Anti-her2 antibody for use in treating a low her2 expressing tumor in a subject

Abstract

In one aspect, the present invention relates to an anti-HER2 immunoglobulin E (IgE) antibody for use in treating a low HER2-expressing tumor in a subject. In another aspect, immunoglobulins that bind to HER2 are provided.

Description

[0001]COMPOSITION FIELD OF THE INVENTION The present invention relates to the field of therapeutic antibodies and uses thereof and in particular to immunoglobulin E (IgE) antibodies for use in treating cancer. The present invention also relates to methods of treating diseases such as cancer using such IgE antibodies. BACKGROUND Therapeutic antibodies now complement conventional treatments for a number of malignant diseases, but almost all agents currently developed rely on only one of the nine human antibody classes, namely IgGı, the most abundant antibody class in the blood (Weiner LM, Surana R, Wang S (2010) Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 10: 317-327). The human immune system naturally deploys nine antibody classes and subclasses (IgM, IgD, IgG1-4, IgAl , IgA2 and IgE) to perform immune surveillance and to mediate destruction of pathogens in different anatomical compartments. Yet only IgG (most often IgG1) has been applied in immunotherapy of cancers. One reason may be that IgG antibodies (particularly IgG1), constitute the largest fraction of circulating antibodies in human blood. The choice of antibody class is also based on pioneering work in the late 1980s, comparing a panel of chimaeric antibodies of the same specificity, each with Fc regions belonging to one of the nine antibody classes and subclasses (Bruggemann M, Williams GT, Bindon CI, Clark MR, Walker MR, Jefferis R, Waldmann H, Neuberger MS (1987) Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med 166: 1351-1361). Antibodies were evaluated for their ability to bind complement and their potency to mediate haemolysis and cytotoxicity of antigen- expressing target cells in the presence of complement. IgG1 in combination with human peripheral blood mononuclear cells (PBMC) was the most effective IgG subclass in complement-dependent cell killing in vitro, while the IgA and IgE antibodies were completely inert. Subsequent clinical trials with antibodies recognising the B cell marker CD20 supported the inference that IgG1 would be the subclass best suited for immunotherapy of patients with B cell malignancies such as non-Hodgkin’s lymphoma (Alduaij W, Illidge TM (2011) The future of anti-CD20 monoclonal antibodies: are we making progress? Blood 117: 2993-3001). Since those studies, comparisons of anti-tumour effects by different antibody classes have been confined to IgG and IgM in both murine models and patients with lymphoid malignancies, while IgA has been shown to mediate ADCC in vitro and in vivo in mouse models of lymphoma (Dechant M, Valerius T (2001) IgA antibodies for cancer therapy. Crit Rev Oncol Hematol 39: 69-77). The HER family of receptor tyrosine kinases are important mediators of cell growth, differentiation and survival. The receptor family includes four distinct members including epidermal growth factor receptor (EGFR, ErbB1, or HER1), HER2 (ErbB2 or pl85neu), HER3 (ErbB3) and HER4 (ErbB4 or tyro2). EGFR, encoded by the erbB1 gene, has been causally implicated in human malignancy. In particular, increased expression of EGFR has been observed in breast, bladder, lung, head, neck and stomach cancer as well as glioblastomas. Increased EGFR receptor expression is often associated with increased production of the EGFR ligand, transforming growth factor alpha (TGF-α), by the same tumor cells resulting in receptor activation by an autocrine stimulatory pathway (Baselga and Mendelsohn, Pharmac. Ther. 64:127-154 (1994)). Monoclonal antibodies directed against the EGFR or its ligands, TGF-α and EGF have been evaluated as therapeutic agents in the treatment of such malignancies (see e.g., Baselga and Mendelsohn., supra; Masui et al. Cancer Research 44:1002-1007 (1984); and Wu et al. J. Clin. Invest. 95:1897-1905 (1995)). The second member of the HER family, i.e. HER2, was originally identified as the product of the transforming gene from neuroblastomas of chemically treated rats. The activated form of the neu proto-oncogene results from a point mutation (valine to glutamic acid) in the transmembrane region of the encoded protein. Amplification of the human homolog of neu is observed in breast and ovarian cancers and correlates with a poor prognosis (Slamon et al. , Science, 235: 177-182 (1987); Slamon et al. , Science, 244:707-712 (1989); and US Pat No. 4,968,603). Overexpression of HER2 (frequently but not uniformly due to gene amplification) has also been observed in other carcinomas including carcinomas of the stomach, endometrium, salivary gland, lung, kidney, colon, thyroid, pancreas and bladder (see e.g. Ross et al Cancer 79:2162-70 (1997); and Sadasivan et al J. Urol.150:126-31 (1993)). IgG antibodies directed against human HER2 protein products have been described. See, for example, Drebin et al, Cell 41:695-706 (1985) and U.S. Patent 5,824,311. Hudziak et al, Mol. Cell. Biol.9(3): 1165-1172 (1989) describe the generation of a panel of HER2 antibodies which were characterized using the human breast tumor cell line SKBR-3. The antibody 4D5 was further found to sensitize HER2- overexpressing breast tumor cell lines to the cytotoxic effects of TNF-α (see U.S. Patent 5,677,171). A recombinant humanized version of the murine IgG anti-HER2 antibody 4D5 (huMAb4D5-8, rhuMAb HER2, Trastuzumab or HERCEPTIN® was shown to be effective in patients with HER2-overexpressing metastatic breast cancers that have received extensive prior anti-cancer therapy (Baselga et al, J. Clin. Oncol.14:737-744 (1996)). Trastuzumab received marketing approval from the US Food and Drug Administration in 1998 for the treatment of patients with metastatic breast cancer whose tumors overexpress the HER2 protein. Other anti-HER2 IgG antibodies with various properties have been described in e.g. Tagliabue et al. Int. J. Cancer 47:933-937 (1991); WO94 / 00136; U.S. Patent 5,783,186; and Klapper et al. Oncogene 14:2099-2109 (1997). Homology screening has resulted in the identification of other HER receptor family members, including HER3 (see US Patents 5,183,884 and 5,480,968) and HER4 (Plowman et al, Nature, 366:473-475 (1993)). Both of these receptors display increased expression on at least some breast cancer cell lines. The HER receptors are generally found in various combinations in cells and heterodimerization is thought to increase the diversity of cellular responses to a variety of HER ligands. For instance, EGF stimulates EGFR and HER2 to form a heterodimer, which activates EGFR and results in transphosphorylation of HER2 in the heterodimer. Dimerization and / or transphosphorylation appears to activate the HER2 tyrosine kinase. See Earp et al., supra. Likewise, when HER3 is co-expressed with HER2, an active signaling complex is formed and antibodies directed against HER2 are capable of disrupting this complex (Sliwkowski et al, J. Biol. Chem., 269(20): 14661-14665 (1994)). To target the HER signaling pathway, rhuMAb 2C4 (Pertuzumab, PERJETA™) was developed as a humanized IgG antibody that inhibits the dimerization of HER2 with other HER receptors, thereby inhibiting ligand-driven phosphorylation and activation, and downstream activation of the RAS and AKT pathways. Pertuzumab binds to subdomain II (the dimerization region) of the extracellular part of the HER2 receptor, in contrast to trastuzumab, which binds to subdomain IV (the juxtamembrane region). Pertuzumab received US FDA approval for the treatment of HER2-overexpressing metastatic breast cancer in 2012. Pertuzumab may also be administered in combination with trastuzumab and docetaxel for the same indication. Antibodies of the IgE class play a central role in allergic reactions and have many properties that may be advantageous for cancer therapy. IgE-based active and passive immunotherapeutic approaches have been shown to be effective in both in vitro and in vivo models of cancer, suggesting the potential use of these approaches in humans (Leoh et al., Curr Top Microbiol Immunol.2015; 388: 109–149). Thus IgE therapeutic antibodies may offer enhanced immune surveillance and superior effector cell potency against cancer cells. Karagiannis et al.2009 (Cancer Immunol Immunother.2009 June; 58(6): 915–930) described an engineered IgE comprising the same light- and heavy-chain variable-regions as trastuzumab IgG, but with an epsilon (i.e. IgE heavy chain constant region) in place of the IgG gamma-1 heavy chain constant region of trastuzumab. Trastuzumab IgE was shown to trigger antibody- dependent cell-mediated cytotoxicity (ADCC) and trigger mast cell degranulation in the presence of HER2-expressing tumour cells, and to mediate comparable levels of tumour cell growth arrest to trastuzumab IgG. A fully human anti-HER2 IgE has also been developed using the variable regions of the single- chain Fv C6MH3-B1 (Daniels TR et al (2012) Targeting HER2 / neu with a fully human IgE to harness the allergic reaction against cancer cells. Cancer Immunol Immunother.61: 991–1003). C6MH3-B1 induced in vitro degranulation of RBL SX-38 cells expressing human FcεRI in the presence of murine mammary carcinoma cells expressing human HER2 / neu (D2F2 / E2) but not in the presence of the parental D2F2 cells that lack HER2 / neu expression or shed (soluble) extracellular domain of HER2 / neu(ECDHER2). These results suggest that anti-HER2 IgE could trigger an acute inflammatory response (type I hypersensitivity) within the tumour microenvironment, where the HER2 / neu antigen is overexpressed at high levels on the surface of cancer cells (Pegram M, Ngo D. (2006) Application and potential limitations of animal models utilized in the development of trastuzumab (Herceptin): a case study. Adv Drug Deliv Rev.58: 723–734.), facilitating FcεRI cross-linking and triggering effector cell degranulation. The known IgG anti-HER2 antibodies currently in clinical use (e.g. trastuzumab and pertuzumab) are only effective at treating cancers with high HER2 expression. For this reason, one of the challenges in the development of anti-HER2 antibodies was to identify and select a patient population likely to respond to the drug. It was therefore necessary to develop an accurate and reliable diagnostic assay for detection of HER2 protein overexpression in the tumour. In the clinical development of trastuzumab, a clinical trial assay (CTA), developed by Genentech, was initially used for selection of HER2 positive patients, whilst during a phase III trial with trastuzumab, a new optimized IHC assay, HercepTest™ was designed and developed by Dako. In September 1998, the Food and Drug Administration (FDA) simultaneously granted approval to trastuzumab and HercepTest™. HercepTest™ thus became the first companion diagnostic ever approved by the FDA. The FDA also approved specific immunohistochemistry (IHC) scoring criteria for the assay, which required a strong complete membrane staining in more than 10% of the tumour cells (classified as HER2 IHC3+) in order for trastuzumab therapy to be indicated. This staining requirement has been used in all pivotal cancer trials with trastuzumab, including in metastatic and adjuvant indications, and subsequently also in relation to other HER2 inhibitors, such as pertuzumab and antibody-drug conjugates such as ado-trastuzumab emtansine (see Jørgensen et al., (2021) Front. Oncol. 11:676939; Nicolo et al. Ther Adv Med Oncol 2023, Vol.15: 1 –16). However many cancer patients (including more than half of those with breast cancer) express low levels of HER2 in their tumours, e.g. having an immunohistochemical assay classification of IHC2+ or lower. For this sub-group of subjects, known anti-HER2-based therapies are not indicated and not effective. There thus remains a clear unmet need for new treatments that can target cancers, including breast cancer, with low HER2 expression. SUMMARY OF THE INVENTION Accordingly, in one aspect the present invention provides an anti-HER2 immunoglobulin E (IgE) antibody for use in treating a low HER2-expressing tumor in a subject. In one embodiment, less than 10% of tumor cells in a sample from the subject show strong complete membrane staining for HER2 using immunohistochemical detection of HER2. Preferably no tumor cell cluster (5 or more cells) showing strong complete membrane staining for HER2 is present. In one embodiment, using immunohistochemical detection of HER2, at least 10% of tumor cells or a tumor cell cluster (5 or more cells) in a sample from the subject show weak to moderate complete membrane staining for HER2. In another embodiment, at least 10% of tumor cells or a tumor cell cluster (5 or more cells) in a sample from the subject show faint or barely perceptible partial membrane staining for HER2. In one embodiment, immunohistochemical detection of HER2 in a sample from the subject is performed using a Dako anti-HER2 immunohistochemistry system (HercepTest™). In some embodiments, a tumor sample from the subject has a HER2 immunohistochemical staining (HER2 IHC) score of 2+ or lower (e.g.2+, 1+ or 0), more preferably 2+ or 1+. In some embodiments, amplification of a HER2-encoding gene (erbB2) is analysed in a tumor sample from the subject, e.g. using fluorescence in situ hybridization (FISH), and optionally erbB2 copy number is reported relative to the copy number of a centromere 17 (CEN17). In some embodiments, the tumor has a HER2 / CEN17 ratio < 2.0 or shows no detectable erbB2 gene amplification as determined by FISH. In some embodiments, tumor HER2 expression in the subject is lower than in at least 50% of cancer subjects. Preferably membrane HER2 expression in tumor cells of the subject is lower than in at least 60%, at least 70% or at least 80% of subjects suffering from the same form of cancer; more preferably wherein tumor HER2 expression in the subject is lower than in at least 50%, at least 70% or at least 90% of HER2-expressing tumors (preferably HER2-expressing breast tumors). In some embodiments, the tumor expresses HER2. Preferably at least 1%, 5%, 10%, 15% or 20% of tumor cells in the subject show detectable membrane HER2 expression using immunohistochemical detection of HER2. In one embodiment, the antibody binds to subdomain II of the extracellular domain of the HER2. Preferably the antibody at least partially competes with pertuzumab IgG for binding to HER2. In another embodiment, the antibody binds to subdomain IV of the extracellular domain of the HER2. Preferably the antibody at least partially competes with trastuzumab IgG for binding to HER2. In further embodiments the antibody may comprise an amino acid sequence as defined in any one of SEQ ID NO:s 1 to 10, .e.g. the antibody may comprise trastuzumab IgE. In further embodiments the antibody may comprise an amino acid sequence as defined in any one of SEQ ID NO:s 11 to 40. For instance, the antibody may comprise one to six CDR sequences selected from one of the following groups: (i) SEQ ID NOs: 3, 4, 5, 8, 9 and 10; (ii) SEQ ID NOs: 13, 14, 15, 18, 19 and 20; (iii) SEQ ID NOs: 23, 24, 25, 28, 29 and 30; or (iv) SEQ ID NOs: 33, 34, 35, 38, 39 and 40. Thus the antibody may comprises (i) a heavy chain variable domain sequence as defined in any one of SEQ ID NOs: 2, 12, 22 or 32; (ii) a light chain variable domain sequence as defined in any one of SEQ ID NOs: 7, 17, 27 or 37; (iii) a heavy chain sequence as defined in any one of SEQ ID NOs: 1, 11, 21 or 31; and / or (iv) a light chain sequence as defined in any one of SEQ ID NOs: 6, 16, 26 or 36. In some embodiments, the antibody may be used for treating and / or delaying progression of cancer in the subject. Preferably the tumor or cancer is a breast tumor or cancer, or a gastric tumor or cancer. Most preferably the tumor or cancer is a breast tumor or cancer. In some embodiments, the antibody lacks a cytotoxic moiety. Preferably the antibody is not an antibody-drug conjugate (ADC). In a further aspect, the present invention provides a method for treating and / or delaying progression of cancer in a subject having a low HER2-expressing tumor, the method comprising a step of administering an anti-HER2 immunoglobulin E (IgE) antibody as defined herein to the subject in a therapeutically-effective amount. In another aspect, the present invention provides a pharmaceutical composition for use in treating a low HER2-expressing tumor in a subject, comprising an anti-HER2 immunoglobulin E (IgE) antibody as defined herein and one or more pharmaceutically acceptable excipients, carriers or diluents. In a further aspect, the present invention provides an immunoglobulin, or a functional fragment thereof, comprising comprises one to six CDR sequences selected from: (i) SEQ ID NOs: 13, 14, 15, 18, 19 and 20; (ii) SEQ ID NOs: 23, 24, 25, 28, 29 and 30; or (iii) SEQ ID NOs: 33, 34, 35, 38, 39 and 40. In one embodiment, the immunoglobulin comprises: (i) a heavy chain variable domain sequence as defined in any one of SEQ ID NOs: 12, 22 or 32; (ii) a light chain variable domain sequence as defined in any one of SEQ ID NOs: 17, 27 or 37; (iii) a heavy chain sequence as defined in any one of SEQ ID NOs: 11, 21 or 31; and / or (iv) a light chain sequence as defined in any one of SEQ ID NOs: 6, 16, 26 or 36. Preferably the immunoglobulin is of isotype IgE, e.g. the antibody comprises one or more Cε1, Cε2, Cε3 and / or Cε4 domains, or variants or functional fragments thereof. Preferably the immunoglobulin comprises at least Cε2, Cε3 and / or Cε4 domains. In some embodiments, the immunoglobulin is a chimaeric or humanized antibody. For instance the immunoglobulin may comprise (i) one or more human framework regions; and / or (ii) one or more human IgE heavy and / or light chain constant domains. Preferably the immunoglobulin comprises human Cε1, Cε2, Cε3 and / or Cε4 domains. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows levels of HER2 expression on the surface of JIMT1 and SKBR3 cell lines analysed using flow cytometry. Figure 2 shows anti-tumour efficacy of a HER2-targeting IgE, Trastuzamab-IgE, against JIMT1 tumours in a PBMC humanised mouse model. Figure 3 shows levels of HER2 expression on the surface of MTLn3 cells analysed using flow cytometry. Figure 4 shows anti-tumour efficacy of anti-HER2 IgE antibodies V20, V23 and V26 against MTLn3 tumours in a syngeneic Fischer 344 rat model Figure 5 shows immune cell infiltration into MTLn3 tumors in rats after control (PBS) or V26 IgE antibody treatment. Figure 6 shows immune cell (monocyte and neutrophil) infiltration and appearance of apoptotic cells in MTLn3 tumors in rats after control (PBS) or V26 IgE antibody treatment. Figure 7 shows increased MTLn3 tumor cell death in rats after control (PBS) or V26 IgE antibody treatment. Figure 8 shows that an anti HER2 IgE (V26, referred to in Fig.8 as EPS226) has anti-tumour activity in a triple negative breast cancer model in mice in vivo. DETAILED DESCRIPTION OF THE INVENTION It has surprisingly been found that anti-HER2 IgE antibodies can significantly inhibit the growth of low HER2-expressing tumors in vivo. In particular, in syngeneic rat and immunodeficient humanized mouse models anti-HER2 IgE antibodies showed high efficacy against tumor cells corresponding to HER2 IHC 1+ and 2+ HercepTest scores. Thus anti- HER2 IgE may be used to treat or delay progression of cancer in subjects having a low HER2 membrane expression score. This finding is particularly surprising because anti-HER2 IgG antibodies (e.g. trastuzumab and pertuzumab) are typically only indicated for treatment of high HER2-expressing tumors (e.g. classified as HER2 IHC3+ using HercepTest™). Thus anti-HER2 treatment approaches using IgG antibodies have focussed on treating high HER2 expressors and / or combination of the antibody with a cytotoxic moiety, e.g. in an antibody-drug conjugate (ADC). For instance, ado-trastuzumab emtansine (Kadcyla®, Roche / Genentech) is an antibody-drug conjugate consisting of trastuzumab IgG covalently linked to the cytotoxic agent DM1. However this ADC still showed poor activity against breast cancers with low HER2 expression. Newer anti-HER2 IgG ADCs have been developed. These include trastuzumab deruxtecan (Enhertu™, trastuzumab IgG conjugated through a tetrapeptide-based cleavable linker with the topoisomerase I inhibitor deruxtecan), trastuzumab duocarmazine (trastuzumab IgG bound to a DNA-alkylating duocarmycin payload through a cleavable linker), disitamab vedotin (an anti-HER2 IgG humanized antibody, hertuzumab, conjugated to a microtubule inhibitor monomethyl auristatin E (MMAE) payload through a cleavable linker), and MRG002 (modified trastuzumab IgG conjugated through a cleavable linker to a MMAE payload). Thus it has been suggested that a way to target low HER2-expressing tumors is to use such anti- HER2 IgG ADCs that carry a more potent cytotoxic payload or higher drug-to-antibody ratio (DAR) than ado-trastuzumab emtansine, or that have the ability to elicit the so-called bystander effect (see Nicolo et al. Ther Adv Med Oncol 2023, Vol.15: 1 –16). On the other hand, many ADCs show excessive toxicities and unfavourable risk-benefit profiles. A substantial fraction of treated patients may require dose reduction, treatment delays, or treatment discontinuation due to intolerable ADC-associated toxicity. This often limits ADC dosage to levels below those required for optimal anti-cancer effects (see e.g. Nguyen et al., Cancers (Basel).2023 Feb; 15(3): 713). In contrast, as demonstrated herein anti-HER2 IgE antibodies are capable of inhibiting growth of low HER2-expressing tumors in vivo as a monotherapy, i.e. without incorporation into an ADC or combination with a further chemotherapeutic drug. This can avoid the disadvantages of ADCs and in particular may lead to reduced toxicity, improved tolerability and an improved safety profile. Therefore the present invention provides a significant contribution to the art in addressing an unmet medical need, specifically in a sub-group of cancer patients who are low HER2 expressors. Therapeutic antibody Antibodies are polypeptide ligands comprising at least a light chain or heavy chain immunoglobulin variable region which specifically recognizes and specifically binds an epitope of an antigen, such as HER2, or a fragment thereof. Antibodies are typically composed of a heavy and a light chain, each of which has a variable region, termed the variable heavy (VH) region and the variable light (VL) region. Together, the VH region and the VL region are responsible for binding the antigen recognized by the antibody. Antibodies include intact immunoglobulins and the variants and portions of antibodies well known in the art, provided that such fragments retain at least one function of IgE, e.g. are capable of binding an Fcɛ receptor. Antibodies also include genetically engineered forms such as chimaeric, humanized (for example, humanized antibodies with murine sequences contained in the variable regions) or human antibodies, heteroconjugate antibodies (such as, bispecific antibodies), e.g. as described in Kuby, J., Immunology, 3rd Ed., W.H. Freeman & Co., New York, 1997. Typically, a naturally occurring immunoglobulin has heavy (H) chains and light (L) chains interconnected by disulfide bonds. There are two types of light chain, lambda (λ) and kappa (k). There are nine main isotypes or classes which determine the functional activity of an antibody molecule: IgA1-2, IgD, IgE, IgG1-4 and IgM, corresponding to the heavy chain types α, δ, ɛ, γ, and μ. Thus, the type of heavy chain present defines the class of antibody. Distinct heavy chains differ in size and composition; ɑ and γ contain approximately 450 amino acids, while µ and ɛ have approximately 550 amino acids. The differences in the constant regions of each heavy chain type account for the different effector functions of each antibody isotype, by virtue of their selective binding to particular types of receptor (e.g. Fc receptors). Accordingly, in embodiments of the present invention the antibody preferably comprises an epsilon (ɛ) heavy chain, i.e. the antibody is of the isotype IgE which binds to Fcɛ receptors. Each heavy and light chain contains a constant region and a variable region, (the regions are also known as “domains”). In combination, the heavy and the light chain variable regions specifically bind the antigen. Light and heavy chain variable regions contain a “framework” region interrupted by three hypervariable regions, also called “complementarity-determining regions” or “CDRs.” The extent of the framework region and CDRs has been defined (see, Kabat et al., Sequences of Proteins of Immunological Interest, U.S. Department of Health and Human Services, 1991). The Kabat database is now maintained online. The sequences of the framework regions of different light or heavy chains are relatively conserved within a species, such as humans. The framework region of an antibody, that is the combined framework regions of the constituent light and heavy chains, serves to position and align the CDRs in three- dimensional space. The CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3, numbered sequentially starting from the N-terminus, and are also typically identified by the chain in which the particular CDR is located. Thus, a VH CDR3 is located in the variable domain of the heavy chain of the antibody in which it is found, whereas a VL CDR1 is the CDR1 from the variable domain of the light chain of the antibody in which it is found. Antibodies may have a specific VH region and the VL region sequence, and thus specific CDR sequences. Antibodies with different specificities (i.e. different combining sites for different antigens) have different CDRs. Although it is the CDRs that vary from antibody to antibody, only a limited number of amino acid positions within the CDRs are directly involved in antigen binding. These positions within the CDRs are called specificity determining residues (SDRs). References to “VH” refer to the variable region of an immunoglobulin heavy chain. References to “VL” refer to the variable region of an immunoglobulin light chain. A “monoclonal antibody” is an antibody produced by a single clone of B-lymphocytes or by a cell into which the light and heavy chain genes of a single antibody have been transfected. Monoclonal antibodies are produced by methods known to those of skill in the art, for instance by making hybrid antibody-forming cells from a fusion of myeloma cells with immune spleen cells. Monoclonal antibodies include humanized monoclonal antibodies. A “chimaeric antibody” comprises sequences derived from two different antibodies, which are typically derived from different species. For example, chimaeric antibodies may include human and murine antibody domains, e.g. human constant regions and murine variable regions (e.g. from a murine antibody that specifically binds to a target antigen). Chimaeric antibodies are typically constructed by fusing variable and constant regions, e.g. by genetic engineering, from light and heavy chain immunoglobulin genes belonging to different species. For example, the variable segments of the genes from a mouse monoclonal antibody can be joined to human constant segments, such as kappa and epsilon. In one example, a therapeutic chimaeric antibody is thus a hybrid protein composed of the variable or antigen- binding domain from a mouse antibody and the constant or effector domain from a human antibody, e.g. an Fc (effector) domain from a human IgE antibody, although other mammalian species can be used, or the variable region can be produced by molecular techniques. Methods of making chimaeric antibodies are well known in the art, e.g., see U.S. Pat. No.5,807,715. A “humanized” antibody is an antibody including human framework regions and one or more CDRs from a non-human (for example a mouse, rat, or synthetic) antibody. The non-human immunoglobulin providing the CDRs is termed a “donor”, and the human immunoglobulin providing the framework is teamed an “acceptor”. In one embodiment, all the CDRs are from the donor immunoglobulin in a humanized immunoglobulin. The constant regions are typically substantially identical to human immunoglobulin constant regions, i.e., at least about 85-90%, such as about 95% or more identical. Hence, all parts of a humanized immunoglobulin, except the CDRs, are substantially identical to corresponding parts of natural human immunoglobulin sequences. A humanized antibody typically comprises a humanized immunoglobulin light chain and a humanized immunoglobulin heavy chain. A humanized antibody typically binds to the same antigen as the donor antibody that provides the CDRs. The acceptor framework of a humanized immunoglobulin or antibody may have a limited number of substitutions by amino acids taken from the donor framework. Humanized or other monoclonal antibodies can have additional conservative amino acid substitutions which have substantially no effect on antigen binding or other immunoglobulin functions. Humanized immunoglobulins can be constructed by means of genetic engineering (see for example, U.S. Pat. No.5,585,089). Typically humanized monoclonal antibodies are produced by transferring donor antibody complementarity determining regions from heavy and light variable chains of a mouse immunoglobulin into a human variable domain, and then substituting human residues in the framework regions of the donor counterparts. The use of antibody components derived from humanized monoclonal antibodies obviates potential problems associated with the immunogenicity of the constant regions of the donor antibody. Techniques for producing humanized monoclonal antibodies are described, for example, by Jones et al., Nature 321:522, 1986; Riechmann et al., Nature 332:323, 1988; Verhoeyen et al., Science 239:1534, 1988; Carter et al., Proc. Nat’l Acad. Sci. U.S.A. 89:4285, 1992; Sandhu, Crit. Rev. Biotech.12:437, 1992; and Singer et al., J. Immunol.150:2844, 1993. A “human” antibody (also called a “fully human” antibody) is an antibody that includes human framework regions and all of the CDRs from a human immunoglobulin. In one example, the framework and the CDRs are from the same originating human heavy and / or light chain amino acid sequence. However, frameworks from one human antibody can be engineered to include CDRs from a different human antibody. In embodiments of the present invention, the antibodies may be monoclonal or polyclonal antibodies, including chimaeric, humanized or fully human antibodies. Anti-HER2 antibodies In some embodiments, the antibody or immunoglobulin binds specifically to HER2 to form an immune complex. Typically the antibody or immunoglobulin may comprise an antigen-binding region (e.g. one or more variable regions, or one to 6 CDRs) derived from an antibody which is known to bind HER2, preferably human HER2. “HER2” refers to human epidermal growth factor receptor 2. HER2 may also be referred to as receptor tyrosine-protein kinase erbB-2 or CD340 (cluster of differentiation 340). HER2 is encoded in humans by the erbB2 (erythroblastic oncogene B2) or neu gene. Amino acid and nucleotide sequences encoding human HER2 / erbB2 are described in public databases and available e.g. under database accession numbers P04626-1 (UniProt), NM_001005862.3 and NP_001005862.1 (NCBI Ref Seq). Anti-HER2 IgE antibodies, including as humanized trastuzumab IgE (see Table 1 and SEQ ID NOs: 1 to 10) and a fully human anti-HER2 IgE, are known and are described, for example, in Karagiannis et al. (2009), Cancer Immunol Immunother. 58(6): 915–930) and Daniels TR et al. (2012) Cancer Immunol Immunother.61: 991–1003. Further anti-HER2 IgE antibodies are described herein (see Table 1 and SEQ ID NOs: 11 to 40). In one specific embodiment, the antibody comprises a variable region (e.g. a heavy chain variable domain (VH) and / or a light chain variable domain (VL)) or at least one, two, three, four, five or six CDRs (e.g. 3 heavy chain CDRs or 3 light chain CDRs) derived from any known anti-HER2 IgG or IgE antibody. CDR sequences may be defined according to the method of Kabat, Chothia or IMGT (see e.g. Dondelinger, Front Immunol.2018; 9: 2278 and references cited therein, which are incorporated herein by reference). For instance, CDRs may be defined according to Kabat: see Kabat EA, et al. (U.S.) NI of H. Sequences of Immunoglobulin Chains: Tabulation Analysis of Amino Acid Sequences of Precursors, V- regions, C-regions, J-Chain BP-Microglobulins, 1979; or according to Chothia: see Chothia C, et al, Canonical structures for the hypervariable regions of immunoglobulins, J Mol Biol.1987 Aug 20; 196(4):901-1; or according to IMGT: see Giudicelli V et al., IMGT, the international ImMunoGeneTics database, Nucleic Acids Res. 1997 Jan 1; 25(1):206-11 or Lefranc MP, Unique database numbering system for immunogenetic analysis, Immunol Today.1997 Nov; 18(11):509. In one embodiment, the antibody comprises at least one, two, three, four, five or six CDRs (e.g. 3 heavy chain CDRs or 3 light chain CDRs) derived from trastuzumab or pertuzumab. In another embodiment, the antibody or immunoglobulin comprises at least one, two, three, four, five or six CDRs (e.g.3 heavy chain CDRs or 3 light chain CDRs) derived from trastuzumab IgE, V20 IgE, V23 IgE or V26 IgE as described herein, preferably derived from V20 IgE, V23 IgE or V26 IgE, more preferably derived from V23 IgE or V26 IgE, most preferably derived from V26 IgE. For instance, the antibody or immunoglobulin may comprise at least one, two, three, four, five or six CDRs (e.g. 3 heavy chain CDRs or 3 light chain CDRs) selected from one of the following groups (i) SEQ ID NOs: 3, 4, 5, 8, 9 and 10; (ii) SEQ ID NOs: 13, 14, 15, 18, 19 and 20; (iii) SEQ ID NOs: 23, 24, 25, 28, 29 and 30; or (iv) SEQ ID NOs: 33, 34, 35, 38, 39 and 40. In this embodiment, the CDRs may be defined according to the method of Chothia (supra). In another embodiment, the antibody or immunoglobulin comprises at least one, two, three, four, five or six CDRs (e.g.3 heavy chain CDRs or 3 light chain CDRs) present in any one of SEQ ID NOs: 1, 2, 6, 7, 11, 12, 16, 17, 21, 22, 26, 27, 31, 32, 36 or 37, e.g. wherein the CDRs are defined according to the method of Chothia. In another embodiment, the antibody or immunoglobulin comprises (i) a heavy chain variable domain sequence as defined in any one of SEQ ID NOs: 2, 12, 22 or 32; (ii) a light chain variable domain sequence as defined in any one of SEQ ID NOs: 7, 17, 27 or 37; (iii) a heavy chain sequence as defined in any one of SEQ ID NOs: 1, 11, 21 or 31; and / or (iv) a light chain sequence as defined in any one of SEQ ID NOs: 6, 16, 26 or 36. For instance, the antibody or immunoglobulin may comprise: (a) at least one, two, three, four, five or six CDRs selected from SEQ ID NOs: 3, 4, 5, 8, 9 and 10; a heavy and / or light chain variable domain sequence as defined in SEQ ID NO: 2 and / or 7; and / or a heavy and / or light sequence as defined in SEQ ID NO: 1 or 6; (b) at least one, two, three, four, five or six CDRs selected from SEQ ID NOs: 13, 14, 15, 18, 19 and 20; a heavy and / or light chain variable domain sequence as defined in SEQ ID NO: 12 and / or 17; and / or a heavy and / or light sequence as defined in SEQ ID NO: 11 or 16; (c) at least one, two, three, four, five or six CDRs selected from SEQ ID NOs: 23, 24, 25, 28, 29 and 30; a heavy and / or light chain variable domain sequence as defined in SEQ ID NO: 22 and / or 27; and / or a heavy and / or light sequence as defined in SEQ ID NO: 21 or 26; (d) at least one, two, three, four, five or six CDRs selected from SEQ ID NOs: 33, 34, 35, 38, 39 and 40; a heavy and / or light chain variable domain sequence as defined in SEQ ID NO: 32 and / or 37; and / or a heavy and / or light sequence as defined in SEQ ID NO: 31 or 36. In another embodiment, the antibody or immunoglobulin is a chimaeric, humanized or fully human antibody that specifically binds an epitope bound by an anti-HER2 antibody, e.g. trastuzumab, pertuzumab, V20 IgE, V23 IgE or V26 IgE (as defined in Table 1). For instance, the antibody or immunoglobulin may (at least partially) compete with trastuzumab or pertuzumab for binding to human HER2. The (IgE) antibody or immunoglobulin may bind to the same epitope as a known anti-HER2 antibody, or to an epitope (e.g. at least partially) overlapping with that of a known anti-HER2 antibody, or to an epitope in the vicinity of that of a known anti-HER2 antibody (e.g. trastuzumab or pertuzumab). Thus in competition assays, the (IgE) antibody or immunoglobulin may show partial or complete competition with an anti- HER2 antibody (e.g. trastuzumab or pertuzumab) for binding to HER2. Assays for determining competitive binding of antibodies to target antigens, as well as other methods for quantifying binding of antibodies to HER2 are well known in the art and are described for example in Shu et al., Nature Scientific Reports volume 10, Article number: 2986 (2020); Fu et al., MAbs.2014 Jul 1; 6(4): 978–990; Rudkouskaya et al., Molecules.2020 Dec; 25(24): 5976. The antibody or immunoglobulin may bind e.g. to subdomain II or subdomain IV of the extracellular domain of human HER2. In some embodiments, the antibody or immunoglobulin cross-reacts with both human and rodent HER2, e.g. rat and / or mouse HER2. It is demonstrated herein that in a syngeneic rat tumor model, anti-HER2 IgE antibodies showed varying degrees of growth inhibition against HER2 IHC 1+ tumor cells (see e.g. Figure 4). V26 IgE showed the highest anti-tumor effect, followed by V23 IgE, followed by V20 IgE. V26 IgE binds to subdomain II of the extracellular domain of the HER2 and competes with pertuzumab IgG for binding to HER2. V23 IgE binds to subdomain IV of the extracellular domain of the HER2 and competes with trastuzumab IgG for binding to HER2. V20 IgE does not compete with pertuzumab or trastuzumab for binding to HER2. Accordingly, in a preferred embodiment the antibody or immunoglobulin binds to subdomain II of the extracellular domain of the HER2 and / or (at least partially) competes with pertuzumab IgG for binding to HER2, e.g. the antibody or immunoglobulin comprises at least one, two, three, four, five or six CDRs selected from SEQ ID NOs: 33, 34, 35, 38, 39 and 40; a heavy and / or light chain variable domain sequence as defined in SEQ ID NO: 32 and / or 37; and / or a heavy and / or light sequence as defined in SEQ ID NO: 31 or 36. Most preferably, the antibody or immunoglobulin comprises a chimaeric, humanized or fully human antibody that binds to subdomain II of the extracellular domain of the HER2 and / or (at least partially) competes with pertuzumab IgG for binding to HER2. For instance, the antibody or immunoglobulin may be a humanized antibody comprising at least one, two, three, four, five or six CDRs selected from SEQ ID NOs: 33, 34, 35, 38, 39 and 40 and one or more human framework regions and / or one or more human IgE heavy and / or light chain constant domains. Alternatively the antibody or immunoglobulin may be a chimaeric antibody comprising a heavy and / or light chain variable domain sequence as defined in SEQ ID NO: 32 and / or 37 and one or more human IgE heavy and / or light chain constant domains. In an alternative embodiment, the antibody or immunoglobulin binds to subdomain IV of the extracellular domain of the HER2 and / or (at least partially) competes with trastuzumab IgG for binding to HER2, e.g. the antibody or immunoglobulin comprises at least one, two, three, four, five or six CDRs selected from SEQ ID NOs: 23, 24, 25, 28, 29 and 20; a heavy and / or light chain variable domain sequence as defined in SEQ ID NO: 22 and / or 27; and / or a heavy and / or light sequence as defined in SEQ ID NO: 21 or 26. More preferably, the antibody or immunoglobulin comprises a chimaeric, humanized or fully human antibody that binds to subdomain IV of the extracellular domain of the HER2 and / or (at least partially) competes with trastuzumab IgG for binding to HER2. For instance, the antibody or immunoglobulin may be a humanized antibody comprising at least one, two, three, four, five or six CDRs selected from SEQ ID NOs: 23, 24, 25, 28, 29 and 30 and one or more human framework regions and / or one or more human IgE heavy and / or light chain constant domains. Alternatively the antibody or immunoglobulin may be a chimaeric antibody comprising a heavy and / or light chain variable domain sequence as defined in SEQ ID NO: 22 and / or 27 and one or more human IgE heavy and / or light chain constant domains. In one embodiment, the antibody comprises one or more human constant regions, e.g. one or more human heavy chain constant domains (e.g. ɛ constant domains) and / or a human light chain (e.g. к or λ) constant domain. An amino acid sequence of a human heavy chain constant domain is shown in SEQ ID NO:41 (non-bold and non-underlined text present in SEQ ID NO:1). An amino acid sequence of a human light (к) chain constant domain is shown in SEQ ID NO:42 (non-bold and non-underlined text present in SEQ ID NO:6). In one embodiment the antibody comprises one or more human framework regions within the VH and / or VL domains. In one embodiment, the sequence of a humanized immunoglobulin heavy chain variable region framework can be at least about 65% identical to the sequence of the donor immunoglobulin heavy chain variable region framework. Thus, the sequence of the humanized immunoglobulin heavy chain variable region framework can be at least about 75%, at least about 85%, at least about 99% or at least about 95%, identical to the sequence of the donor immunoglobulin heavy chain variable region framework. Human framework regions, and mutations that can be made in a humanized antibody framework regions, are known in the art (see, for example, U.S. Pat. No.5,585,089). Further antibodies against a specific antigen, e.g. HER2, may also be generated by well- established methods, and at least the variable regions or CDRs from such antibodies may be used in the antibodies of the present invention (e.g. the generated antibodies may be used to donate CDR or variable region sequences into IgE acceptor sequences). Methods for synthesizing polypeptides and immunizing a host animal are well known in the art. Typically, the host animal (e.g. a mouse) is inoculated intraperitoneally with an amount of immunogen (e.g. HER2 or a polypeptide comprising an immunogenic fragment thereof), and (in the case of monoclonal antibody production) hybridomas prepared from its lymphocytes and immortalized myeloma cells using the general somatic cell hybridization technique of Kohler, B. and Milstein, C. (1975) Nature 256:495-497. The sequence of human HER2 is well known (see e.g. UniProt database accession no. P04626- 1) and thus human HER2 may, for example, be purified from a natural source or expressed using recombinant techniques for use in such methods. The amino acid and nucleic acid sequences of human HER2 are shown below in SEQ ID NO:s 43 and 44 respectively: SEQ ID NO:43 - Human HER2 amino acid sequence: 1 MKLRLPASPE THLDMLRHLY QGCQVVQGNL ELTYLPTNAS LSFLQDIQEV QGYVLIAHNQ 61 VRQVPLQRLR IVRGTQLFED NYALAVLDNG DPLNNTTPVT GASPGGLREL QLRSLTEILK 121 GGVLIQRNPQ LCYQDTILWK DIFHKNNQLA LTLIDTNRSR ACHPCSPMCK GSRCWGESSE 181 DCQSLTRTVC AGGCARCKGP LPTDCCHEQC AAGCTGPKHS DCLACLHFNH SGICELHCPA 241 LVTYNTDTFE SMPNPEGRYT FGASCVTACP YNYLSTDVGS CTLVCPLHNQ EVTAEDGTQR 301 CEKCSKPCAR VCYGLGMEHL REVRAVTSAN IQEFAGCKKI FGSLAFLPES FDGDPASNTA 361 PLQPEQLQVF ETLEEITGYL YISAWPDSLP DLSVFQNLQV IRGRILHNGA YSLTLQGLGI 421 SWLGLRSLRE LGSGLALIHH NTHLCFVHTV PWDQLFRNPH QALLHTANRP EDECVGEGLA 481 CHQLCARGHC WGPGPTQCVN CSQFLRGQEC VEECRVLQGL PREYVNARHC LPCHPECQPQ 541 NGSVTCFGPE ADQCVACAHY KDPPFCVARC PSGVKPDLSY MPIWKFPDEE GACQPCPINC 601 THSCVDLDDK GCPAEQRASP LTSIISAVVG ILLVVVLGVV FGILIKRRQQ KIRKYTMRRL 661 LQETELVEPL TPSGAMPNQA QMRILKETEL RKVKVLGSGA FGTVYKGIWI PDGENVKIPV 721 AIKVLRENTS PKANKEILDE AYVMAGVGSP YVSRLLGICL TSTVQLVTQL MPYGCLLDHV 781 RENRGRLGSQ DLLNWCMQIA KGMSYLEDVR LVHRDLAARN VLVKSPNHVK ITDFGLARLL 841 DIDETEYHAD GGKVPIKWMA LESILRRRFT HQSDVWSYGV TVWELMTFGA KPYDGIPARE 901 IPDLLEKGER LPQPPICTID VYMIMVKCWM IDSECRPRFR ELVSEFSRMA RDPQRFVVIQ 961 NEDLGPASPL DSTFYRSLLE DDDMGDLVDA EEYLVPQQGF FCPDPAPGAG GMVHHRHRSS 1021 STRSGGGDLT LGLEPSEEEA PRSPLAPSEG AGSDVFDGDL GMGAAKGLQS LPTHDPSPLQ 1081 RYSEDPTVPL PSETDGYVAP LTCSPQPEYV NQPDVRPQPP SPREGPLPAA RPAGATLERP 1141 KTLSPGKNGV VKDVFAFGGA VENPEYLTPQ GGAAPQPHPP PAFSPAFDNL YYWDQDPPER 1201 GAPPSTFKGT PTAENPEYLG LDVPV SEQ ID NO:44 - Human HER2 nucleic acid sequence: 1 gttctttatt ctactctccg ctgaagtcca cacagtttaa attaaagttc ccggattttt 61 gtgggcgcct gccccgcccc tcgtccccct gctgtgtcca tatatcgagg cgatagggtt 121 aagggaaggc ggacgcctga tgggttaatg agcaaactga agtgttttcc atgatctttt 181 ttgagtcgca attgaagtac cacctcccga gggtgattgc ttccccatgc ggggtagaac 241 ctttgctgtc ctgttcacca ctctacctcc agcacagaat ttggcttatg cctactcaat 301 gtgaagatga tgaggatgaa aacctttgtg atgatccact tccacttaat gaatggtggc 361 aaagcaaagc tatattcaag accacatgca aagctactcc ctgagcaaag agtcacagat 421 aaaacggggg caccagtaga atggccagga caaacgcagt gcagcacaga gactcagacc 481 ctggcagcca tgcctgcgca ggcagtgatg agagtgacat gtactgttgt ggacatgcac 541 aaaagtgagt gtgcaccggc acagacatga agctgcggct ccctgccagt cccgagaccc 601 acctggacat gctccgccac ctctaccagg gctgccaggt ggtgcaggga aacctggaac 661 tcacctacct gcccaccaat gccagcctgt ccttcctgca ggatatccag gaggtgcagg 721 gctacgtgct catcgctcac aaccaagtga ggcaggtccc actgcagagg ctgcggattg 781 tgcgaggcac ccagctcttt gaggacaact atgccctggc cgtgctagac aatggagacc 841 cgctgaacaa taccacccct gtcacagggg cctccccagg aggcctgcgg gagctgcagc 901 ttcgaagcct cacagagatc ttgaaaggag gggtcttgat ccagcggaac ccccagctct 961 gctaccagga cacgattttg tggaaggaca tcttccacaa gaacaaccag ctggctctca 1021 cactgataga caccaaccgc tctcgggcct gccacccctg ttctccgatg tgtaagggct 1081 cccgctgctg gggagagagt tctgaggatt gtcagagcct gacgcgcact gtctgtgccg 1141 gtggctgtgc ccgctgcaag gggccactgc ccactgactg ctgccatgag cagtgtgctg 1201 ccggctgcac gggccccaag cactctgact gcctggcctg cctccacttc aaccacagtg 1261 gcatctgtga gctgcactgc ccagccctgg tcacctacaa cacagacacg tttgagtcca 1321 tgcccaatcc cgagggccgg tatacattcg gcgccagctg tgtgactgcc tgtccctaca 1381 actacctttc tacggacgtg ggatcctgca ccctcgtctg ccccctgcac aaccaagagg 1441 tgacagcaga ggatggaaca cagcggtgtg agaagtgcag caagccctgt gcccgagtgt 1501 gctatggtct gggcatggag cacttgcgag aggtgagggc agttaccagt gccaatatcc 1561 aggagtttgc tggctgcaag aagatctttg ggagcctggc atttctgccg gagagctttg 1621 atggggaccc agcctccaac actgccccgc tccagccaga gcagctccaa gtgtttgaga 1681 ctctggaaga gatcacaggt tacctataca tctcagcatg gccggacagc ctgcctgacc 1741 tcagcgtctt ccagaacctg caagtaatcc ggggacgaat tctgcacaat ggcgcctact 1801 cgctgaccct gcaagggctg ggcatcagct ggctggggct gcgctcactg agggaactgg 1861 gcagtggact ggccctcatc caccataaca cccacctctg cttcgtgcac acggtgccct 1921 gggaccagct ctttcggaac ccgcaccaag ctctgctcca cactgccaac cggccagagg 1981 acgagtgtgt gggcgagggc ctggcctgcc accagctgtg cgcccgaggg cactgctggg 2041 gtccagggcc cacccagtgt gtcaactgca gccagttcct tcggggccag gagtgcgtgg 2101 aggaatgccg agtactgcag gggctcccca gggagtatgt gaatgccagg cactgtttgc 2161 cgtgccaccc tgagtgtcag ccccagaatg gctcagtgac ctgttttgga ccggaggctg 2221 accagtgtgt ggcctgtgcc cactataagg accctccctt ctgcgtggcc cgctgcccca 2281 gcggtgtgaa acctgacctc tcctacatgc ccatctggaa gtttccagat gaggagggcg 2341 catgccagcc ttgccccatc aactgcaccc actcctgtgt ggacctggat gacaagggct 2401 gccccgccga gcagagagcc agccctctga cgtccatcat ctctgcggtg gttggcattc 2461 tgctggtcgt ggtcttgggg gtggtctttg ggatcctcat caagcgacgg cagcagaaga 2521 tccggaagta cacgatgcgg agactgctgc aggaaacgga gctggtggag ccgctgacac 2581 ctagcggagc gatgcccaac caggcgcaga tgcggatcct gaaagagacg gagctgagga 2641 aggtgaaggt gcttggatct ggcgcttttg gcacagtcta caagggcatc tggatccctg 2701 atggggagaa tgtgaaaatt ccagtggcca tcaaagtgtt gagggaaaac acatccccca 2761 aagccaacaa agaaatctta gacgaagcat acgtgatggc tggtgtgggc tccccatatg 2821 tctcccgcct tctgggcatc tgcctgacat ccacggtgca gctggtgaca cagcttatgc 2881 cctatggctg cctcttagac catgtccggg aaaaccgcgg acgcctgggc tcccaggacc 2941 tgctgaactg gtgtatgcag attgccaagg ggatgagcta cctggaggat gtgcggctcg 3001 tacacaggga cttggccgct cggaacgtgc tggtcaagag tcccaaccat gtcaaaatta 3061 cagacttcgg gctggctcgg ctgctggaca ttgacgagac agagtaccat gcagatgggg 3121 gcaaggtgcc catcaagtgg atggcgctgg agtccattct ccgccggcgg ttcacccacc 3181 agagtgatgt gtggagttat ggtgtgactg tgtgggagct gatgactttt ggggccaaac 3241 cttacgatgg gatcccagcc cgggagatcc ctgacctgct ggaaaagggg gagcggctgc 3301 cccagccccc catctgcacc attgatgtct acatgatcat ggtcaaatgt tggatgattg 3361 actctgaatg tcggccaaga ttccgggagt tggtgtctga attctcccgc atggccaggg 3421 acccccagcg ctttgtggtc atccagaatg aggacttggg cccagccagt cccttggaca 3481 gcaccttcta ccgctcactg ctggaggacg atgacatggg ggacctggtg gatgctgagg 3541 agtatctggt accccagcag ggcttcttct gtccagaccc tgccccgggc gctgggggca 3601 tggtccacca caggcaccgc agctcatcta ccaggagtgg cggtggggac ctgacactag 3661 ggctggagcc ctctgaagag gaggccccca ggtctccact ggcaccctcc gaaggggctg 3721 gctccgatgt atttgatggt gacctgggaa tgggggcagc caaggggctg caaagcctcc 3781 ccacacatga ccccagccct ctacagcggt acagtgagga ccccacagta cccctgccct 3841 ctgagactga tggctacgtt gcccccctga cctgcagccc ccagcctgaa tatgtgaacc 3901 agccagatgt tcggccccag cccccttcgc cccgagaggg ccctctgcct gctgcccgac 3961 ctgctggtgc cactctggaa aggcccaaga ctctctcccc agggaagaat ggggtcgtca 4021 aagacgtttt tgcctttggg ggtgccgtgg agaaccccga gtacttgaca ccccagggag 4081 gagctgcccc tcagccccac cctcctcctg ccttcagccc agccttcgac aacctctatt 4141 actgggacca ggacccacca gagcgggggg ctccacccag caccttcaaa gggacaccta 4201 cggcagagaa cccagagtac ctgggtctgg acgtgccagt gtgaaccaga aggccaagtc 4261 cgcagaagcc ctgatgtgtc ctcagggagc agggaaggcc tgacttctgc tggcatcaag 4321 aggtgggagg gccctccgac cacttccagg ggaacctgcc atgccaggaa cctgtcctaa 4381 ggaaccttcc ttcctgcttg agttcccaga tggctggaag gggtccagcc tcgttggaag 4441 aggaacagca ctggggagtc tttgtggatt ctgaggccct gcccaatgag actctagggt 4501 ccagtggatg ccacagccca gcttggccct ttccttccag atcctgggta ctgaaagcct 4561 tagggaagct ggcctgagag gggaagcggc cctaagggag tgtctaagaa caaaagcgac 4621 ccattcagag actgtccctg aaacctagta ctgcccccca tgaggaagga acagcaatgg 4681 tgtcagtatc caggctttgt acagagtgct tttctgttta gtttttactt tttttgtttt 4741 gtttttttaa agatgaaata aagacccagg gggagaatgg gtgttgtatg gggaggcaag 4801 tgtggggggt ccttctccac acccactttg tccatttgca aatatatttt ggaaaaca Hybridomas that produce suitable antibodies may be grown in vitro or in vivo using known procedures. Monoclonal antibodies may be isolated from the culture media or body fluids, by conventional immunoglobulin purification procedures such as ammonium sulfate precipitation, gel electrophoresis, dialysis, chromatography, and ultrafiltration, if desired. Undesired activity if present, can be removed, for example, by running the preparation over adsorbents made of the immunogen attached to a solid phase and eluting or releasing the desired antibodies off the immunogen. If desired, the antibody (monoclonal or polyclonal) of interest may be sequenced and the polynucleotide sequence may then be cloned into a vector for expression or propagation. The sequence encoding the antibody may be maintained in a vector in a host cell and the host cell can then be expanded and frozen for future use. Phage display technology, for instance as described in US 5,565,332 and other published documents, may be used to select and produce human antibodies and antibody fragments in vitro, from immunoglobulin variable (V) domain gene repertoires from unimmunized donors (e.g. from human subjects, including patients suffering from a relevant disorder). For example, existing antibody phage display libraries may be panned in parallel against a large collection of synthetic polypeptides. According to this technique, antibody V domain genes are cloned in frame into either a major or minor coat protein gene of a filamentous bacteriophage, such as M13 or fd, and displayed as functional antibody fragments on the surface of the phage particle. Because the filamentous particle contains a single-stranded DNA copy of the phage genome, selections based on the functional properties of the antibody also result in selection of the gene encoding the antibody exhibiting those properties. Thus antibody sequences selected using phage display from human libraries may include human CDR or variable region sequences conferring specific binding to a specific antigen such as HER2, which may be used to provide fully human antibodies for use in the present invention. Methods for deriving heavy and light chain sequences from human B cell and plasma cell clones are also well known in the art and typically performed using polymerase chain reaction (PCR) techniques, examples of the methods are described in: Kuppers R, Methods Mol Biol. 2004;271:225-38; Yoshioka M et al., BMC Biotechnol.2011 Jul 21;11:75; Scheeren FA et al., PLoS ONE 2011, 6(4): e17189. doi:10.1371 / journal.pone.0017189; Wrammert J et al., Nature 2008453, 667-671; Kurosawa N et al., BMC Biotechnol. 2011 Apr 13;11:39; Tiller et al., J Immunol Methods. 2008 January 1; 329(1-2): 112-124. Thus antibody sequences selected using B cell clones may include human CDR or variable region sequences conferring specific binding to e.g. HER2, which may be used to provide fully human antibodies for use in the present invention. IgE antibodies The therapeutic antibody to be administered to the subject may be an IgE antibody, i.e. an antibody of the isotype IgE. There are some fundamental structural differences between IgEs and IgGs, and these have functional effects. While IgE shares the same basic molecular architecture as antibodies of other classes, the heavy chain of IgE contains one more domain than the heavy chain of IgG. The Cε3 and Cε4 domains of IgE are homologous in sequence, and similar in structure, to the Cγ2 and Cγ3 domains of IgG, so that it is the Cε2 domains that are the most obvious distinguishing feature of IgE. The Cε2 domain has been found to be folded back against the heavy chain IgE and to make extensive contact with the Cε3 domain. This bent structure of the IgE heavy chain allows it to adopt an open or closed conformation. The unbound IgE dimer has one chain in the open and one chain in the closed conformation. Binding of FcεRI to IgE is biphasic and is thought to involve initial binding to the open Cε chain followed by extensive structural rearrangement to allow binding to the closed Cε chain. The binding between the IgE dimer and the FcεRI occurs with 1:1 stoichiometry despite the presence of two identical Cε-chains. This rearrangement results in a very tight interaction between IgE and FcεRI, and a much greater affinity of IgE for its Fc receptor than found with IgG and FcγRs (McDonnell, J. M., R. Calvert, et al. (2001) Nat Struct Biol 8(5): 437-441). The antibodies used in the present invention are typically capable of binding to Fcɛ receptors, e.g. to the FcɛRI and / or the FcɛRII receptors. Preferably the antibody is at least capable of binding to FcɛRI (i.e. the high affinity Fcɛ receptor) or is at least capable of binding to FcɛRII (CD23, the low affinity Fcɛ receptor). Typically the antibodies are also capable of activating Fcɛ receptors, e.g. expressed on cells of the immune system, in order to initiate effector functions mediated by IgE. The epsilon (ɛ) heavy chain is definitive for IgE antibodies, and comprises an N-terminal variable domain VH, and four constant domains Cɛ1 -Cɛ4. As with other antibody isotypes, the variable domains confer antigen specificity and the constant domains recruit the isotype- specific effector functions. IgE differs from the more abundant IgG isotypes, in that it is unable to fix complement and does not bind to the Fc receptors FcγRI, RII and RIII expressed on the surfaces of mononuclear cells, NK cells and neutrophils. However, IgE is capable of very specific interactions with the “high affinity” IgE receptor on a variety of immune cells such as mast cells, basophils, monocytes / macrophages, eosinophils (FcɛRI, Ka. 1011 M-1), and with the “low affinity” receptor, Fcɛ RII (Ka.107 M-¹), also known as CD23, expressed on inflammatory and antigen presenting cells (e.g. monocytes / macrophages, platelets, dendritic cells, T and B lymphocytes. The sites on IgE responsible for these receptor interactions have been mapped to peptide sequences on the Cɛ chain, and are distinct. The FcɛRI site lies in a cleft created by residues between Gln 301 and Arg 376, and includes the junction between the Cɛ2 and Cɛ3 domains (Helm, B. et al. (1988) Nature 331, 180183). The FcɛRII binding site is located within Cɛ3 around residue Val 370 (Vercelli, D. et al. (1989) Nature 338, 649-651). A major difference distinguishing the two receptors is that FcɛRI binds monomeric Cɛ, whereas FcɛRII will only bind dimerised Cɛ, i.e. the two Cɛ chains must be associated. Although IgE is glycosylated in vivo, this is not necessary for its binding to FcɛRI and FcɛRRII. Binding is in fact marginally stronger in the absence of glycosylation (Vercelli, D. et al. (1989) et. Supra). Thus binding to Fcɛ receptors and related effector functions are typically mediated by the heavy chain constant domains of the antibody, in particular by domains which together form the Fc region of the antibody. The antibodies described herein typically comprise at least a portion of an IgE antibody e.g. one or more constant domains derived from an IgE, preferably a human IgE. In particular embodiments, the antibodies comprise one or more domains (derived from IgE) selected from Cɛl, Cɛ2, Cɛ3 and Cɛ4. In one embodiment, the antibody comprises at least Cɛ2 and Cɛ3, more preferably at least Cɛ2, Cɛ3 and Cɛ4, preferably wherein the domains are derived from a human IgE. In one embodiment, the antibody comprises an epsilon (ɛ) heavy chain, preferably a human ɛ heavy chain. The amino acid sequences of constant domains derived from human IgE are shown in e.g. Table 1 (SEQ ID NO:s 41 and 42, non-bold text in SEQ ID Nos: 1 and 6). Nucleotide sequences encoding constant domains derived from human IgE, in particular Cɛ1, Cɛ2, Cɛ3 and Cɛ4 domains, are also disclosed in e.g. WO 2013 / 050725. The amino acid sequences of other human and mammalian IgEs and domains thereof, including human Cɛl, Cɛ2, Cɛ3 and Cɛ4 domains and human ɛ heavy chain sequences, are known in the art and are available from public-accessible databases. For instance, databases of human immunoglobulin sequences are accessible from the International ImMunoGeneTics Information System (IMGT®) website at http: / / www.imgt.org. As one example, the sequences of various human IgE heavy (ɛ) chain alleles and their individual constant domains (Cɛ1-4) are accessible at http: / / www.imgt.org / IMGT_GENE-DB / GENElect?query=2+IGHE&species=Homo+sapiens. Preferred anti-HER2 IgE antibodies and variants / fragments thereof In one embodiment, the anti-HER2 antibody comprises a VH domain comprising at least a portion of the amino acid sequence as defined in any one of SEQ ID NOs: 2, 12, 22 or 32, e.g. comprising at least 20, 30, 50 or 100 amino acids of any one of SEQ ID NOs: 2, 12, 22 or 32 or the full length of any one of SEQ ID NOs: 2, 12, 22 or 32 or one, two or three CDRs present in any one of SEQ ID NOs: 2, 12, 22 or 32 (e.g. defined according to Kabat, Chothia or IMGT). In one embodiment, the anti-HER2 antibody comprises a VL domain comprising at least a portion of the amino acid sequence as defined in any one of SEQ ID NOs: 7, 17, 27 or 37, e.g. comprising at least 20, 30, 50 or 100 amino acids of any one of SEQ ID NOs: 7, 17, 27 or 37 or the full length of any one of SEQ ID NOs: 7, 17, 27 or 37 or one, two or three CDRs present in any one of SEQ ID NOs: 7, 17, 27 or 37 (e.g. defined according to Kabat, Chothia or IMGT). In general, functional fragments of the sequences defined above may be used in the present invention. Functional fragments may be of any length as specified above (e.g. at least 50, 100, 300 or 500 nucleotides, or at least 50, 100, 200 or 300 amino acids), provided that the fragment retains the required activity when present in the antibody (e.g. specific binding to HER2 and / or a Fcɛ receptor). Variants of the above amino acid and nucleotide sequences may also be used in the present invention, provided that the resulting antibody binds an Fcɛ receptor. Typically such variants have a high degree of sequence identity with one of the sequences specified above. The similarity between amino acid or nucleotide sequences is expressed in terms of the similarity between the sequences, otherwise referred to as sequence identity. Sequence identity is frequently measured in terms of percentage identity (or similarity or homology); the higher the percentage, the more similar the two sequences are. Homologs or variants of the amino acid or nucleotide sequence will possess a relatively high degree of sequence identity when aligned using standard methods. Methods of alignment of sequences for comparison are well known in the art. Various programs and alignment algorithms are described in: Smith and Waterman, Adv. Appl. Math. 2:482, 1981; Needleman and Wunsch, J. Mol. Biol. 48:443, 1970; Pearson and Lipman, Proc. Natl. Acad. Sci. U.S.A.85:2444, 1988; Higgins and Sharp, Gene 73:237, 1988; Higgins and Sharp, CABIOS 5:151, 1989; Corpet et al., Nucleic Acids Research 16:10881, 1988; and Pearson and Lipman, Proc. Natl. Acad. Sci. U.S.A. 85:2444, 1988. Altschul et al., Nature Genet. 6:119, 1994, presents a detailed consideration of sequence alignment methods and homology calculations. The NCBI Basic Local Alignment Search Tool (BLAST) (Altschul et al., J. Mol. Biol.215:403, 1990) is available from several sources, including the National Center for Biotechnology Information (NCBI, Bethesda, Md.) and on the internet, for use in connection with the sequence analysis programs blastp, blastn, blastx, tblastn and tblastx. A description of how to determine sequence identity using this program is available on the NCBI website on the internet. Homologs and variants of the antibody (e.g. anti-HER2 antibody or a domain thereof, e.g. a VL, VH, CL or CH domain) typically have at least about 75%, for example at least about 80%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with the original sequence (e.g. a sequence defined above), for example counted over the full length alignment with the amino acid sequence of the antibody or domain thereof using the NCBI Blast 2.0, gapped blastp set to default parameters. For comparisons of amino acid sequences of greater than about 30 amino acids, the Blast 2 sequences function is employed using the default BLOSUM62 matrix set to default parameters, (gap existence cost of 11, and a per residue gap cost of 1). When aligning short peptides (fewer than around 30 amino acids), the alignment should be performed using the Blast 2 sequences function, employing the PAM30 matrix set to default parameters (open gap 9, extension gap 1 penalties). Proteins with even greater similarity to the reference sequences will show increasing percentage identities when assessed by this method, such as at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity. When less than the entire sequence is being compared for sequence identity, homologs and variants will typically possess at least 80% sequence identity over short windows of 10-20 amino acids, and may possess sequence identities of at least 85% or at least 90% or 95% depending on their similarity to the reference sequence. Methods for determining sequence identity over such short windows are available at the NCBI website on the internet. One of skill in the art will appreciate that these sequence identity ranges are provided for guidance only; it is entirely possible that strongly significant homologs could be obtained that fall outside of the ranges provided. Typically variants may contain one or more conservative amino acid substitutions compared to the original amino acid or nucleic acid sequence. Conservative substitutions are those substitutions that do not substantially affect or decrease the affinity of an antibody to the target antigen (e.g. HER2 ^ and / or Fcɛ receptors. For example, a human antibody that specifically binds HER2 may include up to 1, up to 2, up to 5, up to 10, or up to 15 conservative substitutions compared to the original sequence (e.g. as defined above) and retain specific binding to the HER2 polypeptide. The term conservative variation also includes the use of a substituted amino acid in place of an unsubstituted parent amino acid, provided that antibody specifically binds the target antigen (e.g. HER2 ^. Non-conservative substitutions are those that reduce an activity or binding to the target antigen (e.g. HER2 ^ ^and / or Fcɛ receptors. Functionally similar amino acids which may be exchanged by way of conservative substitution are well known to one of ordinary skill in the art. The following six groups are examples of amino acids that are considered to be conservative substitutions for one another: 1) Alanine (A), Serine (S), Threonine (T); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W). In preferred embodiments, the IgE antibody lacks a cytotoxic moiety and / or is administered as a monotherapy. It has surprisingly been found that anti-HER2 IgE antibodies are capable of targeting low HER2-expressing tumors without requiring administration of a cytotoxic drug (either in the form of an ADC or in a chemotherapeutic combination). This can avoid the disadvantages of ADCs and in particular may lead to reduced toxicity, improved tolerability and an improved safety profile. Thus the antibody may comprise, consist of or consist essentially of (optionally glycosylated) polypeptide chains. For instance the antibody may comprise, consist of or consist essentially of one or more (preferably four) polypeptide chains, e.g. two immunoglobulin heavy chains and optionally two immunoglobulin light chains. Preferably the heavy and / or light chains comprises one or more domains from an IgE antibody. In particular, it is preferred that the antibody is not an antibody-drug conjugate (ADC). Thus the antibody may lack a further drug or group having a cytotoxic effect, e.g. a chemotherapeutic or drug that is capable of (directly) killing cancer cells. The antibody may further lack a linker or other group for conjugating a cytotoxic moiety to a polypeptide. Further IgE antibodies As described above, in preferred embodiments the IgE antibody binds to HER2. Preferably the IgE antibodies are capable of inducing cytotoxicity (e.g. ADCC) and / or phagocytosis (ADCP), particularly against cancer cells expressing such an antigen. In some embodiments, one or more of the variable domains and / or one or more of the CDRs, preferably at least three CDRs, or more preferably all six CDRs may be derived from one or more of the following antibodies: trastuzumab, pertuzumab or margetuximab (see e.g. Ling et al., Front Immunol.2018; 9: 469; Rugo et al., JAMA Oncology.2021;7(4):573–584). In another embodiment, the antibody is a chimaeric, humanized or fully human antibody that specifically binds the epitope bound by one of the above antibodies. The IgE antibody may further comprise one or more IgE constant domains, e.g. Cɛ1-Cɛ4 domains, as described above. Production of antibodies and nucleic acids Nucleic acid molecules (also referred to as polynucleotides) encoding the polypeptides provided herein (including, but not limited to antibodies and functional fragments thereof) can readily be produced by one of skill in the art, using the amino acid sequences provided herein, sequences available in the art, and the genetic code. In addition, one of skill can readily construct a variety of clones containing functionally equivalent nucleic acids, such as nucleic acids which differ in sequence but which encode the same effector molecule or antibody sequence. Thus, nucleic acids encoding antibodies are provided herein. Nucleic acid sequences encoding the antibodies that specifically bind the target antigen (e.g. HER2 ^, or functional fragments thereof, can be prepared by any suitable method including, for example, cloning of appropriate sequences or by direct chemical synthesis by methods such as the phosphotriester method of Narang et al., Meth. Enzymol. 68:90-99, 1979; the phosphodiester method of Brown et al., Meth. Enzymol. 68:109-151, 1979; the diethylphosphoramidite method of Beaucage et al., Tetra. Lett.22:1859-1862, 1981; the solid phase phosphoramidite triester method described by Beaucage & Caruthers, Tetra. Letts. 22(20):1859-1862, 1981, for example, using an automated synthesizer as described in, for example, Needham-VanDevanter et al., Nucl. Acids Res.12:6159-6168, 1984; and, the solid support method of U.S. Pat. No. 4,458,066. Chemical synthesis produces a single stranded oligonucleotide. This can be converted into double stranded DNA by hybridization with a complementary sequence or by polymerization with a DNA polymerase using the single strand as a template. One of skill would recognize that while chemical synthesis of DNA is generally limited to sequences of about 100 bases, longer sequences may be obtained by the ligation of shorter sequences. Exemplary nucleic acids encoding antibodies, or functional fragments thereof, can be prepared by cloning techniques. Examples of appropriate cloning and sequencing techniques, and instructions sufficient to direct persons of skill through many cloning exercises are found see, for example, Molecular Cloning: A Laboratory Manual, 2nd ed., vol.1-3, ed. Sambrook et al., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989); and Current Protocols in Molecular Biology (Ausubel et al., eds 1995 supplement)). Product information from manufacturers of biological reagents and experimental equipment also provide useful information. Such manufacturers include the SIGMA Chemical Company (Saint Louis, Mo.), R&D Systems (Minneapolis, Minn.), Pharmacia Amersham (Piscataway, N.J.), CLONTECH Laboratories, Inc. (Palo Alto, Calif.), Chem Genes Corp., Aldrich Chemical Company (Milwaukee, Wis.), Glen Research, Inc., GIBCO BRL Life Technologies, Inc. (Gaithersburg, Md.), Fluka Chemica-Biochemika Analytika (Fluka Chemie AG, Buchs, Switzerland), Invitrogen (Carlsbad, Calif.), and Applied Biosystems (Foster City, Calif.), as well as many other commercial sources known to one of skill. Nucleic acids encoding native antibodies can be modified to form the antibodies described herein. Modification by site-directed mutagenesis is well known in the art. Nucleic acids can also be prepared by amplification methods. Amplification methods include polymerase chain reaction (PCR), the ligase chain reaction (LCR), the transcription-based amplification system (TAS), the self-sustained sequence replication system (3SR). A wide variety of cloning methods, host cells, and in vitro amplification methodologies are well known to persons of skill. In one embodiment, antibodies are prepared by inserting a cDNA which encodes one or more antibody domains (e.g. a mouse IgG1 heavy chain variable region which binds human HER2) into a vector which comprises a cDNA encoding one or more further antibody domains (e.g. a human heavy chain ɛ constant region). The insertion is made so that the antibody domains are read in frame that is in one continuous polypeptide which contains a functional antibody region. In one embodiment, cDNA encoding a heavy chain constant region is ligated to a heavy chain variable region so that the constant region is located at the carboxyl terminus of the antibody. The heavy chain-variable and / or constant regions can subsequently be ligated to a light chain variable and / or constant region of the antibody using disulfide bonds. Once the nucleic acids encoding the antibody or functional fragment thereof have been isolated and cloned, the desired protein can be expressed in a recombinantly engineered cell such as bacteria, plant, yeast, insect and mammalian cells. It is expected that those of skill in the art are knowledgeable in the numerous expression systems available for expression of proteins including E. coli, other bacterial hosts, yeast, and various higher eukaryotic cells such as the COS, CHO, HeLa and myeloma cell lines. One or more DNA sequences encoding the antibody or fragment thereof can be expressed in vitro by DNA transfer into a suitable host cell. The cell may be prokaryotic or eukaryotic. The term also includes any progeny of the subject host cell. It is understood that all progeny may not be identical to the parental cell since there may be mutations that occur during replication. Methods of stable transfer, meaning that the foreign DNA is continuously maintained in the host, are known in the art. Hybridomas expressing the antibodies of interest are also encompassed by this disclosure. The expression of nucleic acids encoding the isolated antibodies and antibody fragments described herein can be achieved by operably linking the DNA or cDNA to a promoter (which is either constitutive or inducible), followed by incorporation into an expression cassette. The cassettes can be suitable for replication and integration in either prokaryotes or eukaryotes. Typical expression cassettes contain specific sequences useful for regulation of the expression of the DNA encoding the protein. For example, the expression cassettes can include appropriate promoters, enhancers, transcription and translation terminators, initiation sequences, a start codon (i.e., ATG) in front of a protein-encoding gene, splicing signal for introns, maintenance of the correct reading frame of that gene to permit proper translation of mRNA, and stop codons. To obtain high level expression of a cloned gene, it is desirable to construct expression cassettes which contain, at the minimum, a strong promoter to direct transcription, a ribosome binding site for translational initiation, and a transcription / translation terminator. For E. coli, this includes a promoter such as the T7, trp, lac, or lambda promoters, a ribosome binding site, and preferably a transcription termination signal. For eukaryotic cells, the control sequences can include a promoter and / or an enhancer derived from, for example, an immunoglobulin gene, SV40 or cytomegalovirus, and a polyadenylation sequence, and can further include splice donor and acceptor sequences. The cassettes can be transferred into the chosen host cell by well-known methods such as transformation or electroporation for E. coli and calcium phosphate treatment, electroporation or lipofection for mammalian cells. Cells transformed by the cassettes can be selected by resistance to antibiotics conferred by genes contained in the cassettes, such as the amp, gpt, neo and hyg genes. When the host is a eukaryote, such methods of transfection of DNA as calcium phosphate coprecipitates, conventional mechanical procedures such as microinjection, electroporation, insertion of a plasmid encased in liposomes, or virus vectors may be used. Eukaryotic cells can also be co-transformed with polynucleotide sequences encoding the antibody, labelled antibody, or functional fragment thereof, and a second foreign DNA molecule encoding a selectable phenotype, such as the herpes simplex thymidine kinase gene. Another method is to use a eukaryotic viral vector, such as simian virus 40 (SV40) or bovine papilloma virus, to transiently infect or transform eukaryotic cells and express the protein (see for example, Eukaryotic Viral Vectors, Cold Spring Harbor Laboratory, Gluzman ed., 1982). One of skill in the art can readily use an expression systems such as plasmids and vectors of use in producing proteins in cells including higher eukaryotic cells such as the COS, CHO, HeLa and myeloma cell lines. Modifications can be made to a nucleic acid encoding a polypeptide described herein (e.g., a human HER2-specific IgE antibody) without diminishing its biological activity. Some modifications can be made to facilitate the cloning, expression, or incorporation of the targeting molecule into a fusion protein. Such modifications are well known to those of skill in the art and include, for example, termination codons, a methionine added at the amino terminus to provide an initiation, site, additional amino acids placed on either terminus to create conveniently located restriction sites, or additional amino acids (such as poly His) to aid in purification steps. In addition to recombinant methods, the antibodies of the present disclosure can also be constructed in whole or in part using standard peptide synthesis well known in the art. Once expressed, the recombinant antibodies can be purified according to standard procedures of the art, including ammonium sulfate precipitation, affinity columns, column chromatography, and the like (see, generally, R. Scopes, PROTEIN PURIFICATION, Springer-Verlag, N.Y., 1982). The antibodies, immunoconjugates and effector molecules need not be 100% pure. Once purified, partially or to homogeneity as desired, if to be used therapeutically, the polypeptides should be substantially free of endotoxin. Often, functional heterologous proteins from E. coli or other bacteria are isolated from inclusion bodies and require solubilization using strong denaturants, and subsequent refolding. During the solubilization step, as is well known in the art, a reducing agent must be present to separate disulfide bonds. An exemplary buffer with a reducing agent is: 0.1 M Tris pH 8, 6 M guanidine, 2 mM EDTA, 0.3 M DTE (dithioerythritol). Reoxidation of the disulfide bonds can occur in the presence of low molecular weight thiol reagents in reduced and oxidized form, as described in Saxena et al., Biochemistry 9: 5015-5021, 1970, and especially as described by Buchner et al., supra. Renaturation is typically accomplished by dilution (for example, 100-fold) of the denatured and reduced protein into refolding buffer. An exemplary buffer is 0.1 M Tris, pH 8.0, 0.5 M L- arginine, 8 mM oxidized glutathione (GSSG), and 2 mM EDTA. As a modification to the two chain antibody purification protocol, the heavy and light chain regions are separately solubilized and reduced and then combined in the refolding solution. An exemplary yield is obtained when these two proteins are mixed in a molar ratio such that a 5 fold molar excess of one protein over the other is not exceeded. Excess oxidized glutathione or other oxidizing low molecular weight compounds can be added to the refolding solution after the redox-shuffling is completed. In addition to recombinant methods, the antibodies, labelled antibodies and functional fragments thereof that are disclosed herein can also be constructed in whole or in part using standard peptide synthesis. Solid phase synthesis of the polypeptides of less than about 50 amino acids in length can be accomplished by attaching the C-terminal amino acid of the sequence to an insoluble support followed by sequential addition of the remaining amino acids in the sequence. Techniques for solid phase synthesis are described by Barany & Merrifield, The Peptides: Analysis, Synthesis, Biology. Vol.2: Special Methods in Peptide Synthesis, Part A. pp.3-284; Merrifield et al., J. Am. Chem. Soc.85:2149-2156, 1963, and Stewart et al., Solid Phase Peptide Synthesis, 2nd ed., Pierce Chem. Co., Rockford, Ill., 1984. Proteins of greater length may be synthesized by condensation of the amino and carboxyl termini of shorter fragments. Methods of forming peptide bonds by activation of a carboxyl terminal end (such as by the use of the coupling reagent N,N’-dicylohexylcarbodimide) are well known in the art. In one embodiment, the antibodies, nucleic acids, expression vectors, host cells or other biological products are isolated. By “isolated” it is meant that the product has been substantially separated or purified away from other biological components in the environment (such as a cell) in which the component naturally occurs, i.e., other chromosomal and extra-chromosomal DNA and RNA, proteins and organelles. Nucleic acids and antibodies that have been “isolated” include nucleic acids and antibodies purified by standard purification methods. The term also embraces nucleic acids and antibodies prepared by recombinant expression in a host cell as well as chemically synthesized nucleic acids. Compositions and therapeutic methods Compositions are provided herein that include a carrier and one or more therapeutic IgE antibodies, or functional fragments thereof. The compositions can be prepared in unit dosage forms for administration to a subject. The antibody can be formulated for systemic or local (such as intra-tumour) administration. In one example, the therapeutic IgE antibody is formulated for parenteral administration, such as intravenous administration or subcutaneous administration. The compositions for administration can include a solution of the antibody (or a functional fragment thereof) dissolved in a pharmaceutically acceptable carrier, such as an aqueous carrier. A variety of aqueous carriers can be used, for example, buffered saline and the like. These solutions are sterile and generally free of undesirable matter. These compositions may be sterilized by conventional, well known sterilization techniques. The compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents and the like, for example, sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate and the like. The concentration of the antibody and excipients in these formulations can vary, and will be selected primarily based on fluid volumes, viscosities, body weight and the like in accordance with the particular mode of administration selected and the subject’s needs. Actual methods for preparing administrable compositions will be known or apparent to those skilled in the art and are described in more detail in such publications as Remington’s Pharmaceutical Science, 19th ed., Mack Publishing Company, Easton, Pa. (1995). In preferred embodiments the compositions are provided as unit dosage forms, e.g. comprising a defined amount of the IgE antibody suitable for administration to a subject in a single dose. The unit dosage forms may be packaged individually, e.g. in single containers, vials, pre-filled syringes or the like. The unit dosage forms may be suitable for immediate administration to the subject (e.g. may comprise a physiologically acceptable concentration of salts) or the unit dosage forms may be provided in concentrated or lyophilized form (e.g. for dilution with sterile saline solution before use). The anti-HER2 IgE antibody may be administered at any suitable dose. In preferred embodiments described herein, a typical unit dose of the pharmaceutical composition (e.g. for intravenous administration) comprises less than 50 mg of the IgE antibody. For instance, the composition (i.e. in unit dosage form) may comprise less than 40mg, 30 mg, 25 mg, 20 mg, 15 mg, 10 mg, 5 mg, 3 mg, or 1 mg of the IgE antibody. The composition may comprise at least 10 µg, 100 µg, 200 µg, 300 µg, 500 µg, 700 µg, 1 mg, 3 mg, 5 mg or 10 mg of the IgE antibody. In preferred embodiments, the composition comprises comprising 10 µg to 50 mg, 70 µg to 30 mg, 300 µg to 50 mg, 300 µg to 30 mg, 300 µg to 3 mg, 500 µg to 50 mg, 500 µg to 30 mg, 500 µg to 10 mg, 500 µg to 3 mg, 700 µg to 50 mg, 700 µg to 30 mg, 700 µg to 10 mg, 700 µg to 3 mg, 500 µg to 5 mg, 500 µg to 1 mg, or about 700 µg of the IgE antibody. In some embodiments, the composition may comprise an amount of the IgE antibody within one or more of the above ranges, but excluding one or more of the following amounts: 1µg, 5µg, 10µg, 50µg, 100µg, 500µg, 1mg, 2mg, 4mg, 5mg, 10mg or 15mg. For instance, the composition may comprise 2 µg to 9 µg, 11 µg to 99 µg, 101 µg to 499 µg, 501 to 999 µg or 2 mg to 9 mg. The dosage of the IgE antibody administered to the subject may be based on the subject’s body weight. Thus the dose of the IgE antibody administered to the subject may be e.g. less than 1 mg / kg. Preferably the IgE antibody may be administered to the subject in a dose (per administration) of e.g. less than 0.7 mg / kg, 0.5 mg / kg, 0.3 mg / kg, 0.1 mg / kg, 0.07 mg / kg, 0.05 mg / kg, 0.03 mg / kg or 0.01 mg / kg. The dose of the IgE antibody administered to the subject may be at least 0.001 mg / kg, 0.003 mg / kg, 0.005 mg / kg, 0.007 mg / kg, 0.01 mg / kg, 0.05 mg / kg or 0.1 mg / kg. In preferred embodiments, the dose of the IgE antibody administered to the subject may be 0.001-1 mg / kg, 0.003-0.7 mg / kg, 0.005-0.5 mg / kg, 0.005-0.1 mg / kg, 0.005- 0.05 mg / kg, 0.007-0.03 mg / kg or 0.007-0.15 mg / kg. In some embodiments, the dose of the IgE antibody administered to the subject may be within one or more of the above defined ranges, but excluding one or more of the following dosages: 1µg / kg, 10µg / kg, 100µg / kg or 0.5 mg / kg. For instance, the dose of the IgE antibody may be 2 to 9 µg / kg, 11 to 99 µg / kg, 101 to 499 µg / kg or 0.51 to 0.7 mg / kg. In embodiments of the present invention, the unit dosages of the IgE antibody described above are at administered at most once a week, e.g. the maximum weekly dose of the IgE antibody is 50 mg, 40mg, 30 mg, 25 mg, 20 mg, 15 mg, 10 mg, 5 mg, 3 mg, or 1 mg. For instance the weekly dose of the IgE antibody may be 10 µg to 50 mg, 70 µg to 30 mg, 300 µg to 50 mg, 300 µg to 30 mg, 300 µg to 3 mg, 500 µg to 50 mg, 500 µg to 30 mg, 500 µg to 10 mg, 500 µg to 3 mg, 700 µg to 50 mg, 700 µg to 30 mg, 700 µg to 10 mg, 700 µg to 3 mg, 500 µg to 5 mg, 500 µg to 1 mg, or about 700 µg. The weekly dose of the IgE antibody may also be determined according to the subject’s body weight, e.g. the IgE antibody may be administered to the subject in a dose of e.g. less than 0.7 mg / kg / week, 0.5 mg / kg / week, 0.3 mg / kg / week, 0.1 mg / kg / week, 0.07 mg / kg / week, 0.05 mg / kg / week, 0.03 mg / kg / week or 0.01 mg / kg / week. In preferred embodiments, the dose of the IgE antibody administered to the subject may be 0.001-1 mg / kg / week, 0.003-0.7 mg / kg / week, 0.005-0.5 mg / kg / week, 0.005-0.1 mg / kg / week, 0.005- 0.05 mg / kg / week, 0.007-0.03 mg / kg / week or 0.007-0.15 mg / kg / week. In some embodiments, the dose of the IgE antibody administered to the subject may be within one or more of the above defined ranges, but excluding one or more of the following dosages: 1µg / kg / day (7µg / kg / week), 10µg / kg / day (70µg / kg / week) or 100µg / kg / day (0.7 mg / kg / week). For instance, the dose of the IgE antibody may be 2 to 6 µg / kg / week, 8 to 69 µg / kg / week, or 71 to 699 µg / kg / week. In one embodiment, the pharmaceutical composition is a liquid comprising one or more excipients selected from sodium citrate, L-arginine, sucrose, polysorbate 20 and / or sodium chloride. Preferably the composition has a pH of 6.0 to 8.0, e.g. about 6.5. Preferred concentrations of the excipients include: 0.05 to 0.5 M (e.g. about 0.1 M) sodium citrate; 10 to 50 g / L (e.g. about 30 g / L) L-arginine; 10 to 100 g / L (e.g. about 50 g / L) sucrose; 0.01 to 0.05% w / w (e.g.0.02% w / w) polysorbate 20. In one embodiment, the IgE antibody is present in such a formulation at a concentration of about 0.1 mg / ml to 10 mg / ml or 0.5 mg / ml to 2 mg / ml, e.g. about 1 mg / ml. In some embodiments, such a composition may be formulated as a unit dosage form e.g. in a volume of about 1 ml of solution comprising about 1 mg of the IgE antibody, for instance in a 2 ml type I glass vial. The composition may be diluted with sterile saline (0.9% w / v) before administration to the subject, e.g. in an amount of 1 ml of the composition in 250 ml of saline. Antibodies may be provided in lyophilized form and rehydrated with sterile water before administration, although they are also provided in sterile solutions of known concentration. The antibody solution is then added to an infusion bag containing 0.9% sodium chloride, USP, and administered to the subject. Considerable experience is available in the art in the administration of antibody drugs, which have been marketed in the U.S. since the approval of RITUXAN (Registered trademark) in 1997. Antibodies can be administered by slow infusion, rather than in an intravenous push or bolus. In one example, a higher loading dose is administered, with subsequent, maintenance doses being administered at a lower level. For example, an initial loading dose may be infused over a period of some 90 minutes, followed by weekly maintenance doses for 4-8 weeks infused over a 30 minute period if the previous dose was well tolerated. The antibody (or functional fragment thereof) can be administered to slow or inhibit the growth of cells, such as cancer cells. In these applications, a therapeutically effective amount of an antibody is administered to a subject in an amount sufficient to inhibit growth, replication or metastasis of cancer cells, or to inhibit a sign or a symptom of the cancer. In some embodiments, the antibodies are administered to a subject to inhibit or prevent the development of metastasis, or to decrease the size or number of metasases, such as micrometastases, for example micrometastases to the regional lymph nodes (Goto et al., Clin. Cancer Res. 14(11):3401-3407, 2008). Thus in some embodiments, the IgE antibody is used to treat cancer and / or to delay or prevent the progression of cancer. By “delay or prevent the progression” of cancer it is meant that, for example, the cancer is at least stable for a period of time after administration of the antibody, e.g. for at least 6 weeks, at least 12 weeks, at least 6 months or at least 12 months. “Stable” disease may be defined e.g. as a change in the RECIST score of less than 20%. RECIST (Response Evaluation Criteria in Solid Tumours) evaluation is a simple method for determining whether a patient’s disease has improved, stayed about the same, or worsened following treatment with a cancer therapeutic, and is commonly used in clinical trials of anticancer agents. The RECIST criteria are specified e.g. in Eisenhauer et al., New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1), European Journal Of Cancer 45 (2009) 228 – 247. RECIST defines Progressive Disease (PD) as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. Stable disease is defined as neither sufficient shrinkage to qualify for Partial Response (at least a 30% decrease in the sum of diameters of target lesions), nor sufficient increase to qualify for PD, i.e. an increase of <20% is defined as stable disease. It will be appreciated that in this context “at least stable” includes an increase or decrease in the RECIST score of less than 20%. Thus the antibody may delay or prevent progression of the disease (e.g. delay or prevent appearance of one or more signs or symptoms or cancer, and / or inhibit the growth of cancer cells and / or prevent or reduce metastases), or ameliorate or promote remission of the disease (e.g. reduce or inhibit one or more sign or symptom of cancer, and / or kill cancer cells). Subjects Suitable subjects may include those diagnosed with cancer, e.g. a cancer that expresses HER2, such as, but not limited to, skin cancer (e.g. melanoma), lung cancer, prostate cancer, squamous cell carcinoma (such as head and neck squamous cell carcinoma), breast cancer (including, but not limited to basal breast carcinoma, ductal carcinoma and lobular breast carcinoma), leukemia (such as acute myelogenous leukemia and 11g23-positive acute leukemia), lymphoma, a neural crest tumour (such as an astrocytoma, glioma or neuroblastoma), ovarian cancer, colon cancer, stomach cancer (e.g. gastric or gastroesophageal junction (GEJ) adenocarcinoma), pancreatic cancer, bone cancer (such as a chordoma), glioma or a sarcoma (such as chondrosarcoma). Preferably the antibody is administered to treat a solid tumour. In some embodiments the cancer is breast cancer or gastric cancer, preferably breast cancer. Preferably the subject is human. In some embodiments, the subject is suffering from a metastatic cancer. For instance, in some embodiments the cancer is metastatic breast cancer or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Most preferably the cancer is metastatic breast cancer. A therapeutically effective amount of antibody will depend upon the severity of the disease and the general state of the patient’s health. A therapeutically effective amount of the antibody is that which provides either subjective relief of a symptom(s) or an objectively identifiable improvement as noted by the clinician or other qualified observer. These compositions can be administered in conjunction with another chemotherapeutic agent, either simultaneously or sequentially. Low HER2 expression The anti-HER2 antibody is used to treat a subject suffering from a low HER2-expressing tumor. Such subjects may be referred to as “low HER2 expressors”, in contrast to high HER2 expressors. The terms “low HER2-expressing tumor” and “low HER2 expressor” are well understood in the field of cancer therapy and are frequently used to describe specific patient groups (see e.g. Nicolo et al. Ther Adv Med Oncol 2023, Vol. 15: 1 –16; Tarantino et al., J Clin Oncol 2020; 38: 1951–1962). Thus the subgroup of patients having low tumor HER2 expression is clearly distinguished from high HER2 expressors. Low tumor HER2 expression may be determined using well known and standard techniques. Typically HER2 expression is determined in a biopsy or surgical specimen from the tumor. Techniques for obtaining surgical biopsy samples from tumor tissue are known in the art, as are histopathological techniques for processing such samples. For instance, biopsy tissue samples may be fixed with formalin and embedded in paraffin or processed fresh before sectioning and placement on microscope slides for light microscopy analysis and imaging. HER2 expression levels may be detected using immunohistochemical techniques. Haemotoxylin and eosin (H&E) staining of paraffin-embedded sections is the default technology to visualize tissue on a glass slide for pathology analysis. Immunohistochemistry (IHC) staining is a well-known approach to identify expression of proteins on cells in pathology tissue slides. The staining results in a typical brown appearance of tissue where the targeted protein is overexpressed as compared to normal. For example, by using an antibody against HER2, its expression levels can be detected. Low HER2 expression may be defined as e.g. a HER2 IHC score of less than 3+, e.g.0, 1+ or 2+. Preferably the tumor has a HER2 IHC score of 1+ or 2+, more preferably 1+. In an alternative embodiment, the tumor has a HER2 IHC score of 0. Immunohistochemical detection of HER2 in a sample from the subject may be performed using a Dako anti-HER2 immunohistochemistry system (i.e. HercepTest™). The HercepTest™ method is described e.g. in FDA Premarket approval applications P980018, approved 25 September 1998 and P980018 / S010, approved 20 October 2010, and in Dako HercepTest™, Code K5204. Instruction for Use, (PD04086US_02 / K520421-5). The HercepTest™ method and alternative methods for detecting HER2 expression in tumors are also described in e.g. Jørgensen et al., (2021) Front. Oncol.11:676939. Various studies describe methods for detecting HER2 in tumor samples and the standardization of the results thereof. See in particular the American Society of Clinical Oncology–College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer (2018 version and 2023 update, see Wolff et al. Arch Pathol Lab Med (2023), Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer, available at https: / / doi.org / 10.5858 / arpa.2023-0950-SA and www.asco.org / breast-cancer- guidelines). See also e.g. Fitzgibbons et al., Arch Pathol Lab Med.2014;138:595–601; Canda et al., Eur J Breast Health. 2018 Jul; 14(3): 160–165; Dowsett et al., Modern Pathology. 2007;20:584–591; Zhang et al. Curr Oncol Rep 2020 Apr 29;22(5):51. The FDA-approved classification of HER2 IHC staining scores is described below: Score Surgical Specimen - Biopsy Specimen -Staining HER2 Staining Pattern Pattern Overexpression Assessment 0 No reactivity observed or No reactivity or no Negative weak membranous membranous reactivity in any reactivity observed in < (or < 5 clustered) tumor cell 10% of tumor cells 1+ Faint / barely perceptible membranous Tumor cell Negative membranous reactivity in ≥ cluster (≥ 5 cells) with a 10% of tumor cells; cells are faint / barely perceptible reactive only in part of their reactivity irrespective of membrane percentage of tumor cells stained 2+ Weak to moderate complete, Tumor cell cluster (≥ 5 cells) Equivocal basolateral or lateral with a weak to moderate membranous reactivity in complete, basolateral or lateral ≥10% of tumor cells membranous reactivity irrespective of percentage of tumor cells stained 3+ Strong complete, basolateral Tumor cell cluster (≥ 5 cells) Positive or lateral membranous with a strong complete, reactivity in ≥ 10% of tumor basolateral or lateral cells membranous reactivity irrespective of percentage of tumor cells stained Any suitable anti-HER2 antibody may be used in such methods, e.g. an anti-HER2 IgG antibody (polyclonal or monoclonal). Various anti-HER2 antibodies suitable for use in immunohistochemistry are available from commercial sources. Thus by “low HER2-expressing tumor” it is typically meant that less than 10% of tumor cells in a sample from the subject show strong complete membrane staining for HER2 (i.e. corresponding to a HER2 IHC score of less than 3+. Preferably the tumor sample lacks a tumor cell cluster (≥ 5 cells) with strong complete membrane staining for HER2. These levels of expression typically refer to membrane HER2 expression that is detectable by immunohistochemistry, e.g. using the methods described above. For instance in some embodiments, at least 10% of tumor cells or a tumor cell cluster (5 or more cells) in a sample from the subject show weak to moderate complete membrane staining for HER2, i.e. corresponding to a HER2 IHC score of 2+ using immunohistochemical detection of HER2. In some embodiments, a tumor cell cluster (5 or more cells) in a sample from the subject may show weak to moderate complete membrane staining for HER2. In other embodiments, at least 10% of tumor cells in a sample from the subject show faint or barely perceptible partial (incomplete) membrane staining for HER2, i.e. corresponding to a HER2 IHC score of 1+ using immunohistochemical detection of HER2. In some embodiments, a tumor cell cluster (5 or more cells) from the subject may show faint or barely perceptible partial (incomplete) membrane staining for HER2. In these embodiments, the tumor does not meet the criteria for a HER2 IHC score of 2+ or above, i.e. less than 10% of tumor cells in a sample from the subject show weak to moderate complete membrane staining for HER2 (and no tumor cell cluster (5 or more cells) showing weak to moderate complete membrane staining for HER2 is present). In alternative embodiments, tumor HER2 expression in the subject may be compared to that in a population of cancer subjects. Typically the population of cancer subjects refers to other subjects suffering from the same type of cancer. Thus the relative level of tumor HER2 expression in the subject, compared to other subjects with the same type of cancer, may be ascertained. Since this method does not require an absolute quantitation of HER2 expression levels, but only a relative determination compared to other cancer subjects, any systematic bias due to lack of standardization of expression detection is avoided. In preferred embodiments, tumor (e.g. membrane) HER2 expression in the subject is lower than in at least 50% of cancer subjects. Preferably membrane HER2 expression in tumor cells of the subject is lower than in at least 60%, at least 70% or at least 80% of cancer subjects, e.g. in subjects suffering from the same form of cancer (e.g. ovarian cancer). More preferably tumor membrane HER2 expression in the subject is lower than in at least 50%, 60%, 70%, 80% or at least 90% of HER2-expressing tumors (e.g. in HER2-expressing breast tumors). In some embodiments the tumor expresses HER2, i.e. the tumor shows at least some HER2 expression. Typically this means that tumor cells in the subject show detectable membrane HER2 expression, e.g. by immunohistochemistry. More preferably at least 1% or at least 5% of tumor cells in the subject show detectable (e.g. membrane) HER2 expression, e.g. using immunohistochemical detection of HER2. In other embodiments at least 10%, 15% or 20% of tumor cells in the subject show detectable membrane HER2 expression. Thus the tumor may have a HER 2 IHC score of 1+ or 2+ (in preference to 0). Preferably the determination of HER2 expression is made on a recent tumor biopsy sample, i.e. a biopsy sample obtained from the subject shortly before the start of anti-HER2 IgE treatment (rather than an old or archived sample). For instance, the biopsy sample may be obtained and / or HER2 expression determined less than 6 months, 3 months, 1 month, 2 weeks, 1 week, 3 days, 48 hours or 24 hours before the start of anti- HER2 IgE treatment. In some embodiments, amplification of the erbB2 (neu) gene may also be monitored. For instance, in situ hybridization (ISH, including e.g. fluorescence ISH or FISH) can be performed on a tumor sample from the subject to detect HER2-encoding gene amplification. In FISH, the HER2 gene copy number in relevant tumor cells may be determined and reported relative to the copy number of a centromere 17 (CEN17) reference probe determined in the same cells (e.g. using the PathVysion® HER2 DNA Probe Kit (Abbott Diagnostics) or HER2 FISH pharmDx (Dako)). A HER2 / CEN17 ratio ≥ 2.0 may be used as cut-off value indicative of HER2 amplification by FISH (see e.g. D’Alfonso et al., J Clin Pathol (2013) 66:409–14; and Jørgensen and Winther, The Development of the HercepTest - From Bench to Bedside. In: Jørgensen JT, Winther H, editors. Molecular Diagnostics – The Key Driver of Personalized Cancer Medicine. Singapore: Pan Stanford Publishing (2010). Thus in some embodiments, the tumor lacks erbB2 gene amplification. For example, a tumor sample from the subject may show no detectable amplification of a HER2-encoding gene (erbB2), e.g. as determined by FISH, or may show a HER2 / CEN17 ratio < 2.0. Additional diagnostic methods for analysing HER2 expression in combination with anti-HER2 treatment have been described. The table below shows FDA approved companion diagnostics assays for HER2 targeted drugs. This includes IHC and (fluorescent) in situ hybridization assays, as well as newer next generation sequencing (NGS) assays. Assay Manufacturer Breast cancerGastriccancer IHC Assays Bond Oracle HER2 IHC System Leica Biosystems Trastuzumab HercepTest™Agilent Technologies / Dako Trastuzumab Trastuzumab Denmark Pertuzumab Ado-trastuzumab emtansine InSite™ Her-2 / neu KITBiogenex LaboratoriesTrastuzumabPATHWAY anti-Her2 / neu Ventana Medical Systems Trastuzumab Ado-trastuzumab emtansine ISH Assays HER2 FISH pharmDx Kit Agilent Technologies / Dako Trastuzumab Trastuzumab Denmark Pertuzumab Ado-trastuzumab emtansine HER2 CISH Agilent Technologies / Dako Trastuzumab pharmDx Kit Denmark Ventana Medical Trastuzumab INFORM™HER- Systems Trastuzumab 2 / neu INFORM™HER2 Dual ISH DNA Ventana Medical Systems Ado-trastuzumab emtansine Probe Cocktail PathVysion®HER-2 DNA ProbeAbbott MolecularTrastuzumabKit SPOT-LIGHT® HER2 CISH KitLife Technologies Corporation TrastuzumabVENTANA HER2 Dual ISH DNA Ventana Medical Systems Trastuzumab Probe Cocktail NGS Assays FoundationOne®CDxFoundation MedicineTrastuzumab Pertuzumab Ado-trastuzumab emtansine The invention will now be further described by way of example only, with reference to the following non-limiting embodiments. EXAMPLES Anti-HER2 IgE antibodies The following anti-HER2 IgE antibodies were used in the examples. Table 1 Heavy chain (HC) CDR loops HC Light chains (LC) CDR loops LC - variable domain (VH) is (Chothia) – variable domain (Chothia) bold and underlined (VL) is bold and - constant (CH) domain is underlined standard text - constant (CL) domain is standard text Human EVQLVESGGGLVQPGG CDRH1 GFNIKDT DIQMTQSPSSLS CDRL1 Trastuz SLRLSCAASGFNIKDTYI (SEQ ID NO:3) ASVGDRVTITCR RASQDVNTAVA umab- HWVRQAPGKGLEWVA ASQDVNTAVAW (SEQ ID NO:8) IgE RIYPTNGYTRYADSVK CDRH2 YPTNGY YQQKPGKAPKL GRFTISADTSKNTAYLQ (SEQ ID NO:4) LIYSASFLYSGV CDRL2 SASFLYS MNSLRAEDTAVYYCSR PSRFSGSRSGTD (SEQ ID NO:9) WGGDGFYAMDYWGQ CDRH3 FTLTISSLQPED GTLVTVSSASTQSPSVFP WGGDGFYAMDY FATYYCQQHYT CDRL3 LTRCCKNIPSNATSVTLG (SEQ ID NO:5) TPPTFGQGTKV QQHYTTPPT CLATGYFPEPVMVTWDT EIKRTVAAPSVFI (SEQ ID NO:10) GSLNGTTMTLPATTLTLS FPPSDEQLKSGT GHYATISLLTVSGAWAK ASVVCLLNNFYP QMFTCRVAHTPSSTDWV REAKVQWKVDN DNKTFSVCSRDFTPPTVK ALQSGNSQESVT ILQSSCDGGGHFPPTIQLL EQDSKDSTYSLS CLVSGYTPGTINITWLED STLTLSKADYEK GQVMDVDLSTASTTQEG HKVYACEVTHQ ELASTQSELTLSQKHWLS GLSSPVTKSFNR DRTYTCQVTYQGHTFED GEC STKKCADSNPRGVSAYL SRPSPFDLFIRKSPTITCL LC - SEQ ID NO:6 VVDLAPSKGTVNLTWSR VL - SEQ ID NO:7 ASGKPVNHSTRKEEKQR CL–SEQ ID NO:42 NGTLTVTSTLPVGTRDWI EGETYQCRVTHPHLPRA LMRSTTKTSGPRAAPEV YAFATPEWPGSRDKRTL ACLIQNFMPEDISVQWL HNEVQLPDARHSTTQPR KTKGSGFFVFSRLEVTRA EWEQKDEFICRAVHEAA SPSQTVQRAVSVNPGK HC – SEQ ID NO:1 VH - SEQ ID NO:2 CH – SEQ ID NO:41 Rat EVQLVESGGGVVQPGR CDRH1 GFTFSSY DIVMTQSPLSLP CDRL1 V20 SLRLSCAASGFTFSSYG (SEQ ID NO:13) VTPGQPASMSC NSSQSLIYSDGN IgE MHWVRQAPGKGLEWV NSSQSLIYSDGN TYLN ANIKPDGGAEYYGDAV CDRH2 KPDGGA TYLNWFQQRPG (SEQ ID NO:18) RGRFTISRDNARNSLYL (SEQ ID NO:14) QSPRRLIYKVSN QMNSLRAGDTAVYYCA RDSGVPDRFSGS CDRL2 RDRGYYGMDVWGQGT CDRH3 GSGTDFTLKISR KVSNRDS TVTVSSVSVKAPSLYPLK DRGYYGMDV VEAEDVGIYYC (SEQ ID NO:19) PCSSENTASVTLGCLVKD (SEQ ID NO:15) MQGAHWPPTF YFPDPVTVTWYSDSLNT GQGTKVEIKRA CDRL3 STMNFPSVGSDLKTTTSQ DAAPTVSIFPPSM MQGAHWPPT MTSWGKSAKNFTCHVT EQLTSGGATVVC (SEQ ID NO:20) HAPSTFVSDLTIRARPVNI FVNNFYPRDISV TKPTVDLLHSSCDPNAFH KWKIDGSEQRD STIQLYCFVYGHIQNDVS GVLDSVTDQDSK IHWLMDDRKIYETHAQN DSTYSMSSTLSL VLIKEEGKLASTYSRLNI TKVEYERHNLYT TQQQWMSESTFTCKVTS CEVVHKTSSSPV QGENYWAHTRRCSDDEP VKSFNRNEC RGVITYLIPPSPLDLYENG TPKLTCLVLDLESEENIT LC -SEQ ID NO:16 VTWVRERKKSIGSASQR VL -SEQ ID NO:17 STKHHNATTSITSILPVD AKDWIEGEGYQCRVDHP HFPKPIVRSITKAPGKRS APEVYVFLPPEEEEKDKR TLTCLIQNFFPEDISVQW LQDSKLIPKSQHSTTTPL KYNGSNQRFFIFSRLEVT KALWTQTKQFTCRVIHE ALREPRKLERTISKSLGN TSLRPSQASM HC – SEQ ID NO:11 VH - SEQ ID NO:12 Rat EVQLVQSGAEVKKPGA CDRH1 GYTFTSY DIVMTQTPLSLP CDRL1 V23 SVKVSCKASGYTFTSYG (SEQ ID NO:23) VTPGQPASISCR RSSQSLVYSDG IgE ISWVRQAPGQGLEWM SSQSLVYSDGNT NTYLN GWISAYNGNTNYAQKL CDRH2 SAYNGN YLNWFQQRPG (SEQ ID NO:28) QGRVTMTTDTSTSTAY (SEQ ID NO:24) QSPRRLIYKVSN MELRSLRSDDTAVYYC RDSGVPDRFSGS CDRL2 ARHRGYYGMDVWGRG CDRH3 GSGTDFTLKISR KVSNRDS TLVTVSSVSVKAPSLYPL HRGYYGMDV VEAEDVGLYYC (SEQ ID NO:29) KPCSSENTASVTLGCLVK (SEQ ID NO:25) MQATHWPPAF DYFPDPVTVTWYSDSLN GQGTKLEIKRA CDRL3 TSTMNFPSVGSDLKTTTS DAAPTVSIFPPSM MQATHWPPA QMTSWGKSAKNFTCHV EQLTSGGATVVC (SEQ ID NO:30) THAPSTFVSDLTIRARPV FVNNFYPRDISV NITKPTVDLLHSSCDPNA KWKIDGSEQRD FHSTIQLYCFVYGHIQND GVLDSVTDQDSK VSIHWLMDDRKIYETHA DSTYSMSSTLSL QNVLIKEEGKLASTYSRL TKVEYERHNLYT NITQQQWMSESTFTCKV CEVVHKTSSSPV TSQGENYWAHTRRCSDD VKSFNRNEC EPRGVITYLIPPSPLDLYE NGTPKLTCLVLDLESEEN LC -SEQ ID NO:26 ITVTWVRERKKSIGSASQ VL -SEQ ID NO:27 RSTKHHNATTSITSILPVD AKDWIEGEGYQCRVDHP HFPKPIVRSITKAPGKRS APEVYVFLPPEEEEKDKR TLTCLIQNFFPEDISVQW LQDSKLIPKSQHSTTTPL KYNGSNQRFFIFSRLEVT KALWTQTKQFTCRVIHE ALREPRKLERTISKSLGN TSLRPSQASM HC – SEQ ID NO:21 VH - SEQ ID NO:22 Rat QVQLVQSGAEVKKPGA CDRH1 GYTFTSY QSVLTQPASVSG CDRL1 V26 SVKVSCKASGYTFTSYA (SEQ ID NO:33) SPGQSITISCTGT TGTSSDVGSYN IgE MHWVRQAPGQRLEWI SSDVGSYNLVS LVS GWINAGNGNTKYSQKF CDRH2 NAGNGN WYQQHPGKAP (SEQ ID NO:38) QGRVTITRDTSASTAY (SEQ ID NO:34) KLMIYEVSNRPS MELSSLRSEDTAVYYC GVSNRFSGSKSG CDRL2 ARDFSSQVATAAVDYW CDRH3 NTASLTISGLQA EVSNRPS GQGTLVTVSSVSVKAPS DFSSQVATAAVDY EDEADYYCSSY (SEQ ID NO:39) LYPLKPCSSENTASVTLG (SEQ ID NO:35) TSSSTLVFGGGT CLVKDYFPDPVTVTWYS KLTVLGQPKSTP CDRL3 DSLNTSTMNFPSVGSDL TLTVFPPSTEELQ SSYTSSSTLV KTTTSQMTSWGKSAKNF GNKATLVCLISD (SEQ ID NO:40) TCHVTHAPSTFVSDLTIR FYPSDVEVAWK ARPVNITKPTVDLLHSSC ANGAPISQGVDT DPNAFHSTIQLYCFVYGH ANPTKQGNKYIA IQNDVSIHWLMDDRKIY SSFLRLTAEQWR ETHAQNVLIKEEGKLAST SRNSFTCQVTHE YSRLNITQQQWMSESTF GNTVEKSLSPAE TCKVTSQGENYWAHTR CV RCSDDEPRGVITYLIPPSP LDLYENGTPKLTCLVLD LC -SEQ ID NO:36 LESEENITVTWVRERKKS VL -SEQ ID NO:37 IGSASQRSTKHHNATTSI TSILPVDAKDWIEGEGYQ CRVDHPHFPKPIVRSITK APGKRSAPEVYVFLPPEE EEKDKRTLTCLIQNFFPE DISVQWLQDSKLIPKSQH STTTPLKYNGSNQRFFIFS RLEVTKALWTQTKQFTC RVIHEALREPRKLERTIS KSLGNTSLRPSQASM HC – SEQ ID NO:31 VH - SEQ ID NO:32 Trastuzumab IgE is described in Karagiannis et al.2009, Cancer Immunol Immunother.2009 58(6): 915–930. V20, V23 and V26 IgE were generated using phage display methods. A panel of 100 antibodies from phage display was triaged on the basis of binding affinity to recombinant HER2 and HER2 on cell surfaces, retained binding to FcεR1, epitope specificity, rat / human HER2 cross-reactivity, ability to degranulate human FcεR1 expressing basophils, ability to kill tumour cells by ADCC and ADCP and assessments of biophysical properties (solubility and thermal stability). V23 competes with trastuzamab for binding to HER2, and thus binds to subdomain IV (the juxtamembrane region) of the extracellular domain of the HER2. V26 IgE competes with pertuzumab for binding to HER2, and thus binds to subdomain II (the dimerisation region) of the extracellular domain of the HER2. V20 does not compete with either trastuzamab or pertuzamab for binding to HER2. In the following studies, the above IgE antibodies targeting HER2 were profiled in vivo in humanised mouse and rat tumour models with low HER2 expression. Anti-HER2 IgE treatment of HER2 IHC 2+ tumors in humanised NXG mice A tumour model used in NXG mice humanised with peripheral blood mononuclear cells (PBMC) was established using JIMT1 cells. PrkdcscidIl2rgTm1 / Rj (NXG) mice carry loss-of- function mutations of the Prkdc and Il2rg genes on a NOD (nonobese diabetic) background and are severely immunodeficient (see e.g. Gillgrass et al., Front Immunol. 2020;11:617516; Radaelli et al., PLoS ONE. 2015;10(5):e0124974). Immunodeficient mice engrafted with human PBMC can be used to analyse human immune responses (see e.g. Yaguchi et al., Cell Mol Immunol.2018 Nov; 15(11): 953–962). JIMT1 cells are an established a carcinoma cell line derived from a pleural metastasis of a 62- year old patient with breast cancer who was clinically resistant to trastuzumab. JIMT1 cells are reported to have moderate to weak HER2 expression levels (HercepTest IHC 2+ by the clinically relevant quantification method) and were found to be resistant to both trastuzumab and pertuzumab in vitro and in xenograft tumors (Tanner et al., Mol Cancer Ther. 2004 Dec;3(12):1585-92). Analysis of HER2 expression on the cell surface using flow cytometry demonstrated that HER2 levels were lower in the JIMT1 cell line compared to the Herceptest IHC 3+ cell line SKBR3 (see Figure 1). Female NXG mice were implanted subcutaneously with JIMT1 cells (1x107 cells per mouse; 1:1 matrigel). Tumour volume was monitored via calliper three times weekly throughout the study. Once tumours reached a volume of 30-50mm3 mice were randomised into treatment groups of 12 mice. At this point peripheral blood mononuclear cells (PBMC; 5x106 cells per mouse; 3 donors per group) and Flt3L (10mg) were administered intravenously. Mice were dosed intravenously with 20mg / kg trastuzumab-IgE (for sequence see Table 1) or vehicle control (PBS) at the same time as PBMCs and twice weekly thereafter for a duration of 31 days. In these studies, trastuzumab-IgE (20mg / kg) resulted in a statistically significant tumour growth inhibition (60%) compared to PBS vehicle control (Figure 2). Anti-HER2 IgE treatment of HER2 IHC 1+ tumors in rats Three anti-HER2 IgE antibodies (V20, V23 and V26) were tested in the syngeneic Fischer rat / MTLn3 model (see e.g. Neri et al., J Natl Cancer Inst 68:507–517). MTLn3 is a very aggressive tumour cell line, quickly generating large tumours in the rat. In this syngeneic model, the MTLn3 cancer cell line (derived from a rat mammary carcinoma) is of the same genetic background as the host rat, in contrast to the humanized NXG mouse study described above (where a human cell line is transplanted into immunodeficient mice humanized with PBMC). Thus the host rat has a fully functioning, authentic immune system. The levels of HER2 on MTLn3 were assessed by flow cytometry and were shown to be lower than in either the JIMT1 or the SKBR3 cell lines (see Figure 3). MTLn3 cells are thus considered to have very low HER2 expression levels (equivalent to HercepTest IHC 1+ by the clinically relevant quantification method). Female Fisher 344 rats (4-5 weeks old) were implanted subcutaneously in proximity to the mammary fat pad with MTLn3 cells (0.7 x 106 cells per rat in PBS). Tumour volume was monitored via calliper three times weekly throughout the study. Once tumours reached a volume of 50-100mm3 rats were randomised into treatment groups of 12-13. Rats were dosed intravenously with 20mg / kg of HER2 targeting IgE antibodies V20, V23 or V26 (for sequences see Table 1) or vehicle control (PBS) twice weekly for 2.5 weeks. In these studies there was a varying degree of tumour growth inhibition across the HER2 targeting variants (ranging from 25.7 to 52.0%), with V26>V23>V20 (see Figure 4 and Table 2 below). Table 2 V20 V23 V26 Tumour Growth 25.7% 33.0% 52.0% Inhibition p value 0.0703 0.0109 <0.0001 V26 caused increased immune cell infiltration into the tumours, including neutrophils and monocytes (see Figures 5 and 6). V26 also caused increased tumour cell death, as evidenced by increased numbers of apoptotic cells (see Figures 6 and 7). Anti-HER2 IgE treatment of HER2 IHC 0 tumors in mice The triple negative breast cancer cell line MDA-MB-231 has ultra-low levels of HER2 expression (defined as Herceptest 0). MDA-MB-231 cells (1x107 cells 1:1 with Matrigel) were implanted subcutaneously into NXG mice. Once the tumours reached approximately 35- 50mm3 the mice were engrafted intravenously with human PBMC (5 x106 cells) with a FLT3L boost (10µg on 3 consecutive days) to enhance the myeloid component. Mice were dosed with with the PBMCs and then twice weekly thereafter. Tumour volume was assessed by caliper. Mice were dosed with 10mg / kg of the HER2 targeting IgE antibody V26 (for sequence see Table 1), an isotype control antibody (NIP IgE) or vehicle control (PBS) with the PBMCs and then twice weekly thereafter. Tumour volume was assessed by caliper. As shown in Figure 8 (in which “EPS 226” refers to the V26 IgE antibody), V26 statistically significantly reduces tumour growth compared to PBS and isotype controls in this model. This demonstrates the ability of a HER2 targeting IgE to be used to treat triple negative breast cancer. These data demonstrate the ability of a HER2 targeting IgE to significantly impact on tumour growth in the context of low HER2 expression. All publications mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described methods and system of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the present invention. Although the present invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in the art are intended to be within the scope of the following claims.

Claims

CLAIMS 1. An anti-HER2 immunoglobulin E (IgE) antibody for use in treating a low HER2- expressing tumor in a subject.

2. An IgE antibody for use according to claim 1, wherein less than 10% of tumor cells in a sample from the subject show strong complete membrane staining for HER2 using immunohistochemical detection of HER2.

3. An IgE antibody for use according to claim 1 or claim 2, wherein using immunohistochemical detection of HER2, at least 10% of tumor cells or a tumor cell cluster (5 or more cells) in a sample from the subject show weak to moderate complete membrane staining for HER2.

4. An IgE antibody for use according to claim 1 or claim 2, wherein using immunohistochemical detection of HER2, at least 10% of tumor cells or a tumor cell cluster (5 or more cells) in a sample from the subject show faint or barely perceptible partial membrane staining for HER2.

5. An IgE antibody for use according to any preceding claim, wherein immunohistochemical detection of HER2 in a sample from the subject is performed using a Dako anti-HER2 immunohistochemistry system (HercepTest™); preferably wherein a tumor sample from the subject has a HER2 immunohistochemical staining (HER2 IHC) score of 2+ or lower, more preferably 2+ or 1+.

6. An IgE antibody for use according to any preceding claim, wherein the tumor has a HER2 / CEN17 ratio < 2.0 or shows no detectable erbB2 gene amplification as determined by fluorescence in situ hybridization.

7. An IgE antibody for use according to any preceding claim, wherein tumor HER2 expression in the subject is lower than in at least 50% of cancer subjects; preferably wherein membrane HER2 expression in tumor cells of the subject is lower than in at least 60%, at least 70% or at least 80% of subjects suffering from the same form of cancer; more preferably wherein tumor HER2 expression in the subject is lower than in at least 50%, at least 70% or at least 90% of HER2-expressing tumors (preferably HER2-expressing breast tumors).

8. An IgE antibody for use according to any preceding claim, wherein the tumor expresses HER2; preferably wherein at least 1%, 5%, 10%, 15% or 20% of tumor cells in the subject show detectable membrane HER2 expression using immunohistochemical detection of HER2.

9. An IgE antibody for use according to any preceding claim, wherein the antibody binds to subdomain II of the extracellular domain of the HER2, preferably wherein the antibody at least partially competes with pertuzumab IgG for binding to HER2.

10. An IgE antibody for use according to any preceding claim, wherein the antibody binds to subdomain IV of the extracellular domain of the HER2, preferably wherein the antibody at least partially competes with trastuzumab IgG for binding to HER2.

11. An IgE antibody for use according to any preceding claim, wherein the antibody is trastuzumab IgE.

12. An IgE antibody for use according to any preceding claim, wherein the antibody comprises an amino acid sequence as defined in any one of SEQ ID NO:s 1 to 40.

13. An IgE antibody for use according to claim 12, wherein the antibody comprises one to six CDR sequences selected from: (i) SEQ ID NOs: 3, 4, 5, 8, 9 and 10; (ii) SEQ ID NOs: 13, 14, 15, 18, 19 and 20; (iii) SEQ ID NOs: 23, 24, 25, 28, 29 and 30; or (iv) SEQ ID NOs: 33, 34, 35, 38, 39 and 40.

14. An IgE antibody for use according to claim 12 or claim 13, wherein the antibody comprises: (i) a heavy chain variable domain sequence as defined in any one of SEQ ID NOs: 2, 12, 22 or 32; (ii) a light chain variable domain sequence as defined in any one of SEQ ID NOs: 7, 17, 27 or 37; (iii) a heavy chain sequence as defined in any one of SEQ ID NOs: 1, 11, 21 or 31; and / or (iv) a light chain sequence as defined in any one of SEQ ID NOs: 6, 16, 26 or 36.

15. An IgE antibody for use according to any preceding claim, for use in treating and / or delaying progression of cancer in the subject.

16. An IgE antibody for use according to any preceding claim, wherein the tumor or cancer is a breast tumor or breast cancer.

17. An IgE antibody for use according to any preceding claim, wherein the antibody lacks a cytotoxic moiety, preferably wherein the antibody is not an antibody-drug conjugate (ADC).

18. A method for treating and / or delaying progression of cancer in a subject having a low HER2-expressing tumor, the method comprising a step of administering an anti-HER2 immunoglobulin E (IgE) antibody as defined in any preceding claim to the subject in a therapeutically-effective amount.

19. A pharmaceutical composition for use in treating a low HER2-expressing tumor in a subject, comprising an anti-HER2 immunoglobulin E (IgE) antibody as defined in any of claims 1 to 17 and one or more pharmaceutically acceptable excipients, carriers or diluents.

20. An immunoglobulin, or a functional fragment thereof, comprising one to six CDR sequences selected from: (i) SEQ ID NOs: 13, 14, 15, 18, 19 and 20; (ii) SEQ ID NOs: 23, 24, 25, 28, 29 and 30; or (iii) SEQ ID NOs: 33, 34, 35, 38, 39 and 40.

21. An immunoglobulin or functional fragment thereof according to claim 20, wherein the immunoglobulin comprises: (i) a heavy chain variable domain sequence as defined in any one of SEQ ID NOs: 12, 22 or 32; (ii) a light chain variable domain sequence as defined in any one of SEQ ID NOs: 17, 27 or 37; (iii) a heavy chain sequence as defined in any one of SEQ ID NOs: 11, 21 or 31; and / or (iv) a light chain sequence as defined in any one of SEQ ID NOs: 6, 16, 26 or 36.

22. An immunoglobulin or functional fragment thereof according to claim 20 or claim 21, wherein the immunoglobulin is of isotype IgE.

23. An immunoglobulin or functional fragment thereof according to any of claims 20 to 22, wherein the immunoglobulin is a chimaeric or humanized antibody, preferably comprising one or more human framework regions and / or one or more human IgE heavy and / or light chain constant domains.

Images