodiment, the invention presents an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbN antibody. The AbN antibody comprises a variable heavy chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 12, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 3, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 20, and a variable light chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 28, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 27, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 26.In other embodiments, the invention provides an antibody having a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 60 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 61. In one embodiment, the invention presents an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbO antibody. The AbO antibody comprises a variable heavy-chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 12, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 80, and a variable light-chain region comprising a CDR3 domain comprising the sequence of amino acids of SEQ ID NO: 28, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 27, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 26. In other embodiments, the invention provides an antibody having a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 62 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 63. In one embodiment, the invention presents an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbP antibody. The AbP antibody comprises a variable heavy chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 22, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 3, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 21, and a variable light chain region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 31, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 30, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 29.In other embodiments, the invention provides an antibody having a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 78 and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 79. In one embodiment, the invention features an anti-EGFR antibody, or antigen-binding portion thereof, which is the AbQ antibody. The AbQ antibody comprises a variable region of the heavy chain that It comprises a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 22, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 81, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 31, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 30, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 29. In other embodiments, the invention provides an antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 70 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 71. As described in Table 1 in the examples described below, the Ab1 antibody variant sequences provide consensus amino acid sequences representing CDR domains that result in enhanced Ab1 binding to the EGFR epitope. Therefore, in one embodiment, the invention presents an anti-EGFR antibody, or antigen-binding portion thereof, comprising a light-chain variable region comprising a CDR3 domain comprising the amino acid sequence designated as SEQ ID NO: 40, a CDR2 domain comprising the amino acid sequence designated as SEQ ID NO: 39, and a CDR1 domain comprising the amino acid sequence designated as SEQ ID NO: 38; and a heavy-chain variable region comprising a CDR3 domain comprising the amino acid sequence designated as SEQ ID NO: 37, a CDR2 domain comprising the amino acid sequence designated as SEQ ID NO: 36, and a CDR1 domain comprising the amino acid sequence indicated as SEQ ID NO: 35. In one embodiment, the anti-epidermal growth factor receptor (anti-EGFR) antibody, or antigen-binding portion thereof, comprises a variable region of the heavy chain comprising an amino acid sequence selected from the group consisting of 50, 52, 53, 56, 58, 60, 62, 64, 66, and 68; and a variable region of the light chain comprising an amino acid sequence selected from the group consisting of 51, 53, 55, 57, 59, 61, 63, 65, 67, and 69. In a further embodiment, the anti-EGFR antibody, or antigen-binding portion thereof, of the invention comprises a heavy chain variable region comprising a CDR3 domain comprising an amino acid sequence as indicated in SEQ ID NO: 12, 18, 19, and 22; a CDR2 domain comprising an amino acid sequence as indicated in SEQ ID NO: 11 or 17; and a CDR1 domain comprising an amino acid sequence as indicated in SEQ ID NO: 10, 16, 20, and 21; and a light chain variable region comprising a CDR3 domain comprising an amino acid sequence as indicated in SEQ ID NO: 8, 25, 28, and 31; a CDR2 domain comprising an amino acid sequence as indicated in SEQ ID NO: 7, 24, 27, and 30; and a CDR1 domain comprising an amino acid sequence as indicated in SEQ ID NO: 6, 23, 26 and 29. Phosphorylation and proliferation assays showed that the antibodies described herein inhibited EGFR-mediated phosphorylation and tumor cell growth. For example, as described in Example 6, It was shown that the antibodies against EGFR (as assayed) of the invention inhibited tumor growth in vivo. The preceding CDR sequences of the anti-EGFR antibody established a novel family of EGFR-binding proteins, isolated according to this invention, and comprising polypeptides that include the CDR sequences listed in Tables 1 to 3 below. To generate and select the CDRs that have preferential EGFR binding and neutralization activity compared to hEGFR, standard methods known in the art can be used to generate antibodies, or antigen-binding portions thereof, and to evaluate the EGFR binding and / or neutralization characteristics of those antibodies, or antigen-binding portions thereof, including, but not limited to, those specifically described herein. In certain embodiments, the antibody comprises a heavy chain constant region, such as a constant region of IgG1, IgG2, IgG3, IgG4, IgA, IgE, IgM, or IgD. In certain embodiments, the anti-EGFR antibody, or the antigen-binding portion thereof, comprises an immunoglobulin heavy chain constant domain selected from the group consisting of a human IgG constant domain, a human IgM constant domain, a human IgE constant domain, and a human IgA constant domain. In other embodiments, the antibody, or the antigen-binding portion thereof, has an IgG1 heavy chain constant region, an IgG2 heavy chain constant region, an IgG3 heavy chain constant region, or an IgG4 heavy chain constant region. Preferably, the heavy chain constant region is a The antibody may comprise a heavy chain constant region of IgG1 or a heavy chain constant region of IgG4. Furthermore, the antibody may comprise a light chain constant region, a kappa light chain constant region, or a lambda light chain constant region. Preferably, the antibody comprises a kappa light chain constant region. Alternatively, the antibody portion may be, for example, a Fab fragment or a single-chain Fv fragment. In certain embodiments, the binding portion of the anti-EGFR antibody is a Fab, a Fab', an F(ab')2, an Fv, an Fv with disulfide linkage, an scFv, a single-domain antibody, or a divalent antibody. In certain embodiments, the anti-EGFR antibody, or antigen-binding portion thereof, is a multispecific antibody, for example a bispecific antibody. In certain embodiments, the anti-EGFR antibody, or antigen-binding portion thereof, comprises a heavy chain constant region comprising the amino acid sequence detailed in SEQ ID NO: 41 and / or a light chain constant region comprising the amino acid sequence detailed in SEQ ID NO: 43. Replacements of amino acid residues in the Fc portion have been described to alter the effector function of the antibody (Winter et al., U.S. Patents Nos. 5,648,260 and 5,624,821, which are incorporated herein by reference). The Fc portion of an antibody mediates several important effector functions, including cytokine induction, ADCC, phagocytosis, complement-mediated cytotoxicity (CDC), and the clearance rate / half-life of antibodies and antigen-antibody complexes. In some cases, these effector functions are desirable for therapeutic antibodies, but in others, they may be unnecessary or even detrimental, depending on the therapeutic objectives. Certain human IgG isotypes, particularly IgG1 and IgG3, mediate ADCC and CDC through binding to FcyRs and complement C1q, respectively. Neonatal Fc receptors (FcRn) are critical components in determining the circulating half-life of antibodies. In yet another embodiment, at least one amino acid residue is replaced in the antibody's constant region, for example, the Fc region, thereby altering these effector functions. One embodiment of the invention includes a recombinant chimeric antigen receptor (CAR) comprising the antibody-binding regions described herein, e.g., the heavy and / or light chain CDRs of AbA. A recombinant CAR, as described herein, can be used to redirect T cell specificity to an antigen in a human leukocyte antigen (HLA)-independent manner. Therefore, the CARs of the invention can be used in immunotherapy to help design the human subject's own immune cells to recognize and attack the subject's tumor (see, for example, U.S. Patents Nos. 6,410,319; 8,389,282; 8,822,647; 8,906,682; 8,911,993; 8,916,381; 8,975,071; and U.S. Patent Application Publication No. US20140322275, each of which is incorporated herein by reference with respect to CAR technology).This type of immunotherapy is called adoptive cell transfer (ACT), and it can be used to treat cancer in a subject who needs it. An anti-EGFR CAR of the invention preferably contains an EGFR-specific extracellular antigen-binding domain (e.g., EGFRvIII), a transmembrane domain used to anchor the CAR to a T cell, and one or more intracellular signaling domains. In one embodiment of the invention, the CAR includes a transmembrane domain comprising a transmembrane protein domain selected from the group consisting of the alpha, beta, or zeta chain of the T cell receptor CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, and CD154. In one embodiment of the invention, the CAR comprises a costimulatory domain, for example, a costimulatory domain comprising a functional signaling domain of a protein selected from the group consisting of OX40, CD2, CD27, CD28, CD5, ICAM-1, LFA-1 (CD11a / CD18), ICOS (CD278), and 4-1BB (CD137). In certain forms of In carrying out the invention, the CAR comprises an scFv comprising the CDR or variable regions described herein, e.g., CDR or variable regions of the AbA antibody, a transmembrane domain, a costimulatory domain (e.g., a functional signaling domain of CD28 or 4-1BB), and a signaling domain comprising a functional signaling domain of CD3 (e.g., CD3-zeta). In certain embodiments, the invention includes a T cell comprising a CAR (also preferred as a CAR T cell) comprising antigen-binding regions, for example CDRs, of the antibodies described herein or an scFv described herein. In certain embodiments of the invention, the CAR comprises a variable region of the light chain comprising a CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO:40, a CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 39, and a CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 38; and a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 37, a CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 36, and a CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 35. In certain embodiments of the invention, the CAR comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 12, a CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 10; and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence detailed in SEQ ID NO: 8, a CDR2 domain comprising the amino acid sequence detailed in SEQ ID NO: 7, and a CDR1 domain comprising the amino acid sequence detailed in SEQ ID NO: 6. One embodiment of the invention includes a labeled anti-EGFR antibody, or an antibody portion thereof, wherein the antibody is derivatized or linked to one or more functional molecules (e.g., another peptide or protein). For example, a labeled antibody or antibody portion of the invention may be derived by functional linkage (by chemical coupling, genetic fusion, non-covalent association, or otherwise) to one or more other molecular entities, such as another antibody. (for example, a bispecific antibody or a divalent antibody), a detectable agent, a pharmaceutical agent, a protein or peptide that can mediate the association of the antibody or portion of the antibody with another molecule (such as a streptavidin core region or a polyhistidine tag), and / or a cytotoxic or therapeutic agent selected from the group consisting of a mitotic inhibitor, an antitumor antibiotic, an immunomodulatory agent, a gene therapy vector, an alkylating agent, an antiangiogenic agent, an antimetabolite, a boron-containing agent, a chemoprotective agent, a hormone, an antihormonal agent, a corticosteroid, a photoactive therapeutic agent, an oligonucleotide, a radionuclide agent, a topoisomerase inhibitor, a tyrosine kinase inhibitor, a radiosensitizer, and a combination thereof. Useful detectable agents with which an antibody or antibody portion thereof can be derivatized include fluorescent compounds. Examples of detectable fluorescent agents include fluorescein, fluorescein isothiocyanate, rhodamine, 5-dimethylamine-1-napphalensulfonyl chloride, phycoerythrin, and the like. An antibody can also be derivatized with detectable enzymes, such as alkaline phosphatase, horseradish peroxidase, glucose oxidase, and the like. When the antibody is derivatized with a detectable enzyme, it is detected by adding additional reagents that are used by the enzyme to generate a detectable reaction product. For example, when horseradish peroxidase is present as a detectable agent, the addition of hydrogen peroxide and diaminobenzidine generates a colored reaction product, which It can be detected. An antibody can also be derivatized with biotin and detected through an indirect measure of avidin or streptavidin binding. In one embodiment, the antibody of the invention is conjugated with an imaging agent. Examples of imaging agents that may be used in the compositions and methods described herein include, but are not limited to, a radiolabel (e.g., indium), an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and biotin. In one embodiment, the antibodies or ADCs are linked to a radiolabel, such as, but not limited to, indium (111In). 111Indium can be used to label the antibodies and ADCs described herein for use in identifying EGFR-positive tumors. In another embodiment, the anti-EGFR antibodies (or ADCs) described herein are labeled with 111I via a bifunctional chelating agent that is a bifunctional chelating agent of cyclohexyl diethylenetriaminepentaacetic acid (DTPA) (see U.S. Patents 5,124,471; 5,434,287; and 5,286,850, each of which is incorporated herein by reference). Another embodiment of the invention provides a glycosylated binding protein wherein the anti-EGFR antibody or antigen-binding portion thereof comprises one or more carbohydrate residues. Native in vivo protein production may include further processing, known as post-translational modification. In particular, sugar (glycosyl) residues may be added enzymatically, a process known as glycosylation. The resulting proteins, containing side chains of Oligosaccharides covalently linked are known as glycosylated proteins or glycoproteins. Antibodies are glycoproteins with one or more carbohydrate residues in the Fc domain, as well as in the variable domain. Carbohydrate residues in the Fc domain have a major effect on the effector function of the Fc domain, with a minor effect on antigen binding or antibody half-life (R. Jefferis, Biotechnol. Prog. 21 (2005), pp. 11-16). Conversely, glycosylation of the variable domain can affect the antigen-binding activity of the antibody. Glycosylation in the variable domain can have a negative effect on antibody binding affinity, probably due to steric hindrance (Co, MS, et al., Mol. Immunol. (1993) 30:1361-1367), or it can result in increased affinity for the antigen (Wallick, SC, et al., Exp. Med. (1988) 168:1099-1109; Wright, A., et al., EMBO J.(1991) 10:2717-2723). One aspect of the present invention relates to the generation of glycosylation site mutants in which the glycosylation site bound to O or N of the binding protein has been mutated. A person skilled in the art can generate such mutants using well-known conventional technologies. Glycosylation site mutants that retain biological activity but have increased or decreased binding activity are another object of the invention. In yet another embodiment, the glycosylation of the anti-EGFR antibody or antigen-binding portion of the invention is modified. For example, it is possible to generate a non-glycosylated antibody (i.e., the antibody lacks glycosylation). The glycosylation can be altered, for example, to increase the antibody's affinity for the antigen. Such modifications of the Carbohydrate modifications can be made, for example, by altering one or more glycosylation sites in the antibody sequence. For instance, one or more amino acid substitutions can be made that result in the deletion of one or more glycosylation sites in the variable region, thereby eliminating glycosylation at that site. Such non-glycosylation can increase the antibody's affinity for the antigen. This approach is described in greater detail in PCT Publication WO2003016466A2 and U.S. Patent Nos. 5714350 and 6350861, each incorporated herein by reference. Additionally or alternatively, a modified anti-EGFR antibody of the invention may be prepared having an altered glycosylation pattern, such as a hypofucosylated antibody having reduced amounts of fucosyl residues or an antibody having increased GlcNAc bifurcated structures. Such altered glycosylation patterns have been shown to increase the ability of antibodies to produce ADCC. Such carbohydrate modifications can be effected, for example, by expressing the antibody in a host cell with the altered glycosylation machinery. Cells with the altered glycosylation machinery, which can be used as host cells to express the recombinant antibodies of the invention and thereby produce an antibody with altered glycosylation, have been described in the art. See, for example, Shields, RL et al. (2002) J. Biol. Chem. 277:26733-26740; Umana et al. (1999) Nat. Biotech.17:176-1, as well as European Patent No: EP 1,176,195; PCT Publications WO 03 / 035835; WO 99 / 54342 80, which are incorporated herein by reference in their entirety. The glycosylation of proteins depends on the amino acid sequence of the protein of interest, as well as on the host cell in which the protein is expressed. Different organisms may produce different glycosylation enzymes (e.g., glycosyltransferases and glycosidases) and may have different substrates (nucleotide sugars) available. Due to these factors, the glycosylation pattern and the composition of glycosidic residues may differ depending on the host system in which the particular protein is expressed. Useful glycosidic residues in the invention may include, but are not limited to, glucose, galactose, mannose, fucose, N-acetylglucosamine, and salicylic acid. Preferably, the glycosylated binding protein comprises glycosidic residues that allow for obtaining a human glycosylation pattern. Different glycosylation of proteins can result in different protein characteristics. For example, the efficacy of a therapeutic protein produced by a host microorganism, such as yeast, and glycosylated using the yeast's endogenous pathway, may be reduced compared to that of the same protein expressed in a mammalian cell, such as an CHO cell line. Such glycoproteins may also be immunogenic in humans and exhibit a reduced in vivo half-life after administration. Specific receptors in humans and other animals can recognize specific glycosidic residues and promote rapid elimination of the protein from the bloodstream. Other adverse effects may include changes in protein folding, solubility, susceptibility to proteases, circulation, transport, compartmentalization, secretion, and recognition by other proteins. factors, its antigenicity, or its allergenicity. Consequently, a practitioner may prefer a therapeutic protein with a specific composition and glycosylation pattern, for example, a glycosylation composition and pattern identical, or at least similar, to those produced in human cells or cells with species specificity from the intended animal subject. The expression of glycosylated proteins different from those of a host cell can be achieved by genetically modifying the host cell to express heterologous glycosylation enzymes. Using recombinant techniques, an assistant can generate antibodies or antigen-binding portions thereof that exhibit human protein glycosylation. For example, yeast strains have been modified to express non-naturally occurring glycosylation enzymes, such as the glycosylated proteins (glycoproteins) produced in these yeast strains that exhibit protein glycosylation identical to that of animal cells, especially human cells (U.S. Patents 20040018590 and 20020137134 and PCT Publication WO2005100584 A2). Antibodies can be produced by any number of techniques. For example, expression from host cells, where the expression vector(s) encoding the heavy and light chains are transfected into a host cell using standard techniques. The various forms of the term “transfection” encompass a wide variety of commonly used procedures for introducing exogenous DNA into a prokaryotic or eukaryotic host cell, for example, electroporation, calcium phosphate precipitation, DEAE-dextran transfection, and the like. Although it is possible to express antibodies in prokaryotic or eukaryotic host cells, It prefers the expression of antibodies in eukaryotic cells, and more preferentially in mammalian host cells, because such eukaryotic cells (and in particular mammalian cells) are more likely than prokaryotic cells to assemble and secrete a properly folded and immunologically active antibody. The preferred mammalian host cells for expressing the recombinant antibodies of the invention include CHO cells (including the CHO dhfr cells described in Urlaub and Chasin, (1980) Proc. Natl. Acad. Sci. USA 77:4216-4220), used in combination with a DHFR selection marker, as described, for example, in RJ Kaufman and PA Sharp (1982) Mol. Biol. 159:601-621), NS0 myeloma cells, COS cells, and SP2 cells. When recombinant expression vectors containing antibody-encoding genes are introduced into mammalian host cells, antibodies are produced by culturing the host cells until the antibody is expressed in those host cells, or preferably, the antibody is secreted into the culture medium in which the host cells are grown. The antibodies can then be isolated from the culture medium using conventional protein purification methods. Similarly, it is possible to use host cells to produce intact antibody portions, such as Fab fragments or scFv molecules. It is understood that variations of the foregoing procedure are within the scope of embodiments. For example, it may be desirable to transfect a host cell with DNA encoding functional fragments of the light and / or heavy chain of an antibody of this invention. Recombinant DNA technology may also be used to remove a portion or The entirety of the DNA encoding the light and / or heavy chain that is not required for binding to the antigens of interest. The molecules expressed from these truncated DNA molecules are also included within the antibodies of the invention. Furthermore, it is possible to produce bifunctional antibodies, where one heavy chain and one light chain are an antibody of the invention, and the other heavy chain and one light chain have specificity for an antigen different from the antigen of interest, by crossing one antibody of the invention with a second antibody, according to conventional chemical crossing methods. In a preferred system for the recombinant expression of an antibody, or an antigen-binding portion thereof, a recombinant expression vector encoding the antibody heavy and light chains is introduced into CHO dhfr- cells via calcium phosphate-mediated transfection. Within the recombinant expression vector, the antibody heavy and light chain genes are operatively linked to regulatory elements, consisting of the CMV enhancer and the AdMLP promoter, to achieve high levels of gene transcription. The recombinant expression vector also contains a DHFR gene, enabling the selection of vector-transfected CHO dhfr- cells using methotrexate selection / amplification. The selected transformed host cells are cultured to express the antibody heavy and light chains, and the intact antibody is isolated from the culture medium.Conventional molecular biology techniques are used to prepare the recombinant expression vector, transfect the host cells, select the transformants, and culture these host cells. and obtaining the antibody from the culture medium. The invention also provides a method for synthesizing a recombinant antibody of the invention by culturing a host cell in a suitable culture medium until a recombinant antibody is synthesized. The recombinant antibodies of the invention can be produced using nucleic acid molecules corresponding to the amino acid sequences described herein. In one embodiment, the nucleic acid molecules detailed in SEQ ID Nos. 86 and / or 87 are used in the production of a recombinant antibody. Furthermore, the method may comprise isolating such a recombinant antibody from the culture medium. III. Anti-EGFR antibody-drug conjugates (ADCs) The anti-EGFR antibodies described herein can be conjugated with a pharmacological group to form an anti-EGFR antibody-drug conjugate (ADC). Antibody-drug conjugates (ADCs) can enhance the therapeutic efficacy of antibodies in the treatment of diseases, such as cancer, due to the ability of the ADC to selectively deliver one or more pharmacological groups to target tissues, such as a tumor-associated antigen, for example, tumors expressing EGFR. Therefore, in certain embodiments, the invention provides anti-EGFR ADCs for therapeutic use, for example, in the treatment of cancer. The anti-EGFR ADCs of the invention comprise an anti-EGFR antibody, i.e., an antibody that binds specifically to EGFR, linked to one or more drug groups. The specificity of the ADC is defined by the specificity of the antibody, i.e., anti-EGFR. In one embodiment, an anti-EGFR antibody is linked to one or more cytotoxic drugs that are They are administered internally to a transformed cancer cell that expresses EGFR. Examples of drugs that may be used in the anti-EGFR ADC of the invention are provided later, as are connectors that may be used to conjugate the antibody and one or more drugs. The terms “drug,” “agent,” and “drug group” are used herein synonymously. The terms “bound” and “conjugated” are also used herein synonymously and indicate that the antibody and group are covalently bound. In some implementations, the ADC has the following formula (formula I): Ab-(LD)n (YO) where Ab is the antibody, for example, anti-EGFR antibody AbA, and (LD) is a drug-linking group. The drug-linking group is composed of L-, which is a linker, and -D, which is a drug group that has, for example, cytostatic, cytotoxic, or other therapeutic activity against a target cell, for example, a cell that expresses EGFR; yn is an integer between 1 and 20. In some embodiments, n ranges from 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or is 1. The DAR of an ADC is equivalent to the “n” referred to in Formula I. In one embodiment, the ADC has the formula Ab-(LD)n, where Ab is an anti-EGFR antibody, e.g., AbA, L is a connector, e.g., valine citrulline (vc), D is a drug, e.g., an aurstatin such as MMAF or MMAE, and yn is between 2 and 4 (equivalent to a DAR between 2 and 4). Details regarding the Drugs (D in Formula I) and connectors (L in Formula I) that can be used in the ADCs of the invention, as well as alternative ADC structures, are described below. A. ADC anti-EGFR: Example drugs for conjugation Anti-EGFR antibodies can be used in ADCs to target one or more drugs to a cell of interest, for example, a cancer cell that expresses EGFR. The anti-EGFR ADCs of the invention provide targeted therapy that can, for example, reduce the side effects frequently observed in anti-cancer therapies, since the one or more drugs are delivered to a specific cell. Austatins The anti-EGFR antibodies of the invention, for example, the AbA antibody, can be conjugated with at least one auristatin. Austatins represent a group of dolastatin analogues that have generally been shown to possess anticancer activity by interfering with microtubule dynamics and GTP hydrolysis, thereby inhibiting cell division. For example, auristatin E (U.S. Patent No. 5,635,483) is a synthetic analogue of the marine natural product dolastatin 10, a compound that inhibits tubulin polymerization by binding to the same site on tubulin as the anticancer drug vincristine (GR Pettit, Prog. Chem. Org. Nat. Prod, 70: 1-79 (1997)). Dolastatin 10, auristatin PE, and auristatin E are linear peptides that have four amino acids, three of which are unique to the dolastatin class of compounds.Exemplary embodiments of the auristatin subclass of mitotic inhibitors include, but not limited to, monomethylaustatin D (MMAD or derivative of). auristatin D), monomethylaustatin E (MMAE or auristatin E derivative), monomethylaustatin F (MMAF or auristatin F derivative), auristatin F phenylenediamine (AFP), auristatin EB (AEB), auristatin EFP (AEFP), and 5-benzoylvaleric acid-AE ester (AEVB). The synthesis and structure of the auristatin derivatives are described in U.S. Patent Application Publications Nos. 2003-0083263, 2005-0238649 and 2005-0009751; International Patent Publication No. WO 04 / 010957, International Patent Publication No. WO 02 / 088172, and U.S. Patent Nos. 6,323,315; 6,239,104; 6,034,065; 5,780,588; 5,665,860; 5,663,149; 5,635,483; 5,599,902; 5,554,725; 5,530,097; 5,521,284; 5,504,191; 5,410,024; 5,138,036; 5,076,973; 4,986,988; 4,978,744; 4,879,278; 4,816,444; and 4,486,414, each of which is incorporated herein by reference. In one embodiment, the anti-EGFR antibodies of the invention, for example, AbA, are conjugated with at least one MMAE Monomethylaustatin E (MMAE, vedotin) inhibits cell division by blocking tubulin polymerization. Due to its Due to its high toxicity, it also cannot be used as a single drug. In current cancer therapy developments, it is linked to a monoclonal antibody (mAb) that recognizes the expression of a specific marker on cancer cells and directs MMAE to the cancer cells. In one embodiment, the linker that joins MMAE to the anti-EGFR antibody is stable in the extracellular fluid (i.e., the medium or environment external to the cells) but is cleaved by cathepsin once the ADC has bound to the antigen. specific cancer cell and has entered the cancer cell, thereby releasing the toxic MMAE and activating the potent antimitotic mechanism. In one embodiment, an anti-EGFR antibody described herein, for example, AbA, is conjugated to at least one MMAF (monomethylaustatin F). Monomethylaustatin F (MMAF) inhibits cell division by blocking tubulin polymerization. It has a charged phenylalanine residue at the C-terminus that attenuates its cytotoxic activity compared to its uncharged counterpart, MMAE. Due to its supertoxicity, it cannot be used as a single drug but can be bound to a monoclonal antibody (mAb) that directs it to cancer cells. In one embodiment, the linker that joins the anti-EGFR antibody is stable in the extracellular fluid but is cleaved by cathepsin once the conjugate has entered the cell. to a tumor cell, thereby activating the anti-mitotic mechanism. The structures of MMAF and MMAE are provided below. Monomethylaustatin F (MMAF) An example of AbA-vcMMAE is also provided in Figure 11. Notably, Figure 11 describes a situation in which the antibody (e.g., AbA) is coupled to a single drug and therefore has a DAR of 1. In certain embodiments, the ADC will have a DAR between 2 and 8, or, alternatively, between 2 and 4. Other drugs for conjugation Examples of drugs that can be used in ADCs, i.e., drugs that can be conjugated with the anti-EGFR antibodies of the invention, are provided later, and include mitotic inhibitors, antitumor antibiotics, immunomodulatory agents, vectors for gene therapy, alkylating agents, antiangiogenic agents, antimetabolites, boron-containing agents, chemoprotective agents, hormonal agents, glucocorticoids, photoactive therapeutic agents, oligonucleotides, radioactive isotopes, radiosensitizers, topoisomerase inhibitors, tyrosine kinase inhibitors, and combinations thereof. 1. mitotic inhibitors In one aspect, anti-EGFR antibodies can be conjugated with one or more mitotic inhibitors to form an anti-drug conjugate (ADC) for cancer treatment. The term “mitotic inhibitor,” as used herein, refers to a cytotoxic and / or therapeutic agent that blocks mitosis, or cell division, a biological process particularly important for cancer cells. A mitotic inhibitor alters microtubules such that cell division is prevented, frequently by affecting microtubule polymerization or depolymerization. Therefore, in one embodiment, an anti-EGFR antibody of the invention is conjugated with one or more mitotic inhibitors that alter microtubule formation by inhibiting tubulin polymerization. In one embodiment, the mitotic inhibitor used in the ADCs of the invention is Ixempra (ixabepilone).Examples of mitotic inhibitors that can be used in the anti-EGFR ADCs of the invention are provided below. Austatins are included in the class of mitotic inhibitors described above. a. Dolastatins The anti-EGFR antibodies of the invention can be conjugated with at least one dolastatin to form an ADC. Dolastatins are short peptide compounds isolated from the Indian Ocean sea hare Dolabella auricularia (see Pettit et al., J. Am. Chem. Soc., 1976, 98, 4677). Examples of dolastatins include dolastatin 10 and dolastatin 15. Dolastatin 15, a seven-unit depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the antitubulin agent dolastatin 10, a five-subunit peptide obtained from the same organism. Therefore, in one embodiment, the anti-EGFR ADC of the invention comprises an anti-EGFR antibody, as described herein, and at least one dolastatin. The auristatins, described above, are synthetic derivatives of dolastatin 10. b. Maitansinoides The anti-EGFR antibodies of the invention can be conjugated with at least one mantisinoid to form an ADC. Maitansinoids are potent antitumor agents that were originally isolated from members of the higher plant families Celastraceae, Rhamnaceae, and Euphorbiaceae, as well as from some moss species (Kupchan et al., J. Am. Chem. Soc. 94:1354-1356

[1972] ; Wani et al., J. Chem. Soc. Chem. Commun. 390:

[1973] ; Powell et al., J. Nat. Prod. 46:660-666

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[1988] ; and Suwanborirux et al., Experientia 46:117-120

[1990] ). Evidence suggests that maytansinoids inhibit mitosis by inhibiting the polymerization of the microtubule protein tubulin, thereby preventing the formation of microtubules (see, for example, U.S. Patent No. 6,441,163 and Remillard et al., Science, 189, 1002-1005 (1975)).Maitansinoides have been shown to inhibit tumor cell growth in vitro using cell culture models, and in vivo using laboratory animal systems. Additionally, the cytotoxicity of maitansinoides is 1,000. times greater than conventional chemotherapeutic agents, such as, for example, methotrexate, daunorubicin, and vincristine (see, for example, U.S. Patent No. 5,208,020). Maitansinoids include maitansine, maitansinol, C-3 esters of maitansinol, and other maitansinol analogues and derivatives (see, for example, U.S. Patents Nos. 5,208,020 and 6,441,163, each of which is incorporated herein by reference). C-3 esters of maitansinol may be of natural origin or synthetically derived. Additionally, both naturally occurring and synthetic C-3 esters of maitansinol may be classified as a C-3 ester with simple carboxylic acids, or a C-3 ester with N-methyl-L-alanine derivatives, the latter being more cytotoxic than the former. Synthetic analogues of maitansinoid are described in, for example, Kupchan et al., J. Med. Chem., 21, 31-37 (1978). The maitansinoids suitable for use in the ADCs of the invention can be isolated from natural sources, produced synthetically, or produced semi-synthetically. Additionally, the maitansinoid can be modified in any way, provided that sufficient cytotoxicity is preserved in the final conjugated molecule. In this respect, maitansinoids lack suitable functional groups to which antibodies can bind. A linker group is desirablely used to join the maitansinoid to the antibody to form the conjugate and is described in more detail in Section IIIB. The structure of an exemplary maitansinoid, mertasin (DM1), is provided later. Mertansine (DM1) Representative examples of maitansinoids include, but are not limited to, DM1 (N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maitansine; also referred to as mertansine, maitansinoid drug 1; ImmunoGen, Inc.; see also Chari et al. (1992) Cancer Res 52:127), DM2, DM3 (N2'-deacetyl-N2'-(4-mercapto-1-oxopentyl)-maitansine), DM4 (4-methyl-4-mercapto-1-oxopentyl)-maitansine), and maitansinol (a synthetic analogue of a maitansinoid). Examples of maitansinoids are described in U.S. Patent No. 8,142,784, which is incorporated herein by reference. Ansamitocins are a group of methasinoid antibiotics that have been isolated from various bacterial sources. These compounds have potent antitumor activity. Representative examples include, but are not limited to, ansamitocin P1, ansamitocin P2, ansamitocin P3, and ansamitocin P4. In one embodiment of the invention, an anti-EGFR antibody is conjugated to at least one DM1. In one embodiment, an anti- EGFR is conjugated to at least one DM2. In one embodiment, an anti-EGFR antibody is conjugated to at least one DM3. In another embodiment, an anti-EGFR antibody is conjugated to at least one DM4. d. Plant alkaloids The anti-EGFR antibodies of the invention can be conjugated with at least one plant alkaloid, for example, a taxane or vinca alkaloid. Plant alkaloids are chemotherapy treatments derived from certain types of plants. Vinca alkaloids are made from the sea snail plant (Catharanthus rosea), while taxanes are made from the bark of the Pacific yew tree (Taxus). Vinca alkaloids and taxanes are also known as antimicrotubule agents and are described in more detail below. Taxanes The anti-EGFR antibodies described herein can be conjugated to at least one taxane. The term “taxane” as used herein refers to the class of antineoplastic agents that have a mechanism of action on microtubules and that have a structure including the taxane ring structure and a stereospecific side chain required for cytostatic activity. Within the term “taxane” are a variety of known derivatives, including both hydrophilic and hydrophobic derivatives. Taxane derivatives include, but are not limited to, galactose and mannose derivatives described in International Patent Application No. WO 99 / 18113; piperazine and other derivatives described in WO 99 / 14209; taxane derivatives described in WO 99 / 09021, WO 98 / 22451, and U.S. Patent No. 5,869,680; 6-thio derivatives described in WO 98 / 28288; sulfenamide derivatives described in U.S. Patent No. 5,821,263; and taxol derivatives described in U.S. Patent No. 5,415,869, each of which are incorporated herein by reference. Taxane compounds have been previously described in U.S. Patents Nos. 5,641,803, 5,665,671, 5,380,751, 5,728,687, 5,415,869, 5,407,683, 5,399,363, 5,424,073, 5,157,049, 5,773,464, 5,821,263, 5,840,929, 4,814,470, 5,438,072, 5,403,858, 4,960,790, 5,433,364, 4,942,184, 5,362,831, 5,705,503, and 5,278,324, all of which are expressly incorporated by reference. Additional examples of taxanes include, but are not limited to, docetaxel (Taxotere; Sanofi Aventis), paclitaxel (Abraxane or Taxol; Abraxis Oncology), and nanoparticulate paclitaxel (ABI-007 / Abraxene; Abraxis Bioscience). In one embodiment, the anti-EGFR antibody of the invention is conjugated to at least one docetaxel. In another embodiment, the anti-EGFR antibody of the invention is conjugated to at least one paclitaxel. Vinca alkaloids In one embodiment, the anti-EGFR antibody is conjugated to at least one vinca alkaloid. Vinca alkaloids are a class of cell cycle-specific drugs that work by inhibiting the ability of cancer cells to divide by acting on tubulin and preventing microtubule formation. Examples of vinca alkaloids that may be used in the ADCs of the invention include, but are not limited to, vindesine sulfate, vincristine, vinblastine, and vinorelbine. 2. Antitumor antibiotics The anti-EGFR antibodies of the invention can be conjugated with one or more antitumor antibiotics for the treatment of cancer. As used herein, the term “antitumor antibiotic” refers to an antineoplastic drug that blocks cell growth by interfering with DNA and is produced by a microorganism. Antitumor antibiotics frequently break DNA strands or slow down or stop DNA synthesis. Examples of antitumor antibiotics that may be included in the anti-EGFR ADCs of the invention include, but are not limited to, actinomycins (e.g., pyrrolo[2,1-c][1,4]benzodiazepines), anthracyclines, calicheamycins, and duocarmycins, which are described in more detail below. a. Actinomycins The anti-EGFR antibodies of the invention can be conjugated to at least one actinomycin. Actinomycins are a subclass of antitumor antibiotics isolated from bacteria of the genus Streptomyces. Representative examples of actinomycins include, but are not limited to, actinomycin D (Cosmegen [also known as actinomycin, dactinomycin, actinomycin IV, actinomycin C1], Lundbeck, Inc.), anthramycin, chycamycin A, DC-81, mazethramycin, neothramycin A, neothramycin B, porothramycin, protracarcin B, SG2285, sibanomycin, sibiromycin, and tomamycin. In one embodiment, the anti-EGFR antibody of the invention is conjugated to at least one pyrrolobenzodiazepine (PBD). Examples of PBDs include, but are not limited to, anthramycin, chycamycin A, DC-81, mazethramycin, neothramycin A, neothramycin B, porothramycin, protracarcin B, SG2000 (SJG-136), SG2202 (ZC-207), SG2285 (ZC-423), sibanomycin, sibiromycin and I amoxicillin. Therefore, in one embodiment, anti-EGFR antibodies of the invention are combined with at least one actinomycin, for example, actinomycin D, or at least one PBD, for example, a pyrrolobenzodiazepine dimer (PBD). The structures of PBDs can be found, for example, in U.S. Patent Applications Nos. 2013 / 0028917 and 2013 / 0028919, and in WO 2011 / 130598 A1, each of which is incorporated herein in full by reference. The generic structure of a PBD is provided below. PBDs differ in the number, type, and position of substituents on the aromatic rings A and pyrrole rings C, and in the degree of saturation of ring C. In ring B, there is generally an imine (N=C), a carbinolamine (NH-CH(OH)), or a carbinolamine methyl ether (NH-CH(OMe)) at the N10-C11 position, which is the electrophilic center responsible for alkylating DNA. All known natural products have a chiral (S) configuration at the C11a position, giving them a right-handed rotation when viewed from ring C to ring A. The examples of PBDs provided herein can be conjugated with the anti-EGFR antibodies of the invention. Other examples of PBDs that can be conjugated with the anti-EGFR antibodies of the invention can be found, for example, in U.S. Patent Application Publications Nos. 2013 / 0028917 A1 and 2013 / 0028919 A1, in a U.S. Patent Nos. 7,741,319 B2, and WO 2011 / 130598 A1 and WO 2006 / 111759 A1, each of which is incorporated herein in its entirety by reference. A representative PBD number that has the following formula II can where: R2 is from Formula III: ^Q1 ^Q2 (III), where A is a C5-7 aryl group, X is a conjugated group with the connecting unit selected from the group consisting of —O—, —S—, —C(O)O—, —C(O)—, —NH(C=O)—, and —N(RN)—, wherein RN is selected from the group consisting of H, C1-4 alkyl and (C2H4O)mCH3, wherein m is between 1 and 3, and: (i) Q1 is a single bond, and Q2 is selected from the group consisting of a single bond and —Z—(CH2)n—, wherein Z is selected from the group consisting of a single bond, O, S and NH and n is between 1 and 3; or (ii) Q1 is —CH=CH—, and Q2 is a single bond; R12 is a C5-10 aryl group, optionally substituted with one or more substituents selected from the group consisting of halo, nitro, cyano, C1-12 alkoxy, C3-20 heterocycloalkoxy, C5-20 aryloxy, heteroaryloxy, alkylalkoxy, arylalkoxyl, alkylaryloxyl, heteroarylalkoxyl, alkylheteroaryloxyl, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene; R6 and R9 are selected independently from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NRR', nitro, Me3Sn and halo; wherein R and R' are independently selected from the group consisting of optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NHRR', nitro, Me3Sn and halo; one of: (a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are attached; or (c) R10 is H and R11 is SOzM, where z is 2 or 3; R" is a C3-12 alkylene group, whose chain may be interrupted by one or more heteroatoms, selected from the group consisting of O, S, NH, and an aromatic ring; Y and Y' are selected from the group consisting of O, S, and NH; R6', R7', R9' are selected from the same groups as R6, R7 and R9 respectively and R10' and R11' are the same as R10 and R11, and each M is a pharmaceutically acceptable monovalent cation or both M groups together are a pharmaceutically acceptable divalent cation. The phrase "optionally substituted" as used herein refers to a parent group that may be either not substituted or may be substituted. Unless otherwise specified, the term "substituted," as used herein, refers to a parent group bearing one or more substituents. The term "substituent" is used herein in the conventional sense and refers to a chemical group that is covalently bonded to, or, if appropriate, fused to, a parent group. A wide variety of substituents are well known, and the methods for their formation and introduction onto a variety of parent groups are also well known. C1-12 alkyl: The term "C1-12 alkyl," as used herein, refers to a monovalent portion obtained by the removal of a hydrogen atom from a carbon atom of a hydrocarbon compound having between 1 and 12 carbon atoms, which may be aliphatic or alicyclic, and which may be saturated or unsaturated (e.g., partially unsaturated, fully unsaturated). Therefore, the term "alkyl" includes the subclasses alkenyl, alkynyl, cycloalkyl, etc., as detailed below. Examples of saturated alkyl groups include, but are not limited to, methyl (C1), ethyl (C2), propyl (C3), butyl (C4), pentyl (C5), hexyl (C6), and heptyl (C7). Examples of saturated linear alkyl groups include, but are not limited to, methyl (C1), ethyl (C2), n-propyl (C3), n-butyl (C4), n-pentyl (amyl) (C5), n-hexyl (C6), and n-heptyl (C7). Examples of saturated branched alkyl groups include isopropyl (C3), isobutyl (C4), sec-butyl (C4), tert-butyl (C4), isopentyl (C5), and neopentyl (C5). C3-20 heterocyclyl: The term "C3-20 heterocyclyl" as used herein refers to a monovalent portion obtained by elimination of a hydrogen atom of a ring atom of a heterocyclic compound, wherein said portion has between 3 and 20 ring atoms, of which between 1 and 10 are ring heteroatoms. Preferably, each ring has between 3 and 7 ring atoms, of which between 1 and 4 are ring heteroatoms. In this context, the prefixes (e.g., C3-20, C3-7, C5-6, etc.) denote the number of ring atoms, or the range of the number of ring atoms, whether carbon atoms or heteroatoms. For example, the term "C5-6 heterocyclyl," as used herein, refers to a heterocyclyl group having 5 or 6 ring atoms. Examples of monocyclic heterocyclic groups include, by way of example only, those derived from: N1: aziridine (C3), azetidine (C4), pyrrolidine (tetrahydropyrrole) (C5), pyrroline (for example, 3-pyrroline, 2,5-dihydropyrrole) (C5), 2H-pyrrole or 3H-pyrrole (isopyrrole, isoazole) (C5), piperidine (C6), dihydropyridine (C6), tetrahydropyridine (C6), azepine (C7); O1: oxirane (C3), oxetane (C4), oxolane (tetrahydrofurano) (C5), oxol (dihydrofurano) (C5), oxano (tetrahydropyrano) (C6), dihydropyrano (C6), pyrano (C6), oxepina (C7); S1: thiirane (C3), thietane (C4), thiolane (tetrahydrothiophene) (C5), thiano (tetrahydrothiopyrano) (C6), thiepane (C7); O2: dioxolano (C5), dioxano (C6), and dioxepano (C7); O3: trioxano (C6); N2: imidazolidine (C5), pyrazolidine (diazolidine) (C5), imidazoline (C5), pyrazoline (dihydropyrazole) (C5), piperazine (C6); N1O1: tetrahydrooxazole (C5), dihydrooxazole (C5), tetrahydroisoxazole (C5), dihydroisoxazole (C5), morpholino (C6), tetrahydrooxazine (C6), dihydrooxazine (C6), oxazine (C6); N1S1: thiazoline (C5), thiazolidine (C5), thiomorpholino (C6); N2O1: oxadiazine (C6);O1S1: oxathiol (C5) and oxathane (thioxane) (C6); and, N1O1S1: oxathiazine (C6).; Examples of substituted monocyclic heterocyclic groups include those derived from saccharides, in cyclic form, for example, furanoses (C5), such as arabinofuranose, lixofuranose, ribofuranose, and xylofuranose, and pyranoses (C6), such as allopyranose, altropyranose, glucopyranose, mannopyranose, gulopyranose, idopyranose, galactopyranose, and talopyranose. C5-2 aryl: The term "C5-20 aryl", as used herein, refers to a monovalent portion obtained by the removal of a hydrogen atom from an aromatic ring atom of an aromatic compound, wherein said portion has between 3 and 20 ring atoms. Preferably, each ring has between 5 and 7 ring atoms. In this context, the prefixes (e.g., C3-20, C5-7, C5-6, etc.) indicate the number of ring atoms, or the range of the number of ring atoms, whether carbon atoms or heteroatoms. For example, the term "C5-6 aryl," as used herein, refers to an aryl group having 5 or 6 ring atoms. In one embodiment, the anti-EGFR antibodies of the invention can be conjugated with a PBD dimer having the following formula: wherein the preceding structure describes the PBD dimer SG2202 (ZC-207) and is conjugated to the anti-EGFR antibody of the invention via an L-connector. The SG2202 (ZC-207) is described in, for example, U.S. Patent Application Publication No. 2007 / 0173497, which is incorporated herein in its entirety by reference. In another embodiment, a PBD dimer, SGD-1882, is conjugated to the anti-EGFR antibody of the invention via a drug linker, as described in Figure 21. SGD-1882 is described in Sutherland et al. (2013) Blood 122(8):1455 and in U.S. Patent Application Publication No. 2013 / 0028919, which is incorporated herein in its entirety by reference. As described in Figure 21, the PBD dimer SGD-1882 can be conjugated to an antibody via an mc-val-ala-dipeptide linker (collectively referred to as SGD-1910 in Figure 21). In one embodiment, an anti-EGFR antibody, as described herein, is conjugated to the PBD dimer described in Figure 21. Therefore, in another embodiment, the invention includes an anti-EGFR antibody, as described herein, conjugated to a PBD dimer via an mc-val-ala-dipeptide linker, as described in Figure 21. In certain embodiments, the invention includes an anti-EGFR antibody comprising a heavy-chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 12, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 11, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 10, and a light-chain variable region comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 8, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 7, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 6, conjugated to a PBD, which includes, by way of example and not limitation, the number of PBDs described in Figure 21. In certain embodiments, the invention includes an anti-EGFR antibody comprising the a variable region of the AbA heavy chain as defined by its amino acid sequence detailed in SEQ ID NO: 9, and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 5, wherein the antibody is conjugated to a PBD, such as, by way of example only, the exemplary PBD dimer of Figure 21. b. Anthracyclines The anti-EGFR antibodies of the invention can be conjugated with at least one anthracycline. Anthracyclines are a subclass of antitumor antibiotics isolated from bacteria of the genus Streptomyces. Representative examples include, but are not limited to, daunorubicin (Cerubidin, Bedford Laboratories), doxorubicin (Adriamycin, Bedford Laboratories; also referred to as doxorubicin hydrochloride, hydroxydaunorubicin, and Rubex), epirubicin (Ellence, Pfizer), and idarubicin (Idamycin; Pfizer Inc.). Therefore, in one embodiment, the anti-EGFR antibody of the invention is conjugated with at least one anthracycline, for example, doxorubicin. c. Caliqueamycins The anti-EGFR antibodies of the invention can be conjugated with at least one caliqueamycin. Caliqueamycins are a family of enediin antibiotics derived from the soil organism Micromonospora echinospora. Caliqueamycins bind to the minor groove of DNA and induce double-strand DNA breakage, resulting in cell death with a 100-fold increase compared to other chemotherapeutic agents (Damle et al. (2003) Curr Opin Pharmacol 3:386). The preparation of caliqueamycins that can be used as drug conjugates in the invention has been described; see the patents. of the U.S. Nos. 5,712,374; 5,714,586; 5,739,116; 5,767,285; 5,770,701; 5,770,710; 5,773,001; and 5,877,296. The structural analogues of Caliqueamycins that may be used include, but are not limited to, YiI, a2I, a3I, N-acetyl-YiI, PSAG, and 9Ii (Hinman et al., Cancer Research 53:3336-3342 (1993), Lode et al., Cancer Research 58:2925-2928 (1998), and U.S. Patents Nos. 5,712,374; 5,714,586; 5,739,116; 5,767,285; 5,770,701; 5,770,710; 5,773,001; and 5,877,296, cited above). Therefore, in one embodiment, the anti-EGFR antibody of the invention is conjugated to at least one caliqueamycin. d. Duocarmycins The anti-EGFR antibodies of the invention can be conjugated with at least one duocarmycin. Duocarmycins are a subclass of antitumor antibiotics isolated from bacteria of the genus Streptomyces (see Nagamura and Saito (1998) Chemistry of Heterocyclic Compounds, Vol. 34, No. 12). Duocarmycins bind to the minor groove of DNA and alkylate the nucleobase adenine at the N3 position (Boger (1993) Pure and Appl Chem 65(6):1123; and Boger and Johnson (1995) PNAS USA 92:3642). Synthetic analogues of duocarmycins include, but are not limited to, adozelesin, bizelesin, and carzelesin. Therefore, in one embodiment, the anti-EGFR antibody of the invention is conjugated with at least one duocarmycin. e. Other antitumor antibiotics In addition to the above, additional antitumor antibiotics that may be used in the anti-EGFR ADCs of the invention include bleomycin (Blenoxane, Bristol-Myers Squibb), mitomycin, and plicamycin (also known as mithramycin). 3. Immunomodulatory agents In one aspect, the anti-EGFR antibodies of the invention can be conjugated with at least one immunomodulatory agent. As used herein, the term “immunomodulatory agent” refers to an agent that can stimulate or modify an immune response. In one embodiment, an immunomodulatory agent is an immunostimulant that enhances an immune response in a subject. In another embodiment, an immunomodulatory agent is an immunosuppressant that prevents or diminishes an immune response in a subject. An immunomodulatory agent can modulate myeloid cells (monocytes, macrophages, dendritic cells, megakaryocytes, and granulocytes) or lymphoid cells (T cells, B cells, and natural killer (NK) cells) and any more differentiated cells thereof. Representative examples include, but are not limited to, Bacillus Calmette-Guérin (BCG) and levamisole (Ergamisol).Other examples of immunomodulatory agents that can be used in the ADCs of the invention include, but are not limited to, cancer vaccines, cytokines, and immunomodulatory gene therapy. a. Cancer vaccines. The anti-EGFR antibodies of the invention can be conjugated to a cancer vaccine. As used herein, the term “cancer vaccine” refers to a composition (for example, a tumor antigen and a cytokine) that elicits a tumor-specific immune response. The response is elicited from the subject's own immune system by administration of the cancer vaccine, or, in the case of the present invention, by administration of an ADC comprising an anti-EGFR antibody and a cancer vaccine. In preferred embodiments, the immune response results as The result is the eradication of tumor cells in the body (e.g., primary or metastatic tumor cells). The use of cancer vaccines generally involves the administration of a particular antigen or group of antigens that are, for example, present on the surface of a particular cancer cell, or present on the surface of a particular infectious agent known to facilitate cancer formation. In some embodiments, the use of cancer vaccines has prophylactic purposes, while in other embodiments, the use has therapeutic purposes.Non-limiting examples of cancer vaccines that may be used in the anti-EGFR ADCs of the invention include recombinant bivalent human papillomavirus (HPV) vaccine types 16 and 18 (Cervarix, GlaxoSmithKline), recombinant quadrivalent human papillomavirus (HPV) vaccine types 6, 11, 16, and 18 (Gardasil, Merck & Company), and sipuleucel-T (Provenge, Dendreon). Therefore, in one embodiment, the anti-EGFR antibody of the invention is conjugated to at least one cancer vaccine that is either an immunostimulant or an immunosuppressant. b. Cytokines The anti-EGFR antibodies of the invention can be conjugated with at least one cytokine. The term “cytokine” generally refers to proteins released by a cell population that act on another cell as an intercellular mediator. Cytokines directly stimulate effector immune cells and stromal cells at the tumor site and enhance the recognition of the tumor cell by cytotoxic effector cells (Lee and Margolin (2011) Cancers 3:3856). Numerous studies in animal tumor models have demonstrated that cytokines have broad antitumor activity, and this has It has been used for different cytokine-based strategies for cancer therapy (Lee and Margoli, above). Recent years have seen a number of cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, and IL-21, enter clinical trials for patients with advanced cancer (Lee and Margoli, above). Examples of cytokines that may be used in the ADCs of the invention include, but are not limited to, parathyroid hormone; thyroxine; insulin; proinsulin; relaxin; prorelaxin; glycoprotein hormones such as follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and luteinizing hormone (LH); liver growth factor; fibroblast growth factor; prolactin; placental lactogen; tumor necrosis factor; Müllerian inhibitory substance; mouse gonadotropin-associated peptide; inhibin; activin; vascular endothelial growth factor; integrin; thrombopoietin (TPO); nerve growth factors such as NGF; platelet growth factor; transforming growth factors (TGF); insulin-like growth factor I and II; erythropoietin (EPO); bone-inducing factor; interferons such as interferon a, p, yy, colony-stimulating factors (CSF); granulocyte-macrophage-CSF (GM-CSF);and granulocyte-CSF (G-CSF); interleukins (ILs) such as IL-1, IL-1a, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-11, IL-12; tumor necrosis factor; and other polypeptide factors including LIF and the kit ligand (KL). As used herein, the term cytokine includes proteins from natural sources or recombinant cell cultures, and biologically equivalents of native cytokine sequences. Therefore, in one embodiment, the invention provides; an ADC comprising an anti-EGFR antibody written herein and a cytokine. c. Colony-stimulating factors (CSF) The anti-EGFR antibodies of the invention can be conjugated with at least one colony-stimulating factor (CSF). Colony-stimulating factors (CSFs) are growth factors that assist the bone marrow in producing red blood cells. Because some cancer treatments (e.g., chemotherapy) can affect white blood cells (which help fight infection), colony-stimulating factors can be introduced to help maintain white blood cell levels and strengthen the immune system. Colony-stimulating factors can also be used after a bone marrow transplant to help the new marrow initiate white blood cell production. Representative examples of CSFs that can be used in the anti-EGFR ADCs of the invention include, but are not limited to, erythropoietin (Epoetin), filgrastim (Neopogen, also known as granulocyte colony-stimulating factor (G-CSF)); Amgen, Inc.), sargramostim (leukin (granulocyte-macrophage colony-stimulating factor and GM-CSF); Genzima Corporation), promegapoietin, and Oprelvekin (recombinant IL-11; Pfizer, Inc.). Therefore, in one embodiment, the invention provides an ADC comprising an anti-EGFR antibody described herein and a CSF. 4. Gene therapy The anti-EGFR antibody of the invention can be conjugated to at least one nucleic acid (directly or indirectly via a carrier) for gene therapy. Gene therapy generally refers to the introduction of Genetic material in a cell where the genetic material is engineered to treat a disease. With regard to immunomodulatory agents, gene therapy is used to stimulate a subject's natural ability to inhibit the proliferation of cancer cells or to kill cancer cells. In one embodiment, the anti-EGFR ADC of the invention comprises a nucleic acid encoding a functional, therapeutic gene used to replace a mutated or otherwise (e.g., truncated) gene associated with cancer. In other embodiments, the anti-EGFR ADC of the invention comprises a nucleic acid encoding or otherwise providing for the production of a therapeutic protein for treating cancer. The nucleic acid encoding the therapeutic gene can be directly conjugated to the anti-EGFR antibody, or alternatively, it can be conjugated to the anti-EGFR antibody via a carrier.Examples of carriers that can be used to deliver a nucleic acid for gene therapy include, but are not limited to, viral vectors or liposomes. 5. Alkylating agents The anti-EGFR antibodies of the invention can be conjugated with one or more alkylating agents. Alkylating agents are a class of antineoplastic compounds that attach an alkyl group to DNA. Examples of alkylating agents that can be used in the ADCs of the invention include, but are not limited to, alkyl sulfonates, ethyleneimimes, methylamine derivatives, epoxides, nitrogen mustards, nitrosoureas, triazines, and hydrazines. a. Alkyl sulfonates The anti-EGFR antibodies of the invention can be conjugated with at least one alkyl sulfonate. Alkyl sulfonates are a subclass of alkylating agents with the general formula R-SO2-O-R1, where R and R1 are typically alkyl or aryl groups. A representative example of an alkyl sulfonate includes, but is not limited to, busulfan (Milerano, GlaxoSmithKline; Busulfex IV, PDL BioPharma, Inc.). b. Nitrogen mustards The anti-EGFR antibodies of the invention can be conjugated with at least one nitrogen mustard. Representative examples of this subclass of anticancer compounds include, but are not limited to, chlorambucil (Leukeran, GlaxoSmithKline), cyclophosphamide (Cytoxane, Bristol-Myers Squibb; Neosar, Pfizer, Inc.), estramustine (estramustine sodium phosphate or Estracyt, Pfizer, Inc.), ifosfamide (Ifex, Bristol-Myers Squibb), mechlorethamine (Mustargen, Lundbeck Inc.), and melphalan (Alkeran or L-Pam or phenylalanine mustard; GlaxoSmithKline). c. Nitrosoureas The anti-EGFR antibody of the invention can be conjugated with at least one nitrosourea. Nitrosoureas are a subclass of lipid-soluble alkylating agents. Representative examples include, but are not limited to, carmustine (BCNU [also known as BiCNU, N,N-Bis(2-chloroethyl)-N-nitrosourea, or 1,3-bis(2-chloroethyl)-1-nitrosourea], Bristol-Myers Squibb), fotemustine (also known as Muforan), lomustine (CCNU or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, Bristol-Myers Squibb), nimustine (also known as ACNU), and streptozocin (Zanosar, Teva Pharmaceuticals). d. Triazines and Hydrazines The anti-EGFR antibody of the invention can be conjugated with at least one triazine or hydrazine. Triazines and hydrazines are a subclass of nitrogen-containing alkylating agents. In some embodiments, these compounds spontaneously decompose or can be metabolized to produce alkyl diazonium intermediates that facilitate the transfer of an alkyl group to nucleic acids, peptides, and / or polypeptides, thereby causing mutagenic, carcinogenic, or cytotoxic effects. Representative examples include, but are not limited to, dacarbazine (DTIC-Dome, Bayer Healthcare Pharmaceuticals Inc.), procarbazine (Mutalano, Sigma-Tau Pharmaceuticals, Inc.), and temozolomide (Temodar, Schering Plough). e. Other renting agents The anti-EGFR antibodies of the invention can be conjugated with at least one ethyleneimine, methylamine derivative, or epoxide. Ethyleneimines are a subclass of alkylating agents that typically contain at least one aziridine ring. Epoxies represent a subclass of alkylating agents characterized as cyclic ethers with only three ring atoms. Representative examples of ethyleneimines include, but are not limited to, thiopeta (Tioplex, Amgen), diaziquone (also known as aziridinyl benzoquinone (AZQ)), and mitomycin C. Mitomycin C is a naturally occurring product containing an aziridine ring and appears to induce cytotoxicity by DNA cross-linking (Dorr RT, et al. Cancer Res. 1985;45:3510; Kennedy KA, et al. Cancer Res. 1985;45:3541). Representative examples of methylamine derivatives and their analogues include, but are not limited to, altretamine (Hexalen, MGI Pharma, Inc.), which is also known as Hexamethylamine and hexastat. Representative examples of epoxides in this class of anticancer compounds include, but are not limited to, dianhydrogalactitol. Dianhydrogalactitol (1,2:5,6-dianhydrodulcitol) is chemically related to aziridines and generally facilitates the transfer of an alkyl group through a mechanism similar to that described above. Dibrodulcitol is hydrolyzed to dianhydrogalactitol and is therefore a prodrug of an epoxide (Sellei C, et al. Cancer Chemother Rep. 1969;53:377). 6. Antiangiogenic agents In one aspect, the anti-EGFR antibodies described herein are conjugated to at least one antiangiogenic agent. Antiangiogenic agents inhibit the growth of new blood vessels. They exert their effects in a variety of ways. In some embodiments, these agents interfere with a growth factor's ability to reach its target. For example, vascular endothelial growth factor (VEGF) is one of the main proteins involved in initiating angiogenesis by binding to specific receptors on a cell surface. Therefore, certain antiangiogenic agents, which prevent VEGF from interacting with its related receptor, prevent VEGF from initiating angiogenesis. In other embodiments, these agents interfere with intracellular signaling cascades.For example, once a particular receptor on a cell surface has been stimulated, a cascade of other chemical signals is initiated to promote blood vessel growth. Therefore, certain enzymes, such as some tyrosine kinases, are known to facilitate these intracellular signaling cascades. Substances that contribute to, for example, cell proliferation, are targets of cancer treatment. In other formulations, these agents interfere with intercellular signaling cascades. Furthermore, in other formulations, these agents inactivate specific targets that activate and promote cell growth or directly interfere with the growth of blood vessel cells. Angiogenesis-inhibiting properties have been discovered for more than 300 substances with numerous direct and indirect effects. Representative examples of antiangiogenic agents that may be used in the ADCs of the invention include, but are not limited to, angiostatin, ABX EFG, C1-1033, PKI-166, EGF vaccine, EKB-569, GW2016, ICR-62, EMD 55900, CP358, PD153035, AG1478, IMC-C225 (Erbitux, ZD1839 (Iressa), OSI-774, Erlotinib (tarceva), angiostatin, arrestin, endostatin, BAY 12-9566 and with fluorouracil or doxorubicin, canstatin, carboxyamidotriozole and with paclitaxel, EMD121974, S-24, vitaxin, dimethylxanthenone acetic acid, IM862, Interleukin-12, Interleukin-2, NM-3, HuMV833, PTK787, RhuMab, angiozyme (ribozyme), IMC-1C11, Neovastat, marimstat, prinomastat, BMS-275291,COL-3, MM1270, SU101, SU6668, SU11248, SU5416, with paclitaxel, with gemcitabine and cisplatin, and with irinotecan and cisplatin and with radiation, tecogalan, temozolomide and interferon a2b treated with PEG, tetrathiomolybdate, TNP-470, thalidomide, CC-5013 and with taxotere, tumstatin, 2-methoxyestradiol, VEGF sequestrant, mTOR inhibitors (deforolimus, everolimus (Afinitor, Novartis Pharmaceutical Corporation), and temsirolimus (Torisel, Pfizer, Inc.)), tyrosine kinase inhibitors (eg, erlotinib (Tarceva, Genentech, Inc.), imatinib (Gleevec, Novartis Pharmaceutical). Corporation, gefitinib (Iressa, AstraZeneca Pharmaceuticals), dasatinib (Sprycel, Brystol-Myers Squibb), sunitinib (Sutent, Pfizer, Inc.), nilotinib (Tasigna, Novartis Pharmaceutical Corporation), lapatinib (Tykerb, GlaxoSmithKline Pharmaceuticals), and sorafenib (Nexavar, Bayer, Inc.). Onyx), phosphoinositol 3-kinases (PI3K). 7. Antimetabolites The anti-EGFR antibodies of the invention can be conjugated with at least one antimetabolite. Antimetabolites are types of chemotherapeutic treatments that are very similar to normal substances within the cell. When cells incorporate an antimetabolite into their cellular metabolism, the result is detrimental to the cell; for example, the cell becomes unable to divide. Antimetabolites are classified according to the substances with which they interfere.Examples of antimetabolites that may be used in the ADCs of the invention include, by way of example and not limitation, a folic acid antagonist (e.g., methotrexate), a pyrimidine antagonist (e.g., 5-Fluorouracil, Foxuridine, Cytarabine, Capecitabine, and Gemcitabine), a purine antagonist (e.g., 6-Mercaptopurine and 6-Thioguanine), and an adenosine deaminase inhibitor (e.g., Cladribine, Fludarabine, Nelarabine, and Pentostatin), as described in more detail below. a. Antifolates The anti-EGFR antibodies of the invention can be conjugated with at least one antifolate. Antifolates are a subclass of antimetabolites that are structurally similar to folate. Representative examples include, but are not limited to, methotrexate, 4-aminofolic acid (also known as aminopterin and 4-aminopteroic acid), lometrexol (LMTX), pemetrexed (Alimpta, Eli Lilly and Company), and trimetrexate (Neutrexin, Ben Venue Laboratories, Inc.). b. Purine antagonists The anti-EGFR antibodies of the invention can be conjugated with at least one purine antagonist. Purine analogs are a subclass of antimetabolites that are structurally similar to the group of compounds known as purines. Representative examples of purine antagonists include, but are not limited to, azathioprine (Azasan, Salix; Imuran, GlaxoSmithKline), cladribine (Leustatin [also known as 2-CdA], Janssen Biotech, Inc.), mercaptopurine (Purinethol [also known as 6-mercaptoethanol], GlaxoSmithKline), fludarabine (Fludara, Genzima Corporation), pentostatin (Nipent, also known as 2'-deoxyformicin (DCF)), and 6-thioguanine (Lanvis [also known as thioguanine], GlaxoSmithKline). c. Pyrimidine antagonists The anti-EGFR antibodies of the invention can be conjugated with at least one pyrimidine antagonist. Pyrimidine antagonists are a subclass of antimetabolites that are structurally similar to the group of compounds known as pyrimidines. Representative examples of pyrimidine antagonists include, but are not limited to, azacitidine (Vidaza, Celgene Corporation), capecitabine (Xeloda, Roche Laboratories), cytarabine (also known as cytosine arabinoside and arabinosylcytosine, Bedford Laboratories), decitabine (Dacogen, Eisai Pharmaceuticals), and 5-fluorouracil (Adrucil, Teva Pharmaceuticals; Efudex, Valeant Pharmaceuticals). Inc), 5-fluoro-2'-deoxyuridine 5'-phosphate (FdUMP), 5-fluorouridine triphosphate, and gemcitabine (Gemzar, Eli Lilly and Company). 8. Agents containing boron The anti-EGFR antibody of the invention can be conjugated with at least one boron-containing agent. Boron-containing agents comprise a class of cancer therapeutics that interfere with cell proliferation. Representative examples of boron-containing agents include, but are not limited to, borophycin and bortezomib (Velcade, Millennium Pharmaceuticals). 9. Chemoprotective agents The anti-EGFR antibodies of the invention can be conjugated with at least one chemoprotective agent. Chemoprotective drugs are a class of compounds that help protect the body against specific toxic effects of chemotherapy. Chemoprotective agents can be administered with different chemotherapies to protect healthy cells from the toxic effects of the chemotherapy drugs, while simultaneously allowing cancer cells to be treated with the administered chemotherapy. Representative chemoprotective agents include, but are not limited to, amifostine (Etiol, Medimmune, Inc.).), which is used to reduce renal toxicity associated with cumulative doses of cisplatin, dexrazoxane (Totect, Apricus Pharma; Zinecard), for the treatment of extravasation caused by the administration of anthracycline (Totect), and for the treatment of heart-related complications caused by the administration of the antitumor antibiotic doxorubicin (Zinecard), and mesna. (Mesnex, Bristol-Myers Squibb), which is used to prevent hemorrhagic cystitis during chemotherapy treatment with ifocfamide. 10. Hormonal agents The anti-EGFR antibody of the invention can be conjugated with at least one hormonal agent. A hormonal agent (including synthetic hormones) is a compound that interferes with the production or activity of endogenously produced hormones of the endocrine system. In some embodiments, these compounds interfere with cell growth or produce a cytotoxic effect. Non-limiting examples include androgens, estrogens, medroxyprogesterone acetate (Provera, Pfizer, Inc.), and progestins. 11. Antihormonal agents The anti-EGFR antibodies of the invention can be conjugated with at least one antihormonal agent. An “antihormonal” agent is an agent that suppresses the production of and / or prevents the function of certain endogenous hormones. In one embodiment, the antihormonal agent interferes with the activity of a hormone selected from the group comprising androgens, estrogens, progesterone, and gonadotropin-releasing hormone, thereby interfering with the growth of various cancer cells. Representative examples of antihormonal agents include, but are not limited to, aminoglutethimide, anastrozole (Arimidex, AstraZeneca Pharmaceuticals), bicalutamide (Casodex, AstraZeneca Pharmaceuticals), cyproterone acetate (Cyprostat, Bayer PLC), degarelix (Firmagon, Ferring Pharmaceuticals), exemestane (Aromasina, Pfizer Inc.), flutamide (Drogenilo, Schering-Plough Ltd), fulvestrant (Faslodex, AstraZeneca Pharmaceuticals), goserelin (Zolodex, AstraZeneca Pharmaceuticals), letrozole (Femara, Novartis Pharmaceuticals Corporation), leuprolide (Prostap), lupron, medroxyprogesterone acetate (Provera, Pfizer Inc.), megestrol acetate (Megace, Bristol-Myers Squibb Company), tamoxifen (Nolvadex, AstraZeneca Pharmaceuticals), and triptorelin (Decapetil, Ferring). 12. Corticosteroids The anti-EGFR antibodies of the invention can be conjugated with at least one corticosteroid. Corticosteroids can be used in the ADCs of the invention to reduce inflammation. An example of a corticosteroid includes, but is not limited to, a glucocorticoid, for example, prednisone (Deltasona, Pharmacia & Upjohn Company, a division of Pfizer, Inc.). 13. Photoactive therapeutic agents The anti-EGFR antibodies of the invention can be conjugated with at least one photoactive therapeutic agent. Photoactive therapeutic agents include compounds that can be used to kill cells treated with electromagnetic radiation exposure of a particular wavelength. Therapeutically relevant compounds absorb electromagnetic radiation at wavelengths that penetrate tissue. In preferred embodiments, the compound is administered in a non-toxic form that has the ability to produce a photochemical effect that is toxic to cells or tissue when sufficiently activated. In other preferred embodiments, these compounds are retained by cancerous tissue and are readily excluded from normal tissues. Non-limiting examples include various chromogens and dyes. 14. Oligonucleotides The anti-EGFR antibodies of the invention can be conjugated to at least one oligonucleotide. Oligonucleotides are short chains of nucleic acid that function by interfering with the processing of genetic information. In some embodiments, the oligonucleotides for use in the ADCs are unmodified single-stranded and / or double-stranded DNA or RNA molecules, while in other embodiments, these therapeutic oligonucleotides are chemically modified single-stranded and / or double-stranded DNA or RNA molecules. In one embodiment, the oligonucleotides used in the ADCs are relatively short (between 19 and 25 nucleotides) and hybridize to a single nucleic acid sequence within the total set of nucleic acid targets present in cells. Some of the important oligonucleotide technologies include antisense oligonucleotides (including interfering RNA (RNAi)), aptamers, CpG oligonucleotides, and ribozymes. to. Antisense oligonucleotides The anti-EGFR antibody of the invention can be conjugated to at least one antisense oligonucleotide. The antisense oligonucleotides are designed to bind to RNA by Watson-Crick hybridization. In some embodiments, the antisense oligonucleotide is complementary to a polynucleotide encoding a region, domain, portion, or segment of EGFR. In some embodiments, the antisense oligonucleotide comprises from approximately 5 to approximately 100 nucleotides, from approximately 10 to approximately 50 nucleotides, from approximately 12 to approximately 35 nucleotides, and from approximately 18 to approximately 25 nucleotides. In some embodiments, the An oligonucleotide is at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 100% homologous to a region, portion, domain, or segment of the EGFR gene. In some embodiments, there is substantial sequence homology in at least 15, 20, 25, 30, 35, 40, 50, or 100 consecutive nucleotides of the EGFR gene. In preferred embodiments, the size of these antisense oligonucleotides ranges from 12 to 25 nucleotides in length, with the majority of antisense oligonucleotides being between 18 and 21 nucleotides in length. There are multiple mechanisms that can be exploited to inhibit RNA function once the oligonucleotide binds to the target RNA (Crooke ST. (1999). Biochim. Biophys. Acta, 1489, 30-42).The best-characterized antisense mechanism results in the cleavage of the target RNA by endogenous cellular nucleases, such as RNase H or the nuclease associated with the RNA interference mechanism. However, oligonucleotides that inhibit target gene expression through non-catalytic mechanisms, such as modulation of the splicing mechanism or translation arrest, can also be potent and selective modulators of gene function. Another RNase-dependent antisense mechanism that has recently received much attention is RNAi (Fire et al. (1998). Nature, 391, 806-811; Zamore PD. (2002). Science, 296, 1265-1269). RNA interference (RNAi) is a post-transcriptional process in which a double-stranded RNA inhibits gene expression in a sequence-specific manner. In some embodiments, the effect of RNAi is achieved by the introduction of a relatively longer double-stranded RNA (dsRNA), while inIn preferred embodiments, this effect of RNAi is achieved by introducing shorter double-stranded RNAs, such as small interfering RNA (pRNA) and / or microRNA (miRNA). In yet another embodiment, RNAi can be obtained by introducing a plasmid that generates dhRNA complementary to the target gene. In each of the preceding embodiments, the double-stranded RNA is designed to interfere with the gene expression of a particular target sequence in cells. Generally, the mechanism involves the conversion of dhRNA to short cRNAs that direct ribonucleases to homologous mRNA targets (summarized in Ruvkun, Science 2294:797 (2001)), which then degrade the corresponding endogenous mRNA, thereby modulating gene expression. Notably, RNAdh has been reported to have antiproliferative properties, which also makes it possible to plan therapeutic applications (Aubel et al., Proc. Natl. Acad. Sci., USA 88:906 (1991)).For example, synthetic dhRNA has been shown to inhibit tumor growth in mice (Levy et al., Proc. Nat. Acad. Sci. USA, 62:357-361 (1969)), is active in the treatment of leukemic mice (Zeleznick et al., Proc. Soc. Exp. Biol. Med. 130:126-128 (1969)), and inhibits chemically induced tumorigenesis in mouse skin (Gelboin et al., Science 167:205-207 (1970)). Therefore, in a preferred embodiment, the invention provides for the use of antisense oligonucleotides in ADCs for the treatment of breast cancer. In other embodiments, the invention provides compositions and methods for initiating treatment with antisense oligonucleotides, wherein the RNAdh interferes with the expression of EGFR in target cells at the mRNA level. The RNAdh, as used above, refers to a naturally occurring RNA, partially purified RNA, recombinantly produced RNA, synthetic RNA, as well as RNA. altered RNA that differs from naturally occurring RNA by the inclusion of non-standard nucleotides, non-nucleoside material, nucleotide analogs (e.g., blocked nucleic acid (LNA)), deoxyribonucleotides, and any combination thereof. The NA RNA of the invention need only be sufficiently similar to natural RNA that has the ability to mediate modulation based on the antisense oligonucleotide described herein. b. Aptamers The anti-EGFR antibodies of the invention can be conjugated to at least one aptamer. An aptamer is a nucleic acid molecule that has been randomly selected from a pool based on its ability to bind to other molecules. Like antibodies, aptamers can bind to target molecules with extraordinary affinity and specificity. In many embodiments, aptamers assume complex, sequence-dependent, three-dimensional shapes that enable them to interact with a target protein, resulting in a tightly bound complex analogous to an antibody-antigen interaction, thereby interfering with the function of that protein. The particular ability of aptamers to bind tightly and specifically to their target protein underscores their potential as targeted molecular therapies. c. CpG Oligonucleotides The anti-EGFR antibodies of the invention can be conjugated with at least one CpG oligonucleotide. Bacterial and viral DNA are known to be strong activators of innate and specific immunity in humans. These immunological characteristics have been associated with unmethylated CpG dinucleotide motifs found in bacterial DNA. Due to the fact that these These motifs are unusual in humans, but the human immune system has evolved to recognize them as an early indicator of infection and subsequent initiation of immune responses. Therefore, oligonucleotides containing this CpG motif can be harnessed to initiate an antitumor immune response. d. Ribozymes The anti-EGFR antibody of the invention can be conjugated with at least one ribozyme. Ribozymes are catalytic RNA molecules that range in length from approximately 40 to 155 nucleotides. The ability of ribozymes to recognize and cleave specific RNA molecules makes them potential therapeutic candidates. A representative example is angiozyme. 15. Radionuclide agents (radioactive isotopes) The anti-EGFR antibodies of the invention can be conjugated with at least one radionuclide. Radionuclides comprise agents characterized by an unstable nucleus capable of undergoing radioactive decay. Successful radionuclide treatment depends on a sufficient concentration and prolonged retention of the radionuclide by the cancer cell. Other factors to consider include the radionuclide's half-life, the energy of the emitted particles, and the maximum range the emitted particle can travel. In preferred embodiments, the therapeutic agent is a radionuclide selected from the group consisting of 111In, 177Lu, 212Bi, 213Bi, 211At, 62Cu, 64Cu, 67Cu, 90Y, I25I, I31I, 32P, 33P, 47Sc, 111Ag, 67Ga, 142Pr, 153Sm, 161Tb, 166Dy, 166Ho, 186Re, 188Re, 189Re, 212Pb, 223Ra, 225Ac, 59Fe, 75Se, 77As, 89Sr, 99Mo, 105Rh, I09Pd, 143Pr, 149Pm, 169Er, 194Ir, 198Au, 199Au, and 211Pb. Radionuclides that decay substantially with Auger-emitting particles are also preferred. Examples include Co-58, Ga-67, Br-80m, Tc-99m, Rh-103m, Pt-109, In-111, Sb-119, I-125, Ho-161, Os-189m, and Ir-192. The decay energies of useful nuclides that preferentially emit beta particles are Dy-152, At-211, Bi-212, Ra-223, Rn-219, Po-215, Bi-211, Ac-225, Fr-221, At-217, Bi-213, and Fm-255. The decay energies of useful nuclides that emit alpha particles preferentially are between 2,000 and 10,000 keV, more preferably between 3,000 and 8,000 keV, and even more preferably between 4,000 and 7,000 keV. Additional potential radioisotopes for use include 11C, 13N, 150, 75Br, 198Au, 224Ac, 126I, 133I, 77Br, 113mIn, 95Ru, 97Ru, 103Ru, 105Ru, 107Hg, 203Hg, 121mTe, 122mTe, 125mTe, 165Tm, 167Tm, 168Tm, 197Pt, 109Pd, 105Rh, 142Pr, 143Pr, 161Tb, 166Ho, 199Au, 57Co, 58Co, 51Cr, 59Fe, 75Se, 201Tl, 225Ac, 76Br. I69Yb, and similar. 16. Radiosensitizers The anti-EGFR antibodies of the invention can be conjugated with at least one radiosensitizer. The term “radiosensitizer,” as used herein, is defined as a molecule, preferably a low molecular weight molecule, administered to animals in therapeutically effective amounts to increase the sensitivity of cells to be radiosensitized to electromagnetic radiation and / or to promote the treatment of diseases that can be treated with electromagnetic radiation. Radiosensitizers are agents that make cancer cells more sensitive to radiation therapy, while typically having much less effect on a normal cell. Therefore, the radiosensitizer can be used in combination with a radiolabeled antibody or ADC. The addition of the radiosensitizer can Radiosensitizers offer improved efficacy compared to treatment with the radiolabeled antibody or antibody fragment alone. They are described in DM Goldberg (ed.), Cancer Therapy with Radiolabeled Antibodies, CRC Press (1995). Examples of radiosensitizers include gemcitabine, 5-fluorouracil, taxane, and cisplatin. Radiosensitizers can be activated by electromagnetic radiation from X-rays. Representative examples of X-ray-activated radiosensitizers include, but are not limited to, the following: metronidazole, misonidazole, desmethylmisonidazole, pimonidazole, etanidazole, nimorazole, mitomycin C, RSU 1069, SR 4233, E09, RB 6145, nicotinamide, 5-bromodeoxyuridine (BUdR), 5-iododeoxyuridine (IUdR), bromodeoxycytidine, fluorodeoxyuridine (FUdR), hydroxyurea, cisplatin, and therapeutically effective analogues and derivatives thereof. Alternatively, radiosensitizers can be activated using photodynamic therapy (PDT).Representative examples of photodynamic radiosensitizers include, but are not limited to, hematoporphyrin derivatives, photophrine(r), benzoporphyrin derivatives, NPe6, stanoethioporphyrin (SnET2), pheoborbide a, bacteriochlorophyll a, naphthalocyanines, phthalocyanines, zinc phthalocyanines, and therapeutically effective analogues and derivatives thereof. 17. Topoisomerase inhibitors The anti-EGFR antibodies of the invention can be conjugated with at least one topoisomerase inhibitor. Topoisomerase inhibitors are chemotherapeutic agents designed to interfere with the action of topoisomerase enzymes (topoisomerase I and II), which are enzymes that control the Changes in DNA structure, or catalysis and subsequent breakage and reassembly of the phosphodiester backbone of DNA strands during the normal cell cycle. Representative examples of DNA topoisomerase I inhibitors include, but are not limited to, camptothecins and their derivatives irinotecan (CPT-11, Camptosar, Pfizer, Inc.) and topotecan (Hicamtine, GlaxoSmithKline Pharmaceuticals). Representative examples of DNA topoisomerase II inhibitors include, but are not limited to, amsacrine, daunorubicin, doxotrubicin, epipodophyllotoxins, ellipticins, epirubicin, etoposide, razoxane, and teniposide. 18. Tyrosine kinase inhibitors The anti-EGFR antibodies of the invention can be conjugated to at least one tyrosine kinase inhibitor. Tyrosine kinases are cellular enzymes that attach phosphate groups to the amino acid tyrosine. By blocking the ability of protein tyrosine kinases to function, tumor growth can be inhibited. Examples of tyrosine kinases that can be used in the anti-EGFR antibodies of the invention include, but are not limited to, axitinib, bosutinib, cediranib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, semaxanib, sunitinib, and vandetanib. 19. Other agents Examples of other agents that may be used in the ADCs of the invention include, but are not limited to, abrin (e.g., abrin A chain), alpha toxin, Aleurites fordii proteins, amatoxin, crotin, curcin, diantin proteins, diphtheria toxin (e.g., diphtheria A chain and diphtheria toxin non-binding active fragments), deoxyribonuclease (DNase), gelonin, mitogelin, modecin A chain, Momordica charantia inhibitor, neomycin, onconase, fenomycin, Phytolaca americana proteins (PAPI, PAPII, and PAPS), phytolaca antiviral protein, Pseudomonas endotoxin, Pseudomonas exotoxin (e.g., exotoxin A chain (from Pseudomonas aeruginosa)), restrictocin, ricin A chain, ribonuclease (RNase), Saponaria officinalis inhibitor, saporin, alpha-sarcin, staphylococcal enterotoxin-A, tetanus toxin, cisplatin, carboplatin, and oxaliplatin (Eloxatino, Sanofi Aventis), proteasome inhibitors (e.g., PS-341 [bortezomib or Velcade]), HDAC inhibitors (vorinostat (Zolinza, Merck & Company, Inc.)), belinostat, entinostat, mocetinostat, and panobinostat), inhibitors of COX-2 inhibitors, substituted ureas, heat shock protein inhibitors (e.g., geldanamycin and its numerous analogues), adrenocortical suppressants, and trichothecenes. (See, for example, WO 93 / 21232). Other agents also included are asparaginase (Espar, Lundbeck Inc.).), hydroxyurea, levamisole, mitotane (Lysodren, Bristol-Myers Squibb), and tretinoin (Renova, Valeant Pharmaceuticals Inc.). It should be noted that the aforementioned groups of pharmacological groups that can be used in the anti-EGFR ADCs of the invention are not exclusive, in that certain examples of drugs may be found in more than one category, for example, ansamitokines are mitotic inhibitors and antitumor antibiotics. All stereoisomers of the preceding pharmacological groups are contemplated for the compounds of the invention, i.e. any combination of R and S configurations on the chiral carbons of D. The preceding agents (i.e., bare agents not conjugated to an antibody) can also be used in combination therapies with the Anti-EGFR antibodies described herein. In one embodiment, anti-EGFR or ADC antibodies are used with any of the preceding agents in a combination therapy to treat cancer, wherein the agent is administered before, at the same time, or after the administration of the anti-EGFR or ADC antibody to the subject. B. ADC anti-EGFR: illustrative connectors An anti-EGFR ADC comprises an anti-EGFR antibody and at least one drug, wherein the antibody and the at least one drug are conjugated by a connector. The term “connector,” as used herein, refers to a chemical portion that may be bifunctional or multifunctional and is used to link an antibody to a drug group. A connector may include a single conjugation component or multiple components. For example, the connector may include a spacer, which is a portion that extends the drug binding to prevent, for example, the antibody's active site from being obscured or to improve the ADC's solubility. Other examples of connector components include an elongating unit and an amino acid unit. Two methods are commonly used to conjugate drugs to antibodies: alkylation of reduced interchain cysteines by means of a maleimide linker that cannot be enzymatically cleaved or a simple disulfide that can be cleaved, and acylation of lysines by linear amino acids that can be cleaved. In one respect, a connector covalently links an antibody to a drug group. An ADC is prepared using a connector that has reactive functionality for binding to both the antibody and the drug. For example, a cysteine ​​thiol, or an amine. For example, amino acid side chains such as lysine or the N-terminal end of the antibody can form a bond with a functional group of the connector. In one respect, a connective has a functionality that allows it to react with a free cysteine ​​present in an antibody to form a covalent bond. Non-limiting examples of such reactive functionalities include maleimide, haloacetamides, α-haloacetyl, activated esters such as succinimide esters, 4-nitrophenyl esters, pentafluorophenyl esters, tetrafluorophenyl esters, anhydrides, acid chlorides, sulfonyl chlorides, isocyanates, and isothiocyanates. See, for example, the conjugation method on page 766 of Klussman et al. (2004), Bioconjugate Chemistry 15(4):765-773. In some embodiments, a connective has a functionality that allows it to react with an electrophilic group present in an antibody. Examples of such electrophilic groups include, but are not limited to, carbonyl groups of aldehydes and ketones. In some embodiments, a heteroatom of the connective's reactive functionality can react with an electrophilic group in an antibody and form a covalent bond with an antibody unit. Examples of such reactive functionalities include, but are not limited to, hydrazide, oxime, amino, hydrazine, thiosemicarbazone, hydrazine carboxylate, and arylhydrazide. Exemplary connecting components include 6-maleimidocaproyl, maleimidopropanoyl (“MP”), valine-citrulline (“val-cit” or “vc”), alanine-phenylalanine (“ala-phe”), p-aminobenzyloxycarbonyl (a “PAB”), N- Succinimidyl 4-(2-pyridylthio)pentanoate (“SPP”), and 4-(N- maleimidomethyl)cyclohexane-1 (“MCC”). In one aspect, an anti-EGFR antibody is conjugated to an auristatin, for example, MMAE, via a connector comprising maleimidocaproyl (“mc”), valine citrulline (val-cit or “vc”), and PABA (referred to as an “mc-vc-PABA connector”). The maleimidocaproyl acts as a connector with the anti-EGFR antibody and cannot be cleaved. Val-cit is a dipeptide that is an amino acid unit of the connector and allows the connector to be cleaved by a protease, specifically cathepsin B protease. Thus, the val-cit component of the connector provides a means to release auristatin from the ADC when it is exposed to the intracellular environment. In the connector, the p-aminobenzyl alcohol (PABA) acts as a spacer and is self-cleaving, allowing the release of MMAE. The structure of the mc-vc-PABA-MMAE connector is provided in Figure 11. Suitable connectives include, for example, cleavable and non-cleavable connectives. A connective may be a “cleavable connective,” facilitating the release of a drug. Non-limiting examples of cleavable connectives include acid-labile connectives (e.g., comprising a hydrazone), protease-sensitive connectives (e.g., peptidase-sensitive), photolabile connectives, or disulfide-containing connectives (Chari et al., Cancer Research 52:127-131 (1992); U.S. Patent No. 5,208,020). A cleavable connective is typically susceptible to cleavage under intracellular conditions. Suitable cleavable connectives include, for example, a peptide connective that can be cleaved by an intracellular protease, such as lysosomal protease or an endosomal protease. In exemplary embodiments, the linker may be a dipeptide linker, such as a valine-citrulline (val-cit) or a phenylalanine-lysine (phe-lys) linker. The connectors are preferentially stable extracellularly to a degree sufficient to be therapeutically effective. Before transport or delivery to the cell, the ADC is preferentially stable and remains intact; that is, the antibody remains conjugated to the drug group. Connectors that are stable outside the target cell can be cleaved at some effective rates once inside the cell. Therefore, an effective connector will: (i) maintain the specific binding properties of the antibody; (ii) allow for the delivery, e.g., intracellular delivery, of the drug group; and (iii) maintain the therapeutic effect, e.g., cytotoxic effect, of the drug group. In one embodiment, the connector can be cleaved under intracellular conditions, such that cleavage of the connector releases sufficient drug from the antibody into the intracellular environment to be therapeutically effective. In some embodiments, the cleavable connector is pH-sensitive, i.e., susceptible to hydrolysis at different pH values. Typically, the pH-sensitive connector can be hydrolyzed under acidic conditions. For example, an acid-labile connector that can be hydrolyzed in the lysosome can be used (e.g., a hydrazone, semicarbazone, thiosemicarbazone, cis-aconoxyamide, orthoester, acetal, ketal, or similar). (See, for example, U.S. Patents Nos. 5,122,368; 5,824,805; 5,622,929; Dubowchik and Walker, 1999, Pharm. Therapeutics 83:67-123; Neville et al., 1989, Biol. Chem. 264:14653-14661). Such connectors are relatively stable under pH conditions neutral, such as those in the blood, but are unstable below a pH of 5.5 or 5.0, the approximate pH of the lysosome. In certain embodiments, the connective that can be hydrolyzed is a thioether connective (such as, for example, a thioether linked to the therapeutic agent through an acylhydrazone linkage (see, for example, U.S. Patent No. 5,622,929). In other embodiments, the connector can be cleaved under reducing conditions (e.g., a disulfide connector). A variety of connectors are known in the art, including, for example, those that can be formed using SATA (N-succinimidyl-5-acetylthioacetate), SPDP (N- succinimidyl-3-(2-pyridyldithio)propionate), SPDB (N-succinimidyl-3-(2- pyridyldithiobutyrate) and SMPT (N-succinimidyloxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio)toluene), SPDB and SMPT. (See, for example, Thorpe et al., 1987, Cancer Res. 47:5924-5931; Wawrzynczak et al., In Immunoconjugates: Antibodies Conjugates in Radioimagery and Therapy of Cancer (CW Vogel ed., Oxford U. Press, 1987. See also U.S. Patent No. 4,880,935). In some embodiments, the linker can be cleaved by a cleaving agent, for example, an enzyme, present in the intracellular environment (e.g., in a lysosome, endosome, or caveola). The linker may be, for example, a peptide linker that can be cleaved by an intracellular peptidase or protease enzyme, including, but not limited to, a lysosomal or endosomal protease. In some embodiments, the peptide linker is at least two amino acids long or at least three amino acids long. Cleaving agents may include cathepsins B and D and plasmin, which are known to hydrolyze dipeptide drug derivatives, resulting in the release of the active drug. within target cells (see, for example, Dubowchik and Walker, 1999, Pharm. Therapeutics 83:67-123). The most typical are peptide linkers that can be cleaved by enzymes present in EGFR-expressing cells. Examples of such linkers are described, for example, in U.S. Patent No. 6,214,345, which is incorporated herein in its entirety by reference and for all purposes. In one specific embodiment, the peptide linker that can be cleaved by an intracellular protease is a Val-Cit linker or a Phe-Lys linker (see, for example, U.S. Patent No. 6,214,345, which describes the synthesis of doxorubicin with the val-cit linker). One advantage of using intracellular proteolytic release of the therapeutic agent is that the agent is typically attenuated when conjugated and the serum stabilities of the conjugates are typically high. In other embodiments, the connective is a malonate connective (Johnson et al., 1995, Anticancer Res. 15:1387-93), a maleimidobenzoyl connective (Lau et al., 1995, Bioorg-Med-Chem. 3(10):1299-1304), or a 3'-N-amide analogue (Lau et al., 1995, Bioorg-Med-Chem. 3(10): 1305-12). In still other embodiments, the connecting unit cannot be cleaved and the drug is released, for example, by degradation of the antibody. See U.S. Publication No. 20050238649, incorporated herein in its entirety by reference. An ADC comprising a non-cleaveable connector such that the ADC remains substantially outside the cell and interacts with certain receptors on a target cell surface such that binding of the ADC initiates (or prevents) a particular cell signaling pathway. In some embodiments, the connector is substantially hydrophilic (e.g., PEG4Mal and sulfo-SPDB). A hydrophilic connector can be used to reduce the extent to which the drug can be pumped out of the resistant cancer cell via MDR (multidrug-resistant) or functionally similar transporters. In other embodiments, upon cleavage, the connector functions to directly or indirectly inhibit cell growth and / or cell proliferation. For example, in some embodiments, the connector, when cleaved, can function as an intercalating agent, thereby inhibiting macromolecular biosynthesis (e.g., DNA replication, RNA transcription, and / or protein synthesis). In other embodiments, the connector is designed to facilitate collateral cell death (the death of neighboring cells) by diffusion of the connector-drug and / or the drug alone to neighboring cells. In other embodiments, the connector promotes cellular internalization. The presence of a sterically hindered disulfide bond can increase the stability of a particular disulfide bond, thereby increasing the power of the ADC. Therefore, in one embodiment, the connector includes a sterically hindered disulfide bond. A sterically hindered disulfide bond refers to a disulfide bond present in a particular molecular environment, characterized by a specific spatial arrangement or orientation of atoms, typically within the same molecule or compound, that prevents or at least partially inhibits the reduction of the disulfide bond. Thus, the presence of chemically dense (or sterically hindered) portions and / or dense amino acid side chains near the disulfide bond prevents or at least partially inhibits the disulfide bond from possible interactions that could result in the reduction of the disulfide bond. Notably, the types of connectors mentioned above are not mutually exclusive. For example, in one embodiment, the connector used in the anti-EGFR ADCs described herein is a non-cleaving connector that promotes cellular internalization. In some implementations, the ADC has the following formula (formula I): Ab-(LD)n (YO) or a pharmaceutically acceptable salt or solvate thereof; wherein Ab is the antibody, e.g., anti-EGFR antibody AbA, and (LD) is a connective-pharmacological group. The connective-pharmacological group is composed of L, which is a connective, and D, which is a pharmacological group that has, e.g., cytostatic, cytotoxic, or other therapeutic activity against a target cell, e.g., an EGFR-expressing cell; and n is an integer between 1 and 20. In some forms of realization, n ranges between 1 and 8, between 1 and 7, between 1 and 6, between 1 and 5, between 1 and 4, between 1 and 3, between 1 and 2, or is 1. In some embodiments, the -D portions are the same. In yet another embodiment, the -D portions are different. As described above, the connector can be a simple group or can include two or more components. In some embodiments, the ADC has the following formula (II): Ab-(Aa-Ww—Yy-D)n (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Ab is the antibody, for example, anti-EGFR antibody AbA, and -Aa-Ww— Yy- is a connector (L) comprising three or more components, including -A-, which is an optional elongating unit, a is 0 or 1, each —W— is independently an amino acid unit (or in some embodiments, a glucuronide unit, see also U.S. Publication No. 2012 / 0107332 A1), w is an integer ranging from 0 to 12, —Y— is a self-cleaving spacer unit, and is 0, 1 or 2; -D is a pharmacological group having, for example, cytostatic, cytotoxic, or other therapeutic activity against a target cell, for example, an EGFR-expressing cell; yn is an integer between 1 and 20. In some embodiments, a connecting component comprises an “elongating unit” (A) that links an antibody to another connecting component or to a drug group. Non-limiting examples of elongating units are shown below (where the wavy line indicates sites of covalent binding to an antibody, drug, or additional connecting components): The elongating unit (A), when present, has the capacity to link an antibody to an amino acid unit (—W—), if present, to a spacer unit (—Y—), if present; or to a drug (—D) (see Formula II). Useful functional groups that may be present in the anti-EGFR antibodies described herein, naturally or by chemical manipulation, include, but are not limited to, sulfhydryl, amino, hydroxyl, the anomeric hydroxyl group of a carbohydrate, and carboxyl. Suitable functional groups are sulfhydryl and amino. In one example, sulfhydryl groups can be generated by reduction of the intramolecular disulfide bonds of an anti-EGFR antibody. In another embodiment, sulfhydryl groups can be generated by reacting an amino group of a lysine group of an anti-EGFR antibody with 2-iminothiolane (Traut's reagent) or another sulfhydryl-generating reagent. In certain embodiments, the anti-EGFR antibody is a recombinant antibody and is designed to bear one or more lysine moieties. In other embodiments, the recombinant anti-EGFR antibody is designed to bear additional sulfhydryl groups, for example, additional cysteines. In one embodiment, the elongating unit forms a bond with a sulfur atom of the antibody. The sulfur atom may be derived from a sulfhydryl group of an antibody. Representative elongating units of this embodiment are described in the brackets of Formulas IIIa and IIIb as shown below. Illb Ww—Yy--D where L-, —W—, —Y—, -D, wey are as previously defined, and R17 is selected from —C1-C10 alkylene-, —C1-C10 alkenylene-, —C1-C10 alkynylene-, carbocyclo-, —O—(C1-C8 alkylene)-, O—(C1-C8 alkenylene)-, — O—(C1-C8 alkynylene)-, -arylene-, —C1-C10 alkylene-arylene-, —C2-C10 alkenylene-arylene, —C2-C10 alkynylene-arylene, arylene-C1-C10 alkylene-, - arylene-C2-C10 alkenylene-, -arylene-C2-C10 alkynylene-, -C1-C10 alkylene-(carbocycle)-, -C2-C10 alkenylene-(carbocycle)-, C2-C10 alkynylene-(carbocycle)-, -(carbocycle)-C1-C10 alkylene-, -(carbocycle)-C2-C10 alkenylene-, -(carbocycle)-C2-C10 alkynylene, -heterocycle-, -C1-C10 alkylene-(heterocycle)-, -C2-C10 alkenylene-(heterocycle)-, -C2-C10 alkynylene-(heterocycle)-, -(heterocycle)-C1-C10 alkylene-, -(heterocycle)-C2-C10 alkenylene-, -(heterocycle)-C1-C10 alkynylene-, —(CH2CH2O)r—, or —(CH2CH2O)r—CH2—, where r is an integer ranging from 1 to 10, wherein said alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, aryl, carbocyl, carbocycle, heterocycle, and arylene radicals, alone or as part of another group, are optionally substituted. In some embodiments, said alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, aryl, carbocyl, carbocycle, heterocycle, and arylene radicals, alone or as part of another group, are unsubstituted.In some embodiments, R17 is selected from —C1-C10 alkylene-, -carbocycle-, —O—(C1-C8 alkylene)-, -arylene-, —C1-C10 alkylene-arylene-, -arylene-C1-C10 alkylene-, —C1-C10 alkylene-(carbocycle)-, -(carbocycle)-C1-C10 alkylene-, —C3-C8 heterocycle-, —C1-C10 alkylene-(heterocycle)-, -(heterocycle)-C1-C10 alkylene-, —(CH2CH2O)r—, and —(CH2CH2O)r—CH2—; yr is an integer ranging from 1 to 10, wherein said alkylene groups are unsubstituted and the rest of the groups are optionally substituted. An illustrative elongating unit is that of Formula II where R17 is —(CH2)5— as previously described (see also US 8,309,093). Another illustrative elongating unit is that of Formula III where R17 is —(CH2CH2O)r—CH2—; and r is 2, as described above (see also US 8,309,093, which is incorporated herein by reference). Another illustrative elongating unit is that of Formula IIIa, where R17 is arylene- or C1-C10 arylene-alkylene-. In some embodiments, the aryl group is an unsubstituted phenyl group. Furthermore, another illustrative elongating unit is that of Formula IIIb, where R17 is —(CH2)5—, as previously described (see also US 8,309,093, which is incorporated into the In certain embodiments, the elongating unit is linked to the anti-EGFR antibody via a disulfide bond between a sulfur atom of the anti-EGFR antibody unit and a sulfur atom of the elongating unit. A representative elongating unit of this embodiment is described in brackets in Formula IV (see below, and see also US 8,309,093, which is incorporated herein by reference). where R17, L-, —W—, —Y—, -D, w, ey are as previously defined. 0 L---S—[—S---R17--U—]—Ww — Yy--D IV It should be noted that the S group in the formula shown below (see also US 8,309,093, which is incorporated herein by reference) refers to a sulfur atom of the antibody, unless the context otherwise indicates. L—S—-- In still other embodiments, the elongator contains a reactive site that can bond with a primary or secondary amino group of an antibody. Examples of such reactive sites include, but are not limited to, activated esters such as succinimide esters, 4-nitrophenyl esters, pentafluorophenyl esters, tetrafluorophenyl esters, anhydrides, acid chlorides, sulfonyl chlorides, isocyanates, and isothiocyanates. Representative elongator units of this embodiment are described in brackets in Formulas Va and Vb (see also US 8,309,093, which is incorporated herein by reference), where R17, L-, —W—, —Y—, -D, w, and ey are as previously defined. R17 Ww—Yy--D Va R17 Ww—Yy--D Vb In some embodiments, the elongator contains a reactive site that is reactive to a modified carbohydrate (—CHO) group that may be present on an antibody. For example, a carbohydrate may be gently oxidized using a reagent such as sodium periodate, and the resulting (—CHO) unit of the oxidized carbohydrate may be condensed with an elongator containing a functional group such as a hydrazide, an oxime, a primary or secondary amine, a hydrazine, a thiosemicarbazone, a hydrazine carboxylate, and an arylhydrazide, such as those described in Kaneko et al., 1991, Bioconjugate Chem. 2:133-41. The representative elongating units of this embodiment are shown between the brackets of Formulas Via, VIb, and VIc (see below (see also U.S. 8,309,093, which is incorporated by reference herein), where —R17-, L, —W—, —Y—, -D, wey are as previously defined. L ==N H 17 N----R17 L==N--0--R17 L ==N Ww —Yy--D Ww—Yy-D 0 0 H 17 N-----0-----R17---LL Ww — Yy--D Via VIb Vic In some embodiments, a connecting component comprises an “amino acid unit” (W). In some of these embodiments, the amino acid unit allows cleavage of the connective by a protease, thereby facilitating the release of the drug from the immunoconjugate upon exposure to intracellular proteases, such as lysosomal enzymes (Doronina et al. (2003) Nat. Biotechnol. 21:778-784). Examples of amino acid units include dipeptides, tripeptides, tetrapeptides, and pentapeptides. Examples of dipeptides include valine-citrulline (vc or val-cit), alanine-phenylalanine (af or ala-phe); phenylalanine-lysine (fk or phe-lys); phenylalanine-holysine (phe-homolys); and N-methyl-valine-citrulline (Me-val-cit). Examples of tripeptides include, but are not exhaustive, glycine-valine-citrulline (gli-val-cit) and glycine-glycine-glycine (gli-gli-gli).An amino acid unit may comprise naturally occurring amino acid residues and / or minor amino acids and / or non-naturally occurring amino acid analogues, such as citrulline. The units. Amino acids can be designed and optimized for enzymatic cleavage by a particular enzyme, e.g., a tumor-associated protease, cathepsin B, C and D, or a plasmin protease. In one embodiment, the amino acid unit W is valine-citrulline (vc or val-cit). In another aspect, the amino acid unit is phenylalanine-lysine (ie, fk). In yet another aspect of the amino acid unit, the amino acid unit is N-methylvaline-citrulline. In yet another aspect, the amino acid unit is 5-aminovaleric acid, homo phenylalanine lysine, tetraisoquinolinecarboxylate lysine, cyclohexylalanine lysine, isonepecotic acid lysine, beta-alanine lysine, glycine serine valine glutamine and isonepecotic acid. Alternatively, in some embodiments, —W— is a glucuronide unit that connects an elongating unit to a spacer unit if both the elongating and spacer units are present, connects an elongating unit to the drug group if the spacer unit is absent, and connects the linker unit to the drug if both the elongating and spacer units are absent. The glucuronide unit includes a site that can be cleaved by a P-glucuronidase enzyme (See also US 2012 / 0107332, which is incorporated herein by reference). In some embodiments, the glucuronide unit comprises a sugar portion (Su) connected via a glycosidic bond (—O'—) to a self-cleaving group (Z) of the formula shown below (See also US 2012 / 0107332, which is incorporated herein by reference). ---J—Su O'---Z—] The glycosidic bond (—O'—) is typically a cleavage site with P-glucuronidase, such as a bond that can be cleaved by P-glucuronidase In the context of a glucuronide unit, the term “self-cleaving group” refers to a di- or trifunctional chemical portion that is capable of covalently linking with two or three spaced chemical portions (i.e., the sugar portion (via a glycosidic bond), a drug group (directly or indirectly via a spacer unit), and, in some embodiments, a connector (directly or indirectly via an elongating unit)) into a stable molecule. The self-cleaving group will spontaneously cleave from the first chemical portion (e.g., the spacer unit or drug) if its bond to the sugar portion is cleaved. In some embodiments, the sugar portion (Su) is a cyclic hexose, such as a pyranose, or a cyclic pentose, such as a furanose. In some embodiments, the pyranose is a glucuronide or hexose. The sugar portion is usually in the pD conformation. In one specific embodiment, the pyranose is a pD-glucuronide portion (i.e., pD-glucuronic acid connected to the self-cleaving group —Z— via a glycosidic bond that can be cleaved by p-glucuronidase). In some embodiments, the sugar portion is unsubstituted (e.g., a naturally occurring cyclic hexose or cyclic pentose). In other embodiments, the sugar portion may be a substituted pD-glucuronide (i.e., glucuronic acid substituted with one or more groups, such as hydrogen, hydroxyl, halogen, sulfur, nitrogen or minor alkyl). In some embodiments, the glucuronide unit has one of the formulas shown below (See also US 2012 / 0107332, which is incorporated herein by reference), where Su is the sugar portion, the glycosidic bond comprises the oxygen bond between Su and the self-cleaving group Z, and each R is independently hydrogen, halo (e.g., chlorine, bromine, fluorine, etc.), —CN, —NO2, or another electron-withdrawing or electron-donating group, provided that the glucuronide unit (and Z in particular) undergoes self-cleavage upon cleavage of the glycosidic bond. In some embodiments, each R is independently hydrogen, halo (e.g., chlorine, bromine, fluorine, etc.), —CN, or —NO2. In some embodiments, the glucuronide unit has one of the formulas shown below (see also US 2012 / 0107332, which is incorporated herein by reference), where Su is the sugar portion, the glycosidic bond (—O'—) comprises the oxygen bond between Su and the self-cleaving group Z, and each R is independently hydrogen. In some embodiments, the self-cleaving group (Z) is covalently connected to the sugar portion, the drug (directly or indirectly through the spacer unit(s)), and the connector (directly or indirectly through the elongating unit(s)). In some embodiments, a drug connector conjugate has the formula shown below (See also US 2012 / 0107332, which is incorporated herein by reference). Su----O'---Z---Yy---D Aa where Su, O', Z, Y, y, D, A are already defined herein. Typically between 1 and 20 of said drug-connector conjugates may be connected to a connector. In some embodiments, an ADC comprising the glucuronide unit has one of the formulas shown below (See also US 2012 / 0107332, which is incorporated herein by reference), wherein Su, Y, y, D, A, a, and L are defined as described herein. In some embodiments, an ADC comprising the glucuronide unit has the formula shown below (See also US 2012 / 0107332, which is incorporated herein by reference), wherein Y, y, D, A, a, and L are defined herein. L In some embodiments, an ADC comprising the glucuronide unit has the formula shown below (See also US 2012 / 0107332, which is incorporated herein by reference), wherein Y, y, D and L are defined as described herein. In some embodiments, an ADC comprising the glucuronide unit has the formula shown below (See also US 2012 / 0107332, which is incorporated herein by reference), wherein Y, y, D and L are defined as described herein. In some embodiments, an ADC comprising the glucuronide unit has the formula shown below (See also US 2012 / 0107332 A1), wherein D is as described herein and mAb is a monoclonal antibody. either The spacer unit (—Y—), when present, connects an amino acid unit (or glucuronide unit; see also US 2012 / 0107332, which is incorporated herein by reference) to the drug group when an amino acid unit is present. Alternatively, the spacer unit connects the elongator unit to the drug group when the amino acid unit is absent. The spacer unit can also connect the drug unit to the antibody unit when both the amino acid unit and the elongator unit are absent. Space units are of two general types: non- Self-cleaving or self-cleaving. A non-self-cleaving spacer unit is one in which part or all of the spacer unit remains attached to the drug group after cleavage, particularly enzymatic cleavage, of an amino acid unit (or glucuronide unit) from the antibody-drug conjugate. Examples of a non-self-cleaving spacer unit include, but are not limited to, a (glycine-glycine) spacer unit and a glycine spacer unit (both shown in Scheme 1 below (see also U.S. 8,309,093, which is incorporated herein by reference)). Scheme 1 L—{-Aa—Ww--Gly—D| enzymatic cleavage v Gly----D hydrolysis V drug enzymatic cleavage Gly---Gly—D hydrolysis ♦ drug When a conjugate containing a glycine-glycine or glycine spacer unit is subjected to enzymatic cleavage by an enzyme (e.g., a tumor cell-associated protease, a cancer cell-associated protease, or a lymphocyte-associated protease), a glycine-glycine-pharmacological group or a glycine-pharmacological group is cleaved from the L-Aa-Ww-. In one embodiment, a hydrolysis reaction takes place. independent within the target cell, cleaving the glycine-drug group bond and releasing the drug. In some embodiments, a non-self-splitting spacer unit (—Y—) is -Gly-. In some embodiments, a non-self-splitting spacer unit (—Y—) is -Gly-Gly-. In one embodiment, a drug and connector conjugate is provided in which the spacer unit is absent (y=0), or a pharmaceutically acceptable salt or solvate thereof. Alternatively, a conjugate containing a self-cleaving spacer unit may allow the release of the pharmacological portion. A self-cleaving spacer unit will spontaneously separate from the second chemical portion if its bond to the first portion is cleaved. In some embodiments, —Yy— is a p-aminobenzyl alcohol (PAB) unit whose phenylene portion is substituted with Qm where Q is -C1-C8 alkyl, -C1-C8 alkenyl, -C1-C8 alkynyl, -O—(C1-C8 alkyl), -O—(C1-C8 alkenyl), -O—(C1-C8 alkynyl), -halogen, -nitro or -cyano; ym is an integer in the range between 0 and 4. The alkyl, alkenyl and alkynyl groups, either alone or as part of another group, may be optionally substituted. In some embodiments, —Y— is a PAB group that connects to —Ww— through the amino nitrogen atom of the PAB group, and is directly connected to -D through a carbonate, carbamate, or ether group. Without being limited to any particular theory or mechanism, Scheme 2 below (see also U.S. 8,309,093) shows a possible drug release mechanism from a PAB group that is directly connected to -D through a carbamate or carbonate group as described in Toki et al., 2002, J. Org. Chem. 67:1866-1872. Scheme 1 1,6-elimination drug In Scheme 2, Q is —C1-C8 alkyl, —C1-C8 alkenyl, —C1-C8 alkynyl, —O—(C1-C8 alkyl), —O—(C1-C8 alkenyl), —O—(C1-C8 alkynyl), -halogen, -nitro, or -cyano; m is an integer in the range between 0 and 4; and p is in the range between 1 and approximately 20. The alkyl, alkenyl, and alkynyl groups, either alone or as part of another group, may be optionally substituted. Other examples of self-clearing spacers include, in a non-exhaustive illustrative title, aromatic compounds that are electronically Similar to the PAB group, such as 2-aminoimidazol-5-methanol derivatives (Hay et al., 1999, Bioorg. Med. Chem. Lett. 9:2237) and ortho- or para-aminobenzylacetals. Spacers that undergo cyclization upon hydrolysis of the amide bond can be used, such as substituted and unsubstituted amides of 4-aminobutyric acid (Rodrigues et al., 1995, Chemistry Biology 2:223), appropriately substituted bicyclo[2.2.1] and bicyclo[2.2.2] ring systems (Storm et al., 1972, J. Amer. Chem. Soc. 94:5815), and amides of 2-aminophenylpropionic acid (Amsberry et al., 1990, J. Org. Chem. 55:5867). The elimination of amine-containing drugs that are substituted at the α position of glycine (Kingsbury et al., 1984, J. Med. Chem. 27:1447) are also examples of self-clearing spacers. In one respect, the spacer units (—Yy—) are represented by Formulas (X)-(XII) (see below (see also U.S. 8,309,093) where Q is —C1-C8 alkyl, —C1-C8 alkenyl, —C1-C8 alkynyl, —O—(C1-C8 alkyl), —O—(C1-C8 alkenyl), —O—(C1-C8 alkynyl), -halogen, -nitro or -cyano; ym is an integer in the range between 0 and 4. Other examples of self-clearing spacers include, by way of example, aromatic compounds that are electronically similar to the PAB group such as 2-aminoimidazol-5-methanol derivatives (see, for example, Hay et al., 1999, Bioorg. Med. Chem. Lett. 9:2237) and ortho- or para-aminobenzylacetals. Spacers that undergo cyclization upon amide bond hydrolysis can be used, such as substituted and unsubstituted amides of 4-aminobutyric acid (see, for example, Rodrigues et al., 1995, Chemistry Biology 2:223), appropriately substituted bicyclo[2.2.1] and bicyclo[2.2.2] ring systems (see, for example, Storm et al., 1972, J. Amer. Chem. Soc. 94:5815), and amides of 2-aminophenylpropionic acid (see, for example, Amsberry et al., 1990, J. Org. Chem. 55:5867). The elimination of amine-containing drugs that are substituted at the α position of glycine (see, for example, Kingsbury et al., 1984, J. Med. Chem.27:1447) is also an example of self-clearing spacers. Other suitable spacer units are disclosed in Published U.S. Patent Application No. 2005-0238649, the disclosure of which is incorporated herein by reference. Another strategy for generating ADCs involves the use of heterobifunctional crosslinkers that connect the anti-EGFR antibody to the drug portion. Examples of crosslinkers that can be used include N-succinimidyl 4-(5-nitro-2-pyridyldithio)-pentanoate or the highly water-soluble analog N-sulfosuccinimidyl 4-(5-nitro-2-pyridyldithio)-pentanoate, N-succinimidyl-4-(2-pyridyldithio)butyrate (SPDB), N-succinimidyl-4-(5-nitro-2-pyridyldithio)butyrate (SNPB), and N-sulfosuccinimidyl-4-(5-nitro-2-pyridyldithio)butyrate (SSNPB), N-succinimidyl-4-methyl-4-(5-nitro-2-pyridyldithio)pentanoate (SMNP), N-succinimidyl-4-(5-N,N-dimethylcarboxamido-2-pyridyldithio) butyrate (SCPB) or N-sulfosuccinimidyl 4-(5-N,N-dimethylcarboxamido-2-pyridyldithio) butyrate (SSCPB)). The antibodies of the invention can be modified with the crosslinkers N-succinimidyl 4-(5-nitro-2-pyridyldithio)-pentanoate, N- Sulfosuccinimidyl 4-(5-nitro-2-pyridyldithio)-pentanoate, SPDB, SNPB, SSNPB, SMNP, SCPB, or SSCPB, can then react with a small excess of a particular drug containing a thiol portion to give excellent yields of an ADC. Preferably, the crosslinkers are compounds of formula as shown below (see also U.S. Patent No. 6,913,748, which is incorporated herein by reference). where R, R1, R2 and R3 are the same or different and are H, methyl, ethyl, or linear, branched, or occyclic alkyl having between 3 and 6 carbon atoms, n is 0 or an integer between 1 and 4, X and Y are the same or different and are H, CONR4R5 or NO2, with the condition that X and Y are not both H at the same time, R4 and R5 are the same or different and are each H, methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, iso-butyl or tert-butyl, and Z is SO3-M+ or H, wherein M+ represents a metal ion or a tetraalkylammonium ion, with the condition that when X and / or Y is NO2, Z is not H. Other heterobifunctional crosslinkers and methods for making ADCs using the same are described in U.S. Patent No. 6,913,748, which is expressly incorporated by reference herein. In one embodiment, charged connectors (also referred to as pro-charged connectors) are used to conjugate anti-EGFR antibodies to drugs to form ADCs. Charged connectors include connectors that become charged after cellular processing.The presence of one or more charged groups in the connector of a particular ADC or in the drug after cell processing provides several advantages, such as (i) increased water solubility of the ADC, (ii) the ability to operate at higher concentrations in aqueous solutions, (iii) the ability to bind a large number of drug molecules per antibody, potentially resulting in greater potency, (iv) the potential for charged conjugate species to be retained within the target cell, resulting in greater potency, and (v) improved sensitivity of multidrug-resistant cells, which would otherwise be unable to export charged drug species from the cell. Examples of some suitable charged or procharged ADCs and their synthesis are shown in Figures 1 through 10 of U.S. Patent No. 8,236,319 and are incorporated herein by reference.Preferably, charged or procharged crosslinkers are those containing sulfonate, phosphate, carboxyl or quaternary amine substituents that significantly increase the solubility of ADCs, especially for ADCs. with between 2 and 20 conjugated drugs. Conjugates prepared from connectors containing a procharged portion would produce one or more charged portions after the conjugate is metabolized in a cell. In a further embodiment, the ADC of the invention comprises a connector having the form shown below (see also U.S. Patent No. 8,236,319, which is incorporated herein by reference), R9 R10 R5 R6 R-| R2 where Y' represents a functional group that allows reaction with an antibody; Q represents a functional group that allows connection of a drug through a disulfide, thioether, thioester, peptide, hydrazone, ester, ether, carbamate or amide bond;R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are the same or different and are H, linear alkyl having between 1 and 6 carbon atoms, branched or cyclic alkyl having between 3 and 6 carbon atoms, linear, alkenyl or alkynyl branched or cyclic having between 2 and 6 carbon atoms, anions, such as, but not limited to, SO3-, X—SO3-, OPO32-, X— OPO32-, PO32-, X—PO32-, CO2—, cations, such as, but not limited to, a nitrogen-containing heterocycle, N+R11R12R13, or X—N+R11R12R13 or a phenyl, wherein: R11, R12, and R13 are the same or different and are H, linear alkyl having between 1 and 6 carbon atoms, or branched or cyclic alkyl having between 3 and 6 carbon atoms and X represents phenyl or a linear alkyl having between 1 and 6 carbon atoms, or a branched or cyclic alkyl having between 3 and 6 carbon atoms; l, m, yn are 0 or an integer between 1 and 4;A is a phenyl or substituted phenyl, wherein the substituent is a linear alkyl that; has between 1 and 6 carbon atoms, or a branched oc^cyclic alkyl having between 3 and 6 carbon atoms, or a charged substituent chosen from anions, such as, but not limited to, SO3-, X—SO3-, OPO32-, X— OPO32-, PO32-, X—PO32-, CO2—, and cations, such as, but not limited to, a nitrogen-containing heterocycle, N+RiiRi2Ri3 or X—N+RiiRi2Ri3, wherein X has the same definition as previously given, and wherein g is 0 or i; Z is an optional polyethyleneoxyl unit of formula (OCH2CH2)p, where p is 0 or an integer between 2 and approximately 1000, or a Fi-Ei-P-E2-F2 unit in which Ei and E2 are the same or different and are C=O, O, or NRi4, where Ri4 is H, a linear alkyl having between 1 and 6 carbon atoms, an oc-cyclic branched alkyl having between 3 and 6 carbon atoms, a linear, oc-cyclic branched alkenyl or alkynyl having between 2 and 6 carbon atoms;P is a peptide unit of between 2 and 20 amino acids in length, wherein Ei or E2 can be connected to the peptide via the terminal nitrogen, terminal carbon or via a side chain of one of the amino acids of the peptide; and Fi and F2 are the same or different and are an optional polyethyleneoxyl unit of formula (OCH2CH2)p, wherein p is 0 or an integer between 2 and approximately 1000, with the condition that when Z is not Fi-Ei-P-E2-F2, at least one of Ri, R2, R3, R4, R5, R6, R7, R8, R9, and Ri0 is a charged substituent or when g is i, at least one of A, Ri, R2, R3, R4, R5, R6, R7, R8, R9, and Ri0 is a charged substituent. Other examples of connectives that can be used with the compositions and methods include valine-citrulline; maleimidocaproyl; aminobenzoic acids; p-aminobenzylcarbamoyl (PAB); connectives that can be cleaved by lysosomal enzymes; maleimidocaproyl-polyethylene glycol (MC(PEG)6-OH); N-methyl-valine citrulline; N-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC); N-Succinimidil 4-(2-pyridyldithio)butanoate (SPDB); and N-Succinimidil 4-(2-pyridylthio)pentanoate (SPP) (See also U.S. Patent 2011 / 0076232). Another connector for use in the invention includes an avidin-biotin link to provide an avidin-biotin-containing ADC (See also U.S. Patent No. 4,676,980, PCT Publications Nos. WO1992 / 022332A2, WO1994 / 016729A1, WO1995 / 015770A1, WO1997 / 031655A2, WO1998 / 035704A1, WO1999 / 019500A1, WO2001 / 09785A2, WO2001 / 090198A1, WO2003 / 093793A2, WO2004 / 050016A2, WO2005 / 081898A2, WO2006 / 083562A2, WO2006 / 089668A1, WO2007 / 150020A1, WO2008 / 135237A1, WO2010 / 111198A1, WO2011 / 057216A1, WO2011 / 058321A1, WO2012 / 027494A1, and EP77671B1), wherein some of said connectors are resistant to biotinidase cleavage. Additional connectors that may be used in the invention include the cohesin / dockerin pair to provide an ADC containing cohesiona-dockerin (See U.S. Publications Nos. WO2008 / 097866A2, WO2008 / 097870A2, WO2008 / 103947A2, and WO2008 / 103953A2). Additional connectors for use in the invention may contain non-peptide polymers (examples include, but are not limited to, polyethylene glycol, polypropylene glycol, polyethoxylated polyols, polyvinyl alcohol, polysaccharides, dextran, polyvinyl ethyl ether, PLA (poly(lactic acid)), PLGA (poly(lactic acid-glycolic acid)), and combinations thereof, wherein a preferred polymer is polyethylene glycol) (See also PCT Publication No. WO2011 / 000370). Additional connectors are also described in WO 2004-010957, U.S. Publication No. 20060074008, and the Publication of the U.S. Publication No. 20050238649, and U.S. Publication No. 20060024317, each of which is incorporated herein by reference in its entirety). For an ADC comprising a maytansinoid, many positions of the maytansinoids can serve as a position for chemical connection to the connecting portion. In one embodiment, the maytansinoids comprising a connecting portion containing a reactive chemical group are C-3 esters of maytansinol and their analogues, wherein the connecting portion contains a disulfide bond and the reactive chemical group comprises an N-succinimidyl or N-sulfosuccinimidyl ester. For example, the C-3 position bearing a hydroxyl group, the C-14 position modified with hydroxymethyl, the C-15 position modified with hydroxyl, and the C-20 position bearing a hydroxyl group are all useful. The connecting portion is most preferentially connected to the C-3 position of maytansinol. The conjugation of a drug to an antibody via a linker can be carried out using any technique known to the art. Several different reactions are available for the covalent linkage of drugs and linkers to antibodies. This can be accomplished by reacting the amino acid residues of the antibody, including the amine groups of lysine, the free carboxylic acid groups of glutamic and aspartic acids, the sulfhydryl groups of cysteine, and the various portions of aromatic amino acids. One of the most commonly used nonspecific methods of covalent linkage is the carbodiimide reaction to connect a carboxyl (or amino) group of a compound to the amino (or carboxyl) groups of the antibody. In addition, bifunctional agents such as dialdehydes or imidoesters have been used for Connecting the amino group of a compound to the amino groups of an antibody is one method. The Schiff base reaction is also available for binding drugs to antibodies. This method involves the oxidation of a drug containing glycol or hydroxyl groups with periodate, forming an aldehyde that is then reacted with the binding agent. The binding occurs through the formation of a Schiff base with the amino groups of the antibody. Isothiocyanates can also be used as coupling agents for the covalent binding of drugs to antibodies. Persons skilled in the art are aware of other techniques, and these are within the scope of the invention. In certain embodiments, an intermediate, which is the precursor of the connector, is reacted with the drug under appropriate conditions. In certain embodiments, reactive groups of the drug or the intermediate are used. The reaction product between the drug and the intermediate, or the derivatized drug, is subsequently reacted with the anti-EGFR antibody under appropriate conditions. The synthesis and structure of examples of connectors, elongating units, amino acid units, and self-clearing spacer units are described in U.S. Patent Application Publications Nos. 20030083263, 20050238649, and 20050009751, each of which is incorporated herein by reference. The stability of the ADC can be measured using standard analytical techniques such as mass spectrometry, HPLC, and the LC / MS separation / analysis technique. IV. Purification of anti-EGFR ADCs Antibody-to-drug (ADC) purification can be achieved by collecting ADCs with specific drug-to-antibody ratios (DARs). For example, hydrophobic resin can be used to separate drug-laden ADCs from those with optimal DARs, such as a DAR of 4 or less. In one embodiment, a hydrophobic resin is added to an ADC mixture so that unwanted ADCs, i.e., drug-laden ADCs, bind to the resin and can be selectively removed from the mixture. In certain embodiments, the separation of the ADCs can be carried out by contacting a mixture of ADCs (for example, a mixture comprising a drug-loaded ADC species of 4 or less and a drug-loaded ADC species of 6 or more) with a hydrophobic resin, wherein the amount of resin is sufficient to allow the binding of the drug-loaded species being removed from the ADC mixture.The resin and ADC mixture are worked together so that the ADC species being removed (e.g., a species with a drug loading of 6 or more) binds to the resin and can be separated from the other ADC species in the mixture. The amount of resin used in the method is based on the weight ratio between the species to be removed and the resin, where the amount of resin used does not allow for significant binding of the desired drug-loading species. Consequently, methods can be used to reduce the average DAR from 5.5 to less than 4. Furthermore, the purification methods described herein can be used to isolate ADCs with any desired drug-loading species range, for example, a species with a drug loading of 4 or less. species with a drug load of 3 or less, a species with a drug load of 2 or less, a species with a drug load of 1 or less. Certain molecule species bind to a surface based on hydrophobic interactions between the species and a hydrophobic resin. In one embodiment, the method of the invention relates to a purification process based on the intermixture of a hydrophobic resin and a mixture of anti-drug compounds (ADCs), where the amount of resin added to the mixture determines which species (e.g., ADCs with a DAR of 6 or more) will bind. After the production and purification of an antibody from an expression system (e.g., a mammalian expression system), the antibody is reduced and coupled to a drug via a conjugation reaction. The resulting ADC mixture frequently contains ADCs that have a DAR range, for example, between 1 and 8. In one embodiment, the ADC mixture comprises a species with a drug load of 4 or less and a species with a drug load of 6 or more.According to the methods of the invention, the mixture of ADCs can be purified using a process, such as, but not limited to, a batch process, whereby ADCs having a drug-loaded species of 4 or less are selected and separated from ADCs having a higher drug load (e.g., ADCs having a drug-loaded species of 6 or more). Notably, the purification methods described herein can be used to isolate ADCs having any desired DAR range, e.g., a DAR of 4 or less, a DAR of 3 or less, or a DAR of 2 or less. Accordingly, in one embodiment, an ADC mixture comprising a species with a drug loading of 4 or less and a species with Drug-laden species of 6 or more may be contacted with a hydrophobic resin to form a resin mixture, wherein the amount of hydrophobic resin that is contacted with the ADC mixture is sufficient to allow binding of the drug-laden species of 6 or more to the resin, but does not allow significant binding of the drug-laden species of 4 or less; and removing the hydrophobic resin from the ADC mixture, so as to obtain the composition comprising the ADCs, wherein the composition comprises less than 15% of the drug-laden species of 6 or more, and wherein the ADC comprises an antibody conjugated to an aurstatin.In a separate embodiment, the method of the invention comprises contacting an ADC mixture comprising a drug-loaded species of 4 or less and a drug-loaded species of 6 or more with a hydrophobic resin to form a resin mixture, wherein the amount of hydrophobic resin that contacts the ADC mixture is sufficient to allow binding of the drug-loaded species of 6 or more to the resin, but does not allow significant binding of the drug-loaded species of 4 or less; and removing the hydrophobic resin from the ADC mixture, so as to obtain the composition comprising the ADCs, wherein the composition comprises less than 15% of the drug-loaded species of 6 or more, and wherein the ADC comprises an antibody conjugated to an aurstatin, wherein the weight of hydrophobic resin is between 3 and 12 times the weight of the drug-loaded species of 6 or more in the ADC mixture. The ADC separation method described herein can be carried out using a batch purification method. The batch purification process generally involves adding the ADC mixture to the resin. The hydrophobic resin is placed in a container, mixed, and subsequently separated from the supernatant. For example, in the context of batch purification, a hydrophobic resin can be prepared in, or equilibrated with, the desired buffer solution. A slurry of the hydrophobic resin can then be obtained. The ADC mixture can then be contacted with the slurry to adsorb the specific ADC species to be separated by the hydrophobic resin. The solution comprising the desired ADCs that do not bind to the hydrophobic resin material can then be separated from the slurry, for example, by filtration or by allowing the slurry to settle and removing the supernatant. The resulting slurry can be subjected to one or more washing steps. To elute the bound ADCs, the salt concentration can be reduced. In one embodiment, the process used in the invention includes no more than 50 g of hydrophobic resin. Accordingly, a batch method can be used to contact an ADC mixture comprising a species with a drug load of 4 or less and a species with a drug load of 6 or more with a hydrophobic resin to form a resin mixture, wherein the amount of hydrophobic resin contacted with the ADC mixture is sufficient to allow binding of the species with a drug load of 6 or more to the resin, but does not allow significant binding of the species with a drug load of 4 or less; and removing the hydrophobic resin from the ADC mixture, so as to obtain the composition comprising the ADCs, wherein the composition comprises less than 15% of the species with a drug load of 6 or more, and wherein the ADC comprises an antibody conjugated to an aurstatin. In a separate embodiment, a batch method is used to contact A mixture of ADCs comprising a species with a drug load of 4 or less and a species with a drug load of 6 or more with a hydrophobic resin to form a resin mixture, wherein the amount of hydrophobic resin that comes into contact with the ADC mixture is sufficient to allow binding of the species with a drug load of 6 or more to the resin, but does not allow significant binding of the species with a drug load of 4 or less; and removing the hydrophobic resin from the ADC mixture, so as to obtain the composition comprising the ADCs, wherein the composition comprises less than 15% of the species with a drug load of 6 or more, and wherein the ADC comprises an antibody conjugated to an aurstatin, wherein the weight of hydrophobic resin is between 3 and 12 times the weight of the species with a drug load of 6 or more in the ADC mixture. Alternatively, in a separate embodiment, purification can be carried out using a circulation process, whereby the resin is packed in a vessel and the ADC mixture is passed over the hydrophobic resin bed until the specific ADC species to be separated have been removed. The supernatant (containing the desired ADC species) is then pumped from the vessel and the resin bed can be subjected to washing steps. A circulation process can be used to contact an ADC mixture comprising a drug-loaded species of 4 or less and a drug-loaded species of 6 or more with a hydrophobic resin to form a resin mixture, wherein the amount of hydrophobic resin that is contacted with the ADC mixture is sufficient to allow the binding of the drug-loaded species of 6 or more to the resin, but does not allow a binding significant of the species with a drug load of 4 or less; and removing the hydrophobic resin from the ADC mixture, so as to obtain the composition comprising the ADCs, wherein the composition comprises less than 15% of the species with a drug load of 6 or more, and wherein the ADC comprises an antibody conjugated to an aurstatin.In a separate embodiment, a circulation process is used to contact an ADC mixture comprising a drug-loaded species of 4 or less and a drug-loaded species of 6 or more with a hydrophobic resin to form a resin mixture, wherein the amount of hydrophobic resin that contacts the ADC mixture is sufficient to allow binding of the drug-loaded species of 6 or more to the resin, but does not allow significant binding of the drug-loaded species of 4 or less; and removing the hydrophobic resin from the ADC mixture, so as to obtain the composition comprising the ADCs, wherein the composition comprises less than 15% of the drug-loaded species of 6 or more, and wherein the ADC comprises an antibody conjugated to an aurstatin, wherein the weight of hydrophobic resin is between 3 and 12 times the weight of the drug-loaded species of 6 or more in the ADC mixture. Alternatively, a continuous flow process can be used to purify an ADC mixture to obtain a composition comprising a majority of ADCs with a certain desired DAR. In a continuous flow process, the resin is packed in a vessel, for example, a column, and the ADC mixture is passed through the packed resin such that the desired ADC species does not substantially bind to the resin and flows through it, while the unwanted ADC species binds to the resin. A process of Continuous flow can be carried out in single-pass mode (where the ADC species of interest are obtained as a result of a single pass through the vessel resin) or in multi-pass mode (where the ADC species of interest are obtained as a result of multiple passes through the vessel resin). The continuous flow process is carried out such that the selected weight of resin binds to the unwanted ADC population, and the desired ADCs (e.g., DARs between 2 and 4) flow through the resin and are collected in the continuous flow after one or more passes. A continuous flow process can be used to contact an ADC mixture comprising a drug-loaded species of 4 or less and a drug-loaded species of 6 or more with a hydrophobic resin, wherein the amount of hydrophobic resin that is contacted with the ADC mixture is sufficient to allow binding of the drug-loaded species of 6 or more to the resin, but does not allow significant binding of the drug-loaded species of 4 or less, wherein the drug-loaded species of 4 or less passes through the resin and is subsequently collected after one or more steps, so as to obtain the composition comprising the desired ADCs (e.g., DAR between 2 and 4), wherein the composition comprises less than 15% of the drug-loaded species of 6 or more, and wherein the ADC comprises an antibody conjugated to an aurstatin.In a separate embodiment, a continuous flow process is used to contact an ADC mixture comprising a species with a drug load of 4 or less and a species with a drug load of 6 or more with a hydrophobic resin by passing the ADC mixture through a resin, wherein the amount of hydrophobic resin being put into contact with the ADC mixture is sufficient to allow binding of the drug-loaded species of 6 or more to the resin, but does not allow significant binding of the drug-loaded species of 4 or less, wherein the drug-loaded species of 4 or less passes through the resin and is subsequently collected, so as to obtain the composition comprising the ADCs, wherein the composition comprises less than 15% of the drug-loaded species of 6 or more, and wherein the ADC comprises an antibody conjugated to an aurstatin, wherein the amount by weight of hydrophobic resin is between 3 and 12 times the weight of the drug-loaded species of 6 or more in the ADC mixture. After a continuous flow process, the resin can be washed with one or more consecutive washes to recover additional ADCs with the desired DAR range (found in the wash filtrate). For example, multiple washes with lower conductivity can be used to recover additional ADCs with the desired DAR. The eluent material obtained from washing the resin can then be combined with the filtrate from the continuous flow process for improved recovery of the ADCs with the desired DAR. The aforementioned purification methods—batch, circulation, and continuous flow—rely on the use of a hydrophobic resin to separate high- and low-dose drug-loaded ADC species. The hydrophobic resin comprises hydrophobic groups that interact with the hydrophobic properties of the ADCs. The hydrophobic groups of the ADCs interact with the hydrophobic groups within the hydrophobic resin. The more hydrophobic a protein is, the stronger it will interact with the hydrophobic resin. Hydrophobic resins typically comprise a base matrix (e.g., cross-linked agarose or synthetic copolymer material) to which hydrophobic ligands (e.g., alkyl or aryl groups) are attached. Many commercially available hydrophobic resins exist. Examples include, but are not limited to, Phenyl Sepharose™ 6 Fast Flow with low or high substitution (Pharmacia LKB Biotechnology, AB, Sweden); Phenyl Sepharose™ High Performance (Pharmacia LKB Biotechnology, AB, Sweden); Octyl Sepharose™ High Performance (Pharmacia LKB Biotechnology, AB, Sweden); Fractogel™ EMD Propyl or Fractogel™ EMD Phenyl columns (E. Merck, Germany); Macro-Prep™ Methyl or Macro-Prep™ t-Butyl Supports (Bio-Rad, California); and WP HI-Propil (C3)™ (JT Baker, New Jersey). and ToyopearlTM ether, hexyl, phenyl or butyl (TosoHaas, PA). In one embodiment, the hydrophobic resin is a butyl hydrophobic resin.In another embodiment, the hydrophobic resin is a phenyl hydrophobic resin. In another embodiment, the hydrophobic resin is a hexyl hydrophobic resin, an octyl hydrophobic resin, or a decyl hydrophobic resin. In one embodiment, the hydrophobic resin is a methalene polymer having n-butyl ligands (e.g., TOYOPEARL® Butyl-600M). Other methods for purifying ADC mixtures to obtain a composition having a desired DAR are described in U.S. Application No. 14 / 210,602 (U.S. Patent Application Publication No. US 2014 / 0286968), which is incorporated herein by reference in its entirety. V. Uses of anti-EGFR antibodies and anti-EGFR ADCs The antibodies and antibody portions (and ADCs) of the invention are preferably capable of inhibiting human EGFR activity both in vivo and in vitro. Accordingly, such antibodies and antibody portions of the invention can be used to inhibit hEGFR activity, for example, in a cell culture containing hEGFR, in human subjects, or in other mammalian subjects that have EGFR with which an antibody of the invention cross-reacts. In one embodiment, the invention provides a method for inhibiting hEGFR activity comprising contacting hEGFR with an antibody or antibody portion of the invention in such a way as to inhibit hEGFR activity. For example, in a cell culture that contains, or is suspected of containing, hEGFR, an antibody or antibody portion of the invention can be added to the culture medium to inhibit hEGFR activity in the culture. In another embodiment, the invention provides a method for reducing hEGFR activity in a subject, advantageously in a subject suffering from a disease or disorder in which EGFR activity is detrimental. The invention provides methods for reducing EGFR activity in a subject suffering from such a disease or disorder, wherein it comprises administering to the subject an antibody or antibody portion of the invention in such a way as to reduce EGFR activity in the subject. Preferably, the EGFR is human EGFR, and the subject is a human subject. Alternatively, the subject may be a mammal expressing an EGFR to which the antibodies of the invention are capable of binding. Furthermore, the subject may be a mammal into which EGFR has been introduced (for example, by EGFR administration or by expression). (of a transgene for EGFR). The antibodies of the invention can be administered to a human subject for therapeutic purposes. Furthermore, the antibodies of the invention can be administered to a non-human mammal that expresses an EGFR to which the antibody is capable of binding for veterinary purposes or as an animal model of human disease. In this latter case, such animal models can be useful for evaluating the therapeutic efficacy of the antibodies of the invention (for example, by evaluating dosages and the progression of administration over time). As used in this documentation, the term “a disorder in which EGFR activity is detrimental” includes diseases and other disorders where the presence of EGFR in an individual with the disorder has been shown or is suspected to be responsible for the pathophysiology of the disorder or is a contributing factor to its worsening. Accordingly, a disorder in which EGFR activity is detrimental is a disorder in which a reduction in EGFR activity is expected to alleviate the symptoms and / or progression of the disorder. Such disorders may be evidenced, for example, by an increased concentration of EGFR in a biological fluid from an individual with the disorder (e.g., an increased concentration of EGFR in a tumor, serum, plasma, synovial fluid, etc. of the individual), which can be detected, for example, using an anti-EGFR antibody as previously described.Non-limiting examples of disorders that can be treated with the antibodies of the invention, for example, AbA, or antigen-binding fragments thereof, include those disorders discussed below. For example, suitable disorders include, by way of example (not exhaustive), a variety of cancer types, including a, a. The list of cancers that may be treated using the compositions and methods disclosed herein includes, but is not limited to, breast cancer, lung cancer, glioma, prostate cancer, pancreatic cancer, colon cancer, head and neck cancer, and kidney cancer. Other examples of cancers that may be treated using the compositions and methods disclosed herein include squamous cell carcinoma (e.g., squamous cell lung cancer or squamous cell head and neck cancer), triple-negative breast cancer, non-small cell lung cancer, colorectal cancer, and mesothelioma. In one embodiment, the antibodies and ADCs disclosed herein are used to treat a solid tumor, for example, by inhibiting the growth or reducing the size of a solid tumor that overexpresses EGFR or is EGFR-positive. In one embodiment, the invention is directed to the treatment of EGFR-amplified squamous cell lung cancer. In another embodiment, the antibodies and ADCs disclosed herein are used to treat EGFR-amplified squamous cell head and neck cancer. In yet another embodiment, the antibodies and ADCs disclosed herein are used to treat triple-negative breast cancer (TNBC). The diseases and disorders described herein may be treated with anti-EGFR antibodies or ADCs of the invention, as well as pharmaceutical compositions comprising such anti-EGFR antibodies or ADCs. In certain embodiments, the antibodies and ADCs disclosed herein are administered to a subject in need for the purpose of treating advanced solid tumors likely to exhibit elevated levels of epidermal growth factor receptor (EGFR). Examples of such tumors include, but are not limited to, cell carcinoma. squamous cell carcinoma of the head and neck, non-small cell lung cancer, triple-negative breast cancer, colorectal carcinoma, and glioblastoma multiforme. In certain embodiments, the invention includes a method for inhibiting or reducing solid tumor growth in a subject having a solid tumor, wherein said method comprises administering an anti-EGFR antibody or ADC described herein to the subject having the solid tumor, thereby inhibiting or reducing solid tumor growth. In certain embodiments, the solid tumor is a non-small cell lung carcinoma or a glioblastoma. In further embodiments, the solid tumor is an EGFRvIII-positive tumor or an EGFR-expressing solid tumor. In further embodiments, the solid tumor is an EGFR-amplified solid tumor or an EGFR-overexpressing solid tumor. In certain embodiments, the anti-EGFR antibodies or ADCs described herein are administered to a subject having glioblastoma multiforme, alone or in combination with an additional agent, for example, radiation and / or temozolomide. In certain embodiments, the invention includes a method for inhibiting or reducing solid tumor growth in a subject having a solid tumor identified as an EGFR-expressing or EGFR-overexpressing tumor (or an EGFRvIII-expressing tumor), wherein said method comprises administering an anti-EGFR antibody or anti-ADC described herein to the subject having the solid tumor, such that solid tumor growth is inhibited or reduced. Methods for identifying EGFR-expressing tumors (e.g., EGFR-overexpressing tumors) are known in the art and include FDA-approved validation tests and assays. For example, the EGFR pharmDx™ assay (Dako North America, Inc.) is a system of A qualitative immunohistochemical (IHC) component used to identify EGFR expression in normal and neoplastic tissues routinely fixed for histological evaluation. EGFR pharmDx specifically detects the EGFR protein (HER1) in EGFR-expressing cells. In addition, PCR-based assays can also be used to identify tumors that overexpress EGFR. For example, these assays can use primers that are specific for the EGFR variant gene (e.g., SEQ ID NO: 33) and / or cDNA, resulting in the amplification of the EGFR gene / cDNA, or a portion thereof. The subsequently amplified PCR products can be analyzed, for example, by gel electrophoresis using standard methods known in the art to determine the size of the PCR products. Such tests can be used to identify tumors that can be treated with the methods and compositions described herein. Any of the gene therapy methods available in the art may be used in accordance with the present invention. For general reviews of gene therapy methods, see Goldspiel et al., 1993, Clinical Pharmacy 12:488-505; Wu and Wu, 1991, Biotherapy 3:87-95; Tolstoshev, 1993, Ann. Rev. Pharmacol. Toxicol. 32:573-596; Mulligan, Science 260:926-932 (1993); and Morgan and Anderson, 1993, Ann. Rev. Biochem. 62:191-217; May 1993, TIBTECH 11(5):155-215. Commonly known methods in the art of recombinant DNA technology that may be used are described in Ausubel et al. (editors), Current Protocols in Molecular Biology, John Wiley & Sons, New York (1993); and Kriegler, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, New York (1990). A detailed description of Various methods of gene therapy are provided in US20050042664 A1 which is incorporated herein by reference. In another aspect, this application presents a method for treating (e.g., curing, suppressing, alleviating, delaying, or preventing the onset, or preventing the recurrence or relapse) or preventing an EGFR-associated disorder in a subject. The method includes administering to the subject an EGFR-binding agent (in particular, an antagonist), e.g., an anti-EGFR antibody or fragment thereof as described herein, in a quantity sufficient to treat or prevent the EGFR-associated disorder. The EGFR antagonist, e.g., the anti-EGFR antibody or fragment thereof, may be administered to the subject alone or in combination with other therapeutic modalities as described herein. The antibodies or ADCs of the invention, or the antigen-binding portions thereof, may be used alone or in combination to treat such diseases. It is understood that the antibodies of the invention, or their antigen-binding portions, may be used alone or in combination with an additional agent, for example, a therapeutic agent, wherein such additional agent is selected by persons skilled in the art according to the desired purpose. For example, the additional agent may be a therapeutic agent recognized in the art as useful for treating the disease or condition being treated by the antibody of the present invention. The additional agent may also be an agent that imparts a beneficial attribute to the therapeutic composition, for example, an agent that affects the viscosity of the composition. It should also be understood that the combinations to be included in the present invention are those combinations useful for the intended purpose. The agents listed below are given for illustrative purposes and are not intended to be exhaustive. The combinations that are part of this invention may be the antibodies of the present invention and at least one additional agent selected from the lists presented below. The combination may also include more than one additional agent, for example, two or three additional agents, if the combination is such that the resulting composition can perform its intended function. Combination therapy may include one or more EGFR antagonists, e.g., anti-EGFR antibodies or fragments thereof, formulated with, and / or co-administered with, one or more additional therapeutic agents, e.g., one or more cytokines and growth factor inhibitors, immunosuppressive agents, anti-inflammatory agents (e.g., systemic anti-inflammatory agents), antifibrotic agents, metabolic inhibitors, enzyme inhibitors, and / or cytotoxic or cytostatic agents, mitotic inhibitors, antitumor antibiotics, immunomodulatory agents, vectors for gene therapy, alkylating agents, antiangiogenic agents, antimetabolites, boron-containing agents, chemoprotective agents, hormones, antihormonal agents, corticosteroids, photoactive therapeutic agents, oligonucleotides, radionuclide agents, topoisomerase inhibitors, tyrosine kinase inhibitors, or radiosensitizers, as described in more detail herein.In one particular embodiment, the anti-EGFR binding proteins described herein, for example, anti-EGFR antibodies, are used in combination with an anticancer or antineoplastic agent. The terms “anticancer agent” and “antineoplastic agent” refer to drugs used to treat malignancies, such as cancerous growths. Drug therapy may be used alone or in combination with other treatments, such as surgery or radiation therapy. Several classes of drugs may be used in cancer treatment, depending on the nature of the organ involved. For example, breast cancer is commonly stimulated by estrogens and may be treated with drugs that inactivate sex hormones. Similarly, prostate cancer may be treated with drugs that inactivate androgens, the male sex hormone.The anticancer agents that can be used in conjunction with the anti-EGFR antibodies or ADCs of the invention include, among others, the following agents: Agent Anti- Cancerous Comments Examples Antibodies (a) antibodies other than anti-EGFR antibodies; and (b) anti-EGFR antibodies that bind to epitopes different Antibodies that are bind to IGF-1R (insulin-like growth factor receptor 1), which is expressed on the cell surface of most of human cancers Antibodies that are bind to EGFR (epidermal growth factor receptor); Mutations that affect EGFR expression or activity may result in cancer A12 (mAb completely) humanized) 19D12 (mAb completely humanized) Cp751-871 (mAb fully humanized) H7C10 (humanized mAb) alfaIR3 (mouse) ScFV / FC (chimera mouse / human) EM / 164 (mouse) Matuzumab (EMD72000) Erbitux® / Cetuximab (Imclone) Vectibix® / Panitumumab (Amgen) mAb 806 Nimotuxumab (TheraCIM) AVEO (AV299) (AVEO) AMG102 (Amgen) 5D5 (OA-5d5) (Genentech) Antibodies that are They bind to cMET (Mesenchymal-epithelial transition factor); a member of the MET family of tyrosine receptors kinases) Anti-ErbB3 antibodies that bind to different epitopes H244G11 (Pierre Fabre) Ab #14 (MM 121-14) Herceptin® (Trastuzumab; Genentech) 1B4C3; 2D1D12 (U3 Pharma AG) Molecules Small ones aimed at IGF1R Insulin-like growth factor receptor type 1 that is expressed on the cell surface of many types of human cancer NVP-AEW541-A BMS-536,924 (1H- benzoimidazole-2-yl)-1H-pyridin-2- one) BMS-554,417 Cycloligan TAE226 PQ401 Small Molecules directed to EGFR EGFR (receptor of epidermal growth factor); Iressa® / Gefitinib (AstraZeneca) CI-1033 (PD 183805) (Pfizer) Lapatinib (GW-572016) (GlaxoSmithKline) Overexpression or mutations that affect expression or EGFR activity may result in cancer Tykerb® / Lapatinib Ditosylate (Smith Kline Beecham) Tarceva ® / Erlotinib HCL (OSI- 774) (OSI Pharma) PKI-166 (Novartis) PD-158780 EKB-569 Tyrphostin AG 1478 (4-(3- Chloroanillino)-6,7-dimethoxyquinazoline) Molecules Small ones that are direct to cMET cMET (factor of mesenchymoepithelial transition); a member of the MET family of tyrosine kinase receptors) PHA665752 ARQ 197 Antimetabolites Fluorouracil (5-FU) Capecitabine / XELODA® (HLR Roche) 5-Trifluoromethyl-2'-deoxyuridine Methotrexate sodium (Trexall) (Barr) Raltitrexed / Tomudex® (AstraZeneca) Pemetrexed / Alimta® (Lilly) Tegafur Cytosine Arabinoside (Cytarabine, Ara-C) / Thioguanine® (GlaxoSmithKline) 5-azacytidine 6-mercaptopurine (Mercaptopurine, 6-MP) Azathioprine / Azasan® (AAIPHARMA LLC) 6-thioguanine (6-TG) / Purinethol® (TEVA) Pentostatin / Nipent® (Hospira Inc.) Fludarabine phosphate / Fludara® (Bayer Health Care) Cladribine (2-CdA, 2- chlorodeoxyadenosine) / Leustatin® (Ortho Biotech) Allocation agents An antineoplastic alkylating agent is an alkylating agent that Ribonucleotide inhibitor reductase (RNR) Cyclophosphamide / Cytoxan (BMS) joins an alkyl group to Neosar (TEVA) DNA. Because the Ifosfamide / Mitoxana® (ASTA) cancer cells in Medical) in general proliferate without Thiotepa (Bedford, Abraxis, restrictions beyond what Teva) that cells do BCNU^ 1,3-bis(2-chloroethyl)-1- healthy, they are Nitosourea more sensitive to damage CCNU^ 1, -(2-chloroethyl)-3- of DNA, and are used cyclohexyl-1-nitrosourea (methyl rental agents in CCNU) clinical form for treating Hexamethylmelamine a variety of (Altretamine, HMM) / Hexalen® tumors. (MGI Pharma Inc.) Busulfan / Mileran (GlaxoSmithKline) Procarbazine HCl / Matulane (Sigma Tau Pharmaceuticals, Inc.) Dacarbazine (DTIC) Chlorambucil / Leukara® (SmithKline Beecham) Melfalan / Alqueran® (GlaxoSmithKline) Cisplatin (Cisplatinum, CDDP) / Platinol (Bristol Myers) Carboplatin / Paraplatin (BMS) Oxaliplatin / Eloxitan® (Sanofi-Aventis USA) Inhibitors of topoisomera sa Inhibitors of topoisomerase are chemotherapeutic agents designed to interfere with the action of enzymes topoisomerases (topoisomerase I and II), which are enzymes that control changes in the structure of DNA by catalysis of breakdown and reunion of the phosphodiester skeleton of the DNA strands during the normal cell cycle. Doxorubicin HCL / Doxil® (Alza) Daunorubicin Citrate / Daunoxome® (Gilead) Mitoxantrone HCL / Novantrone (EMD Serono) Actinomycin D Etoposide / Vepesid® (BMS) / Etopophos® (Hospira, Bedford, Teva Parenteral, Etc.) Topotecan HCL / Hycamtin® (GlaxoSmithKline) Teniposide (VM-26) / Vumon® (BMS) Irinotecan HCL(CPT-ll) / Camptosar® (Pharmacy & Upjohn) Agents who are Microtubules are one of the Vincristine / Oncovin® (Lilly) they direct to the microtubules components of cytoskeleton. It has a diameter of ~24 nm and a variable length between several micrometers and possibly the millimeters in the axons of nerve cells. microtubules serve as components structural components within cells and are involved in many cellular processes including mitosis, cytokinesis, and vesicular transport. Vinblastine sulfate / Velban®(discontinued) (Lilly) Vinorelbine tartrate / Navelbine® (PierreFabre) Vindesine sulfate / Eldisine® (Lilly) Paclitaxel / Taxol® (BMS) Docetaxel / Taxotere® (Sanofi Aventis USA) Paclitaxel nanoparticles (ABI-007) / Abraxane® (Abraxis BioScience, Inc.) Ixabepilone / IXEMPRA™ (BMS) Kinase inhibitors Tyrosine kinases are enzymes within the cell that function to attach phosphate groups to the amino acid tyrosine. By blocking Imatinib mesylate / Gleevec (Novartis) Sunitinib malate / Sutent® (Pfizer) Sorafenib toslato / Nexavar® (Bayer) the ability to function of the tyrosine proteins These kinases compounds provide a tool to control cell growth cancerous. Nilotinib hydrochloride monohydrate / Tasigna® (Novartis) Inhibitors of protein synthesis It induces apoptosis cellular L-asparaginase / Elspar® (Merck & Co.) Immunotherapeutic agents It induces cancer patients to exhibit an immune response Antibody / Small Molecule Immune System Checkpoint Modulators interferon alpha Angiogenesis inhibitor / Avastin® (Genentech) IL-2 > Interleukin 2 (Aldesleukin) / Proleukin ® (Chiron) IL-12 > Interleukin 12 Therapies with anti-CTLA-4 and PR-1 Yervoy® (ipilimumab; Bristol- Myers Squibb) Opdivo® (nivolumab; Bristol- Myers Squibb) Keytrada® (pembrolizumab; Merck) Hormones Therapies Hormonal treatments associated with menopause and aging aim to increase the amount of certain hormones in your body to to compensate for hormonal declines related to age or related to illness. Hormone therapy as a treatment against Cancer reduces hormone levels specific or alters the cancer's ability to use these Toremifene Citrate / Fareston® (GTX, Inc.) Fulvestrant / Faslodex® (AstraZeneca) Raloxifene HCL / Evista® (Lilly) Anastrozole / Arimidex® (AstraZeneca) Letrozole / Femara® (Novartis) Fadrozol (CGS 16949A ) Exemestane / Aromasin® (Pharmacy & Upjohn) Leuprolide acetate / Eligard® (QTL USA) Lupron® (TAP Pharm) Goserelin acetate / Zoladex® (AstraZeneca) Triptorelin pamoate / Trelstar® (Watson Labs) Buserelin / Suprefact® (Sanofi Aventis) hormones for their growth and dispersion. Nafarelin Synarel® (Pfizer) Cetrorelix / Cetrotide® (EMD Serono) Bicalutamide / Casodex® (AstraZeneca) Nilutamide / Nilandron® (Aventis Pharm.) Megestrol acetate / Megace® (BMS) Somatostatin Analogues (Octreotide acetate / Sandostatin® (Novartis) Glucocorticoids from Drugs anti-inflammatories They are used to reduce inflammation and pain from cancer. Prednisolone Dexamethasone / Decadron® (Wyeth) Inhibitors of Aromatase Includes imidazoles Ketoconazole Inhibitors of mTOR The mTOR signaling pathway was originally discovered in agent studies Sirolimus (Rapamycin) / Rapamune® (Wyeth) Temsirolimus (CCI-779) / Torisel® (Wyeth) The immunosuppressant rapamycin. This highly conserved pathway regulates cell proliferation and metabolism in response to environmental factors, connecting the cell growth factor receptor pathway via phosphoinositide-3-kinase (PI-3K) with cell growth, proliferation, and angiogenesis. Deforolimus (AP23573) / (Ariad Pharm.) Everolimus (RAD00I) / Certican® (Novartis) In addition to the anticancer agents mentioned previously, the anti-EGFR antibodies and ADCs described herein may be administered in combination with the agents described in Section II. Furthermore, the anticancer agents mentioned previously may also be used in the ADCs of the invention. In certain formulations, anti-EGFR antibodies or anti-adrenergic dendritic cells (ADCs) can be administered alone or with another antineoplastic agent that acts in conjunction or synergistically with the antibody to treat the disease associated with EGFR activity. Such anticancer agents include, for example, For example, agents well known in the art (e.g., cytotoxins, chemotherapeutic agents, small molecules, and radiation). Examples of anticancer agents include, but are not limited to, Panorex (Glaxo-Welcome), Rituxan (IDEC / Genentech / Hoffman la Roche), Milotarg (Wyeth), Campath (Millennium), Zevalin (IDEC and Schering AG), Bexxar (Corixa / GSK), Erbitux (Imclone / BMS), Avastin (Genentech), and Herceptin (Genentech / Hoffman la Roche). Other anticancer agents include, but are not limited to, those disclosed in U.S. Patent No. 7,598,028 and International Publication No. WO2008 / 100624, the contents of which are incorporated herein by reference. One or more anticancer agents may be administered simultaneously or before or after the administration of an antibody or antigen-binding portion thereof of the invention. In particular embodiments of the invention, the anti-EGFR antibodies or ADCs described herein can be used in combination therapy with an apoptotic agent, such as a bcl-xl inhibitor or a Bcl-2 (B-cell lymphoma 2) inhibitor (e.g., ABT-199, venetoclax), to treat cancer, such as leukemia, in a subject. In one embodiment, the anti-EGFR antibodies or ADCs described herein can be used in combination therapy with a bcl-xl inhibitor to treat cancer. In another embodiment, the anti-EGFR antibodies or ADCs described herein can be used in combination therapy with venetoclax to treat cancer. In particular embodiments of the invention, the anti-EGFR antibodies or ADCs described herein can be used in therapy in combination with a NAMPT inhibitor (see examples of inhibitors in U.S. Patent 2013 / 0303509; AbbVie, Inc., which is incorporated herein by reference) to treat a subject in need. NAMPT (also known as pre-B cell colony-enhancing factor (PBEF) and visfatin) is an enzyme that catalyzes the phosphoribosylation of nicotinamide and is the rate-limiting enzyme in one of two NAD salvage pathways. In one embodiment of the invention, the anti-EGFR antibodies and ADCs described herein are administered in combination with a NAMPT inhibitor for the treatment of cancer in a subject. In particular embodiments of the invention, the anti-EGFR antibodies or ADCs described herein can be used in combination therapy with SN-38, which is the active metabolite of the topoisomerase inhibitor irinotecan. In other embodiments of the invention, the anti-EGFR antibodies or ADCs described herein can be used in combination therapy with a PARP (poly ADP ribose polymerase) inhibitor, for example, veliparib, to treat cancer, including breast, ovarian, and non-small cell lung cancer. Other examples of additional therapeutic agents that may be co-administered and / or formulated with the anti-EGFR antibodies or anti-EGFR ADCs described herein include, but are not limited to, one or more of: inhaled steroids; beta agonists, e.g., short-acting or long-acting beta agonists; leukotriene or leukotriene receptor antagonists; combination drugs such as ADVAIR; IgE inhibitors, e.g., anti-IgE antibodies (e.g., XOLAIR®, omalizumab); Phosphodiesterase inhibitors (e.g., PDE4 inhibitors); xanthines; anticholinergic drugs; mast cell stabilizing agents such as cromolyn; IL-4 inhibitors; IL-5 inhibitors; eotaxin / CCR3 inhibitors; histamine antagonists or antagonists of histamine receptors, including H1, H2, H3, and H4; and prostaglandin D antagonists or antagonists of prostaglandin D receptors (DP1 and CRTH2). Such combinations may be used to treat, for example, asthma and other respiratory disorders. Other examples of additional therapeutic agents that may be co-administered and / or formulated with the anti-EGFR antibodies or anti-EGFR ADCs described herein include, but are not limited to, one or more of temozolomide, ibrutinib, duvelisib, and idelalisib.Other examples of therapeutic agents that may be co-administered and / or formulated with one or more anti-EGFR antibodies or fragments thereof include one or more of: TNF antagonists (e.g., a soluble fragment of a TNF receptor, e.g., human TNF receptor p55 or p75 or derivatives thereof, e.g., 75 kD TNFR-IgG (75 kD TNF receptor-IgG fusion protein, ENBREL)); TNF enzyme antagonists, e.g., TNF-converting enzyme (TACE) inhibitors; muscan receptor antagonists; TGF-beta antagonists; interferon gamma; perfenidone; chemotherapeutic agents, e.g., methotrexate, leflunomide, or sirolimus (rapamycin) or an analogue thereof, e.g., CCI-779, COX2, and cPLA2 inhibitors; NSAIDs; immunomodulators; p38 inhibitors, TPL-2, MK-2 and NFkB inhibitors, among others. Other preferred combinations are cytokine-suppressing anti-inflammatory drugs (CSAIDs); antibodies against, or antagonists of, other human cytokines or growth factors, for example, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-15, IL-16, IL-18, IL-21, IL-31, interferons, EMAP-II, GM-CSF, FGF, EGF, PDGF, and edotelin-1, as well as the receptors for these cytokines and growth factors. The antibodies of the invention, or antigen-binding portions thereof, can be combined with antibodies against cell surface molecules such as CD2, CD3, CD4, CD8, CD25, CD28, CD30, CD40, CD45, CD69, CD80 (B7.1), CD86 (B7.2), CD90, CTLA, CTLA-4, PD-1, or their ligands, including CD154 (gp39 or CD40L). Preferred combinations of therapeutic agents can interfere at different points in the inflammatory cascade; preferred examples include TNF antagonists such as chimeric, humanized, or human TNF antibodies, adalimumab (HUMIRA; D2E7; PCT Publication No. WO 97 / 29131 and U.S. Patent No. 6,090,382, which is incorporated herein by reference), CA2 (Remicade™), CDP 571, and soluble TNF receptors p55 or p75, or derivatives thereof (p75TNFR1gG (Enbrel™) or p55TNFR1gG (Lenercept)), and also TNF-converting enzyme (TACE) inhibitors; similarly, IL-1 inhibitors (interleukin-1 converting enzyme inhibitors, IL-1RA, etc.) may be effective for the same reason. Other preferred combinations include interleukin-4. The pharmaceutical compositions of the invention may include a “therapeutically effective amount” or a “prophylactically effective amount” of an antibody or antibody portion of the invention. A “therapeutically effective amount” refers to an effective quantity, dosage, and time period necessary to achieve the desired therapeutic result. A therapeutically effective amount of the antibody or antibody portion can be determined by experienced persons. In the art, the therapeutically effective amount can vary according to factors such as the stage of the disease, the individual's age, sex, and weight, and the ability of the antibody or antibody portion to produce a desired response in the individual. A therapeutically effective amount is also one in which any toxic or harmful effects of the antibody or antibody portion are outweighed by the beneficial therapeutic effects. A "prophylactically effective amount" refers to an effective quantity, dosage, and time period required to achieve the desired prophylactic result. Typically, since a prophylactic dose is used in subjects before or at an earlier stage of the disease, the prophylactically effective amount will be less than the therapeutically effective amount. Dosage regimens can be adjusted to provide the desired optimal response (e.g., a therapeutic or prophylactic response). For example, a single bolus may be administered, several doses may be given at intervals, or the dose may be reduced or increased proportionally as required by the therapeutic situation. It is particularly advantageous to formulate parenteral compositions in a unit-dose form to facilitate administration and ensure greater dosage uniformity. The term "unit-dose form," as used herein, refers to physically discrete units suitable for individual dosing in mammalian subjects; each unit contains a predetermined amount of the active compound, calculated to produce the desired therapeutic effect in conjunction with the required carrier drug.The specification for the individual dosage form of the invention is dictated and dependent. directly from (a) the unique characteristics of the active compound and the particular therapeutic or prophylactic effect that is desired, and (b) the inherent limitations in the art of compositions of such an active compound for the treatment of sensitivity in individuals. By way of example, a non-limiting range for a prophylactically or therapeutically effective amount of an ADC, antibody, or antibody portion of the invention is between 0.1 and 20 mg / kg, more preferably between 1 and 10 mg / kg. In one embodiment, the dose of the antibodies and ADCs described herein is between 1 and 6 mg / kg, including the individual doses mentioned, for example, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, and 6 mg / kg. In another embodiment, the dose of the antibodies and ADCs described herein ranges from 1 to 200 pg / kg, including the individual doses mentioned, for example, 1 pg / kg, 2 pg / kg, 3 pg / kg, 4 pg / kg, 5 pg / kg, 10 pg / kg, 20 pg / kg, 30 pg / kg, 40 pg / kg, 50 pg / kg, 60 pg / kg, 80 pg / kg, 100 pg / kg, 120 pg / kg, 140 pg / kg, 160 pg / kg, 180 pg / kg, and 200 pg / kg. It should be noted that the dose values ​​may vary depending on the type and severity of the condition being treated.It should also be understood that, for a particular subject, specific dosage regimens should be adjusted over time according to individual need and the professional judgment of the person in charge of administering or supervising the administration of the compositions, and that the dosage ranges indicated herein are presented only as examples and are not to limit the scope or practice of the claimed composition. In one embodiment, an anti-EGFR antibody described herein, for example, AbA, or an antigen-binding potion thereof, is It is administered to a subject who needs it, for example, a subject with cancer, as an ADC at a dose of between 0.1 and 30 mg / kg. In another embodiment, the anti-EGFR antibody, for example, AbA, or an antigen-binding solution thereof, is administered to a subject who needs it, for example, a subject with cancer, as an ADC at a dose of between 1 and 15 mg / kg. In another embodiment, the anti-EGFR antibody, for example, AbA, or an antigen-binding solution thereof, is administered to a subject who needs it, for example, a subject with cancer, as an ADC at a dose of between 1 and 10 mg / kg. In another embodiment, the anti-EGFR antibody, for example, AbA, or an antigen-binding portion thereof, is administered to a subject in need, for example, a subject with cancer, as an ADC at a dose of between 2 and 3 mg / kg. In one embodiment, an anti-EGFR antibody described herein, for example, AbA, or an antigen-binding portion thereof, is administered to a subject in need, for example, a subject with cancer, as an ADC at a dose of between 1 and 200 pg / kg. In another embodiment, the anti-EGFR antibody, for example, AbA, or an antigen-binding portion thereof, is administered to a subject in need, for example, a subject with cancer, as an ADC at a dose of between 5 and 150 pg / kg. 100 pg / kg. In another embodiment, the anti-EGFR antibody, for example, AbA, or an antigen-binding portion thereof, is administered to a subject in need, for example, a subject with cancer, as an ADC at a dose of between 5 and 90 pg / kg. In another embodiment, the anti-EGFR antibody, for example, AbA, or an antigen-binding portion thereof, is administered to a subject in need, for example, a subject with cancer, as an ADC at a dose of between 5 and 80 pg / kg. In another embodiment, the anti-EGFR antibody, for example, AbA, or an antigen-binding portion thereof, is administered to a subject in need, for example, a subject with cancer, as an ADC at a dose of between 5 and 70 pg / kg.In another embodiment, the anti-EGFR antibody, for example, AbA, or an antigen-binding portion thereof, is administered to a subject in need, for example, a subject with cancer, as an ADC at a dose of between 5 and 60 pg / kg. In another embodiment, the anti-EGFR antibody, for example, AbA, or an antigen-binding portion thereof, is administered to a subject in need, for example, a subject with cancer, as an ADC at a dose of between 10 and 80 pg / kg. In one embodiment, an anti-EGFR ADC described herein, e.g., AbA-vc-MMAE, is administered to a subject in need, e.g., a subject with cancer, at a dose of between 0.1 and ...

Claims

1. An anti-human epidermal growth factor receptor (anti-hEGFR) antibody characterized in that it comprises: a heavy chain variable region comprising the amino acid sequence described in SEQ ID NO: 9, and a light chain variable region comprising the amino acid sequence described in SEQ ID NO: 5; a heavy chain CDR3 domain comprising the amino acid sequence described in SEQ ID NO: 12, a heavy chain CDR2 domain comprising the amino acid sequence described in SEQ ID NO: 11, and a heavy chain CDR1 domain comprising the amino acid sequence described in SEQ ID NO: 10; and a light chain CDR3 domain comprising the amino acid sequence described in SEQ ID NO: 8, a light chain CDR2 domain comprising the amino acid sequence described in SEQ ID NO: 7, and a light chain CDR1 domain comprising the amino acid sequence described in SEQ ID NO: 6, wherein the antibody is an IgG isotype.Four more claims follow.