An antibody-based strategy targeting activated oncogenic ERG in prostate cancer

Abstract

The present invention relates to antibodies or antigen-binding portion thereof that are capable of specifically binding to a methylated ETS transcription factor ERG, for use in the prophylactic and / or therapeutic treatment of a prostate cancer in a subject in need thereof. The invention relates also to the use of such antibodies or an antigen-binding portion thereof in the diagnosis or prognosis of prostate cancer.

Description

An antibody -based strategy targeting activated oncogenic ERG in prostate cancerDESCRIPTIONTechnical field of the inventionThe present invention relates to antibodies or antigen-binding portion thereof that are capable of specifically binding to a methylated ETS transcription factor ERG, in particular for use in the prophylactic and / or therapeutic treatment of a prostate cancer in a subject in need thereof. The invention relates also to the use of such antibodies or an antigen-binding portion thereof in the diagnosis or prognosis of prostate cancer.State of the artProstate cancer is a leading cause of cancer death worldwide and the most common cancer in men. A recurrent gene fusion involving the ETS transcription factor ERG and the 5' region of the TMPRSS2 gene occurs in more than half of prostate cancers. This TMPRSS2:ERG gene fusion results in overexpression of the ERG protein driven by the androgen responsive TMPRSS2 promoter in prostate cancer cells. Interestingly, high ERG expression occurs exclusively in primary prostate tumors with the TMPRSS2:ERG gene fusion and is retained in treatment-resistant (hormone-refractory) prostate cancers, making ERG an actionable target for developing potentially broadly effective therapeutics at multiple stages of prostate cancer clinical evolution.Nevertheless, transcription factors are difficult or undruggable targets for conventional small-molecule drugs. Attempts have been made to block ERG with small-molecule compounds and short peptides. These approaches have been tested in preclinical models, but their clinical translation may be limited by poor potency and selectivity.Accordingly, there is still an urgent need in the field for the development of effective therapeutic agent for use in the prophylactic and / or therapeutic treatment of prostate cancer.Summary of the InventionAs will be further detailed in the experimental section of the present specification, the inventors have surprisingly found that interfering selectively with methylated ERG activity using an antibody or an antigen binding portion thereof represents a valid strategy to treatand prevent further progression of prostate cancer, in particular those positive for the TMPRSS2:ERG gene fusion (ERG-positive prostate cancers).To overcome the limitation of the state of the art, the present invention specifically provides an antibody or an antigen binding portion thereof that selectively recognizes the methylated form of ERG protein (herein abbreviated as mERG MoAb), which is the active oncogenic form of ERG uniquely present in ERG fusion -positive prostate tumors.The strategy proposed by the authors of the invention advantageously couples the high affinity of binding of the antibodies, in particular monoclonal antibody or an antigen binding portion thereof (i.e., many folds higher than any small molecule compound) to the ability to recognize the modified, oncogenic state of the target protein selectively. Furthermore, the target (i.e., ERG methylated specifically at the identified lysine residue) is present only in ERG fusion-positive tumoral cells, decreasing the risk of off-tumor on-target effects.According to the approach provided by the present invention, the efficacy and selectivity of the anti-mERG antibody are further increased by delivering the antibody intracellularly as DNA / mRNA expression construct that produces a single-chain and / or mini-antibody in the cells. The experimental data provided by the authors of the invention support the feasibility of this approach and efficient intracellular production of the anti-mERG antibody. Moreover, the results obtained by the inventors show the ability of the intracellular anti-mERG miniantibody to block ERG oncogenic activity and affect positively the cancer cell phenotype in relevant in vitro and in vivo preclinical models of prostate cancer.The anti-mERG MoAb provided by the invention represents an important tool to further understand the role of methylated ERG in cancer progression and provides highly selective anticancer therapies for ERG fusion-positive prostate tumors.Notably, there is no other mERG-specific monoclonal antibody available worldwide, and no attempt has been reported to generate an ERG-blocking antibody in general.In certain aspects, the invention thus provides an antibody or an antigen-binding portion thereof, preferably a human antibody or an antigen-binding portion thereof, capable of specifically binding to the methylated ERG protein (also abbreviated throughout the present specification as an anti-mERG antibody), in particular to an epitope of said methylated protein comprising a methylated lysine residue, as well as its use in a prophylactic and / or therapeutic treatment of a prostate cancer in a subject in need thereof. According to a preferred embodiment, said prostate cancer is an ERG-positive prostate cancer.In certain aspects, the invention provides an isolated nucleic acid molecule comprising a nucleotide sequence that encodes the antibody or an antigen-binding portion thereof according to any one of the embodiments herein disclosed, as well as its use in a prophylactic and / or therapeutic treatment of a prostate cancer in a subject in need thereof, in particular an ERG- positive prostate cancer.In certain aspects, the invention provides an isolated ribonucleic acid molecule comprising a nucleotide sequence that translates the antibody or an antigen-binding portion thereof according to any one of the embodiments herein disclosed, as well as its use in a prophylactic and / or therapeutic treatment of a prostate cancer in a subject in need thereof, in particular an ERG- positive prostate cancer.In certain aspects, the invention provides a vector comprising a nucleic acid molecule encoding the antibody or an antigen-binding portion thereof according to any one of the embodiments herein disclosed, wherein the vector optionally comprises an expression control sequence operably linked to the nucleic acid molecule.In certain aspects, the invention provides a nanoparticle, in particular a lipid nanoparticle, comprising a nucleic acid molecule or ribonucleic acid molecule, encoding or translating the antibody or an antigen-binding portion thereof according to any one of the embodiments herein disclosed, wherein the vector optionally comprises an expression control sequence operably linked to the nucleic acid molecule.In certain aspects, the invention provides a method of preventing or treating a prostate cancer or conditions or disorders resulting from such disease, comprising administering an antibody or an antigen-binding portion thereof, or else a nucleic acid, a ribonucleic acid, a nanoparticle, or a vector according to any embodiments herein disclosed, to a subject in need thereof.The invention further provides an antibody or an antigen-binding portion thereof, or a nucleic acid molecule or a vector according or a ribonucleic acid or a nanoparticle or a vector according to any embodiments herein disclosed for use in the diagnosis, prophylaxis and / or treatment of a subject having, or at risk of developing, a prostate cancer, in particular an ERG-positive prostate cancer. Furthermore, the invention pertains to the use of the antibodies and / or the nucleic acid molecules of the invention in the diagnosis / detection of such prostate cancers.In certain aspects, the invention provides a pharmaceutical composition comprising at leastone or more antibodies or an antigen-binding portion thereof, or one or more nucleic acid molecules or a ribonucleic acid or a nanoparticle or a vector or vectors according to any one of the embodiments herein disclosed and a pharmaceutically acceptable carrier, as well as its use in the prevention and / or treatment of a prostate cancer in a subject in need thereof, in particular an ERG-positive prostate cancer.In certain aspects, the invention provides an isolated cell line that produces the antibody or an antigen-binding portion thereof according to any one of the embodiments herein disclosed, in particular a hybridoma cell line.The invention further provides the use of a vector according to any of the embodiments disclosed herein in a prophylactic and / or therapeutic treatment of a prostate cancer in a subject in need thereof.In certain aspects, the invention provides a non-human transgenic animal or transgenic plant comprising the nucleic acid molecule or vector comprising said nucleic acid molecule according to any one of the preceding embodiments, wherein the non-human transgenic animal or transgenic plant expresses said nucleic acid. In certain embodiments, said non-human transgenic animal is a mammal.In certain aspects, the invention provides the in vitro use of a methylated ERG protein, in particular an ERG protein comprising the methylated lysine residue in position K362, as a biomarker for the diagnosis and / or prognosis and / or to monitor the development of a prostate cancer in a subject, in particular wherein said cancer is an ERG-positive prostate cancer.In certain aspects, the invention provides an in vitro method for revealing the presence of a methylated ERG protein, preferably an ERG protein comprising the methylated lysine residue in position K362, in a sample comprising the following steps: i) Contacting an antibody or an antigen-binding portion thereof according to any one of the embodiments herein disclosed. ii) Detecting the binding of said antibody or antigen-binding portion thereof with the methylated ERG protein.In certain aspects, the invention provides an in vitro method for the diagnosis and / or prognosis and / or to monitor the development of a prostate cancer in a subj ect comprising the following steps: i) determining and / or quantifying the expression levels of a methylated ERG protein, preferably an ERG protein comprising the methylated lysine residue in position K362, in a sample isolated from said subject; preferably wherein said cancer is fusion positive prostate cancer.In certain aspects, the invention further provides a diagnostic or prognostic kit comprising as a specific reagent an antibody or an antigen-binding portion thereof according to any of the embodiments disclosed herein. Preferably, said kit is for use in a method for determining and / or quantifying, in a sample isolated from a subject, the expression levels of a methylated ERG protein according to any of the variants disclosed herein.The invention contemplates combinations of any of the foregoing aspects and embodiments of the invention.Brief description of the drawingsFig. 1 - A) ERG in complex with DNA (PDB 4IRI) The peptide used for immunization is shown in red. K362 is shown in dark blue B) Performance of the newly generated monoclonal antibody (13H2-1) Top ELISA of WT-P15 together with mono-, di- and trimethylated peptides. Bottom ELISA of METH-P15 together with two randomly scrambled peptides and a peptide from ROR alpha. C) Schematic representation of an IgG antibody and of a small-chain Fv. D) Schematic representation of the two scFv-13H2-l constructs.Fig. 2 - In vivo antitumor effect of the anti-mERG antibody. A) Scheme of the experiment B) Growth of the EPG2 tumor xenografts C) Ex-vivo tumor sphere formation from explanted EPG2 tumors D) Evaluation of mERG protein level In tumor xenografts by Immunohistochemistry. E-F) Evaluation of cleaved caspase 3 by immunohistochemistry (E) and western blotting (F).Detailed description of the inventionUnless otherwise defined herein, scientific, and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. Generally, nomenclature used in connection with, and techniques of, cell and tissue culture, molecular biology, immunology, microbiology, genetics and protein and nucleic acid chemistry and hybridization described herein are those well-known and commonly used in the art. The methods and techniques of the present invention are generally performed according to conventional methods well known in the art and as described in various general and morespecific references that are cited and discussed throughout the present specification unless otherwise indicated. See, e.g., Sambrook et al. Molecular Cloning: A Laboratory Manual, second ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989) and Ausubel et al, Current Protocols in Molecular Biology, Greene Publishing Associates (1992), and Harlow and Lane Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1990), incorporated herein by reference.The following terms, unless otherwise indicated, shall be understood to have the following meanings:The term "polypeptide" encompasses native or artificial proteins, protein fragments and polypeptide analogues of a protein sequence. A polypeptide may be monomeric or polymeric. The term "isolated protein", "isolated polypeptide" or "isolated antibody" is a protein, polypeptide or antibody that by virtue of its origin or source of derivation (1) is not associated with naturally associated components that accompany it in its native state, (2) is free of other proteins from the same species, (3) is expressed by a cell from a different species, or (4) does not occur in nature. Thus, a polypeptide that is chemically synthesized or synthesized in a cellular system different from the cell from which it naturally originates will be "isolated" from its naturally associated components. A protein may also be rendered substantially free of naturally-associated components by isolation, using protein purification techniques well known in the art. Examples of isolated antibodies include an anti-mERG antibody that has been affinity purified using methylated ERG proteins or a portion thereof such as any of the peptides exemplified in the present specification and in the claims, an anti-mERG antibody that has been synthesized by a hybridoma or other cell line in vitro, and a human monol onal antibody derived from a transgenic animal.A protein or polypeptide is "substantially pure", "substantially homogeneous", or "substantially purified" when at least about 60 to 75% of a sample exhibits a single polypeptide. The polypeptide or protein may be monomeric or multimeric. A substantially pure polypeptide or protein will typically comprise about 50%, 60%, 70%, 80% or 90% W / W of a protein sample, more usually about 95%, and preferably will be over 99% pure. Protein purity or homogeneity may be indicated by a number of means well known in the art, such as polyacrylamide gel electrophoresis of a protein sample, followed by visualizing a single polypeptide band upon staining the gel with a stain well known in the art. For certain purposes, higher resolution may be provided by using HPLC or other means well known inthe art for purification. The term "polypeptide fragment" as used herein refers to a polypeptide that has an amino-terminal and / or carboxy-terminal deletion, but where the remaining amino acid sequence is identical to the corresponding positions in the naturally occurring sequence. In some embodiments, fragments are at least 5, 6, 8 or 10 amino acids long. In other embodiments, the fragments are at least 14, at least 20, at least 50, or at least 70, 80, 90, 100, 150 or 200 amino acids long. The term "polypeptide analogue" as used herein refers to a polypeptide that comprises a segment that has substantial identity to a portion of an amino acid sequence and that has at least one of the following properties: (1) specific binding to a methylated ERG protein or epitopes thereof according to any of variants disclosed herein under suitable binding conditions, (2) ability to inhibit prostate tumor growth.Typically, polypeptide analogues comprise a conservative amino acid substitution (or insertion or deletion) with respect to the native sequence. Analogues typically are at least 20 or 25 amino acids long, preferably at least 50, 60, 70, 80, 90, 100, 150 or 200 amino acids long or longer, and can often be as long as a full-length polypeptide. Some embodiments of the invention include polypeptide fragments or polypeptide analogue antibodies with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 substitutions from the germline amino acid sequence. In certain embodiments, amino acid substitutions to an anti-mERG antibody or antigen-binding portion thereof are those which: (1) reduce susceptibility to proteolysis, (2) reduce susceptibility to oxidation, (3) alter binding affinity to form protein complexes, and (4) confer or modify other physicochemical or functional properties of such analogues, but still retain specific binding to a methylated ERG protein or epitopes thereof according to any of the variants disclosed in the present specification. Analogues can include various muteins of a sequence other than the normally occurring peptide sequence. For example, single or multiple amino acid substitutions, preferably conservative amino acid substitutions, may be made in the normally occurring sequence, preferably in the portion of the polypeptide outside the domain(s) forming intermolecular contacts. A conservative amino acid substitution should not substantially change the structural characteristics of the parent sequence; e.g., a replacement amino acid should not alter the anti-parallel [beta]-sheet that makes up the immunoglobulin binding domain that occurs in the parent sequence, or disrupt other types of secondary structure that characterizes the parent sequence. In general, glycine and proline would not be used in an anti-parallel [beta]-sheet. Examples of art-recognizedpolypeptide secondary and tertiary structures are described in Proteins, Structures and Molecular Principles (Creighton, Ed., W. H. Freeman and Company, New York (1984)); Introduction to Protein Structure (C. Branden and J. Tooze, eds., Garland Publishing, New York, N.Y. (1991)); and Thornton et ai, Nature 354: 105 (1991), incorporated herein by reference.The term “ERG protein” as used herein refers to the transcriptional regulator ERG encoded by the ERG gene, which is a nuclear protein that binds purine-rich sequences of DNA, and is intended to encompass any isoform, variant, ortholog or homolog of said ERG protein. Transcriptional regulator ERG is required for platelet adhesion to the subendothelium and regulates hematopoiesis. It has a DNA binding domain and a PNT (pointed) domain. ERG is expressed at higher levels in early myelocytes than in mature lymphocytes (types of white blood cells). Therefore, ERG may act as a regulator of differentiation of early hematopoietic cells.In one preferred embodiment, the term “ERG protein” as used herein refers to the human ERG protein and is intended to encompass any isoform of the human ERG protein, such as for example ERG -1, ERG -2, ERG -3 / p55(Erg), p49(ERG) and p38(ERG). Most preferably, the term “ERG protein” refers to the human protein having the amino acid sequence set forth in SEQ ID No. 1.In the context of the present specification, the expression “wild type” when used with reference to an ERG protein indicates a native, non-methylated ERG protein, i.e. a native ERG protein that does not comprise a methylated amino acid residue as a post-translational modification.The term “ERG fusion-positive prostate cancer” as used herein means a prostate cancer that harbors a genomic translocation that leads to the fusion of the gene encoding ERG with the regulatory region (promoter) of the gene encoding TMPRSS2, a protease highly expressed in prostatic cells. The TMPRSS2:ERG gene fusion is the most frequent genetic rearrangement in prostate tumors and results in the ERG protein overexpression.Where an "antibody" is referred to herein with respect to the invention, it is normally understood that an antigen-binding portion thereof may also be used. An antigen-binding portion competes with the intact antibody for specific binding. See generally, Fundamental Immunology, Ch. 7 (Paul, W., ed., second ed. Raven Press, N.Y. (1989)) (incorporated by reference in its entirety for all purposes). Antigen-binding portions may be produced byrecombinant DNA techniques or by enzymatic or chemical cleavage of intact antibodies. In some embodiments, antigen-binding portions include Fab, Fab', F(ab')2, Fd, Fv, dAb, and complementarity determining region (CDR) fragments, single-chain antibodies or minibodies (scFv), chimeric antibodies, diabodies, nanobodies and any polypeptides that contain at least a portion of an antibody that is sufficient to confer specific antigen binding to the polypeptide.From N-terminus to C-terminus, both the mature light and heavy chain variable domains comprise the regions FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. The assignment of amino acids to each domain herein is in accordance with the definitions of IMGT convention described in Lefranc et al. (2003), Developmental & Comparative Immunology 27.1 (2003): 55-77.As used herein, a Fd fragment means an antibody fragment that consists of the VH and CH 1 domains; an Fv fragment consists of the VK or VL and VH domains of a single arm of an antibody; and a dAb fragment (Ward et al, Nature 341 :544-546 (1989)) consists of a VH domain.In some embodiments, the antibody is monoclonal antibody, a single-chain antibody (scFv) or minibody in which a VL and VH domains are paired to form a monovalent molecule via a synthetic linker that enables them to be made as a single protein chain. (Bird et al, Science 242:423-426 (1988) and Huston et al, Proc. Natl Acad. ScL USA 85:5879-5883 (1988)). Preferably such VL and VH domains are human sequences.In some embodiments, the antibodies are diabodies, i.e., are bivalent antibodies in which VH and VL or VK domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen binding sites. (See e.g., Holliger P. et al, Proc. Natl. Acad. ScL USA 90:6444-6448 (1993), and Poljak R. J. et al, Structure 2: 1121-1123 (1994)). In such embodiments, the CDR(s) may be incorporated as part of a larger polypeptide chain, may be covalently linked to another polypeptide chain, or may be incorporated noncovalently. In embodiments having one or more binding sites, the binding sites may be identical to one another or may be different.In certain preferred aspects of the invention, a monoclonal antibody according to any of the embodiments disclosed in the present specification and in the claims is a human antibody, i.e., a human monoclonal antibody, or an antigen-binding portion thereof.As used herein, the term "human antibody" means any antibody in which the variable and constant domain sequences are human sequences or any of the CDRs of the variable domain sequences are human sequences. The term encompasses antibodies with sequences derived from human genes, but which have been changed, e.g. to decrease possible immunogenicity, increase affinity, eliminate cysteines that might cause undesirable folding, etc. The term encompasses such antibodies produced recombinantly in non-human cells, which might impart glycosylation not typical of human cells. The term "chimeric antibody" as used herein means an antibody that comprises regions from two or more different antibodies.The term "epitope" includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor or otherwise interacting with a molecule. Epitopes or antigenic determinants generally consist of chemically active surface groupings of molecules such as amino acids or carbohydrate or sugar side chains and generally have specific three- dimensional structural characteristics, as well as specific charge characteristics.An epitope may be "linear" or "conformational." In a linear epitope, all of the points of interaction between the protein and the interacting molecule (such as an antibody) occur linearly along the primary amino acid sequence of the protein. In a conformational epitope, the points of interaction occur across amino acid residues on the protein that are separated from one another.An antibody is said to specifically bind an antigen when the dissociation constant is for example < 1 mM, preferably < 100 nM and most preferably < 10 nM, even more preferably < 1 nM. The dissociation constant may be measured by any of the methods available in the state of the art as for example using enzyme-linked immunoabsorbent assay (ELISAs), radioimmunoassays (RIAs), flow cytometry, surface plasmon resonance, such as BIACORE(TM).For example, the expression “specifically binds to a methylated ERG protein” as herein means that the antibody or its antigen-binding portion preferably binds to said methylated ERG protein with an affinity constant (KD) of equal to or less than about 1 nM as measured by surface plasmon resonance (SPR) , the antibody binds preferably .The term "polynucleotide" as referred to herein means a polymeric form of nucleotides of at least 10 bases in length, either ribonucleotides or deoxyribonucleotides or a modified form of either type of nucleotide. The term includes single and double stranded forms.The term "isolated polynucleotide" or “isolated nucleic acid molecule” as used herein means a polynucleotide of genomic, cDNA, or synthetic origin or some combination thereof, which by virtue of its origin the "isolated polynucleotide" (1) is not associated with all or a portion of a polynucleotides with which the "isolated polynucleotide" is found in nature, (2) is operably linked to a polynucleotide to which it is not linked in nature, or (3) does not occur in nature as part of a larger sequence.The term "naturally occurring nucleotides" as used herein includes deoxyribonucleotides and ribonucleotides. The term "modified nucleotides" as used herein includes nucleotides with modified or substituted sugar groups and the like. The term "oligonucleotide linkages" referred to herein includes oligonucleotides linkages such as phosphorothioate, phosphorodithioate, phosphoroselenoate, phosphorodiselenoate, phosphoroanilothioate, phoshoraniladate, phosphoroamidate, and the like. See e.g., LaPlanche et al., Nucl. Acids Res. 14:9081 (1986); Stec et al, J. Am. Chem. Soc. 106:6077 (1984); Stein et al., Nucl. Acids Res. 16:3209 (1988); Zon et al., Anti-Cancer Drug Design 6:539 (1991); Zon et al.. Oligonucleotides and Analogues: A Practical Approach, pp. 87-108 (F. Eckstein, Ed., Oxford University Press, Oxford England (1991)); U.S. Patent No. 5,151,510; Uhlmann and Peyman, Chemical Reviews 90:543 (1990), the disclosures of which are hereby incorporated by reference. An oligonucleotide can include a label for detection, if desired."Operably linked" sequences include both expression control sequences that are contiguous with the gene of interest and expression control sequences that act in trans or at a distance to control the gene of interest.The term "expression control sequence" as used herein means polynucleotide sequences that are necessary to affect the expression and processing of coding sequences to which they are ligated. Expression control sequences include appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (i.e., Kozak consensus sequence); sequences that enhance protein stability; and when desired, sequences that enhance protein secretion. The nature of such control sequences differs depending upon the host organism; in prokaryotes, such control sequences generally include promoter, ribosomal binding site, and transcription termination sequence; in eukaryotes, generally, such control sequences include promoters and transcription termination sequence.The term "control sequences" is intended to include, at a minimum, all components whose presence is essential for expression and processing, and can also include additional components whose presence is advantageous, for example, leader sequences and fusion partner sequences.Unless otherwise defined, the polynucleotide or nucleic acid molecules according to any of the variants disclosed in the present specification and in the claims can be either DNA or RNA molecules.The term "vector", as used herein, means a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. In some embodiments, the vector is a plasmid, i.e., a circular double stranded piece of DNA into which additional DNA segments may be ligated. In some embodiments, the vector is a viral vector, wherein additional DNA segments may be ligated into the viral genome. In some embodiments, the vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). In other embodiments, the vectors (e.g., non-episomal mammalian vectors) can be integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as "recombinant expression vectors" (or simply, "expression vectors").The term "recombinant host cell" (or simply "host cell"), as used herein, means a cell into which a recombinant expression vector has been introduced. It should be understood that "recombinant host cell" and "host cell" mean not only the particular subject cell but also the progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term "host cell" as used herein.The term "percent sequence identity" in the context of nucleotide or aminoacidic sequences means the residues in two sequences that are the same when aligned for maximum correspondence. The length of sequence identity comparison may be over a stretch of at least about nine nucleotides, usually at least about 18 nucleotides, more usually at least about 24 nucleotides, typically at least about 28 nucleotides, more typically at least about 32 nucleotides, and preferably at least about 36, 48 or more nucleotides. There are a number ofdifferent algorithms known in the art which can be used to measure nucleotide sequence identity. For instance, polynucleotide sequences can be compared using FASTA, Gap or Bestfit, which are programs available, provides alignments and percent sequence identity of the regions of the best overlap between the query and search sequences (Pearson, Methods Enzymol. 183:63-98 (1990); Pearson, Methods Mol. Biol. 132: 185-219 (2000); Pearson, Methods Enzymol. 266:227-258 (1996); Pearson, J Mol. Biol 276:71-84 (1998); incorporated herein by reference).The term "substantial similarity" or "substantial sequence similarity," when referring to a nucleic acid or fragment thereof, or aminoacidic means that when optimally aligned with appropriate nucleotide insertions or deletions with another nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 85%, preferably at least about 90%, and more preferably at least about 95%, 96%, 97%, 98% or 99% of the nucleotide bases, as measured by any well-known algorithm of sequence identity, such as FASTA, BLAST or Gap, as discussed above. As applied to polypeptides, the term "substantial identity" means that two peptide sequences, when optimally aligned, such as by the programs GAP or BESTFIT using default gap weights as supplied with the programs, share at least 70%, 75% or 80% sequence identity, preferably at least 90% or 95% sequence identity, and more preferably at least 97%, 98% or 99% sequence identity. In certain embodiments, residue positions that are not identical differ by conservative amino acid substitutions. A "conservative amino acid substitution" is one in which an amino acid residue is substituted by another amino acid residue having a side chain R group with similar chemical properties (e.g., charge or hydrophobicity). In general, a conservative amino acid substitution will not substantially change the functional properties of a protein. In cases where two or more amino acid sequences differ from each other by conservative substitutions, the percent sequence identity may be adjusted upwards to correct for the conservative nature of the substitution. Means for making this adjustment are well-known to those of skill in the art. See, e.g., Pearson, Methods Mol. Biol. 243:307-31 (1994). Examples of groups of amino acids that have side chains with similar chemical properties include 1) aliphatic side chains: glycine, alanine, valine, leucine, and isoleucine; 2) aliphatic-hydroxyl side chains: serine and threonine; 3) amide-containing side chains: asparagine and glutamine; 4) aromatic side chains: phenylalanine, tyrosine, and tryptophan; 5) basic side chains: lysine, arginine, and histidine; 6) acidic side chains: aspartic acid and glutamic acid;and 7) sulphur-containing side chains: cysteine and methionine. Conservative amino acids substitution groups are: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, glutamate-aspartate, and asparagine-glutamine. Alternatively, a conservative replacement is any change having a positive value in the PAM250 log-likelihood matrix disclosed in Gonnet et al, Science 256: 1443-45 (1992), incorporated herein by reference. A "moderately conservative" replacement is any change having a nonnegative value in the PAM250 log-likelihood matrix. Sequence identity for polypeptides is typically measured using sequence analysis software. Protein analysis software matches sequences using measures of similarity assigned to various substitutions, deletions and other modifications, including conservative amino acid substitutions. For instance, GCG contains programs such as "Gap" and "Bestfit" which can be used with default parameters as specified by the programs to determine sequence homology or sequence identity between closely related polypeptides, such as homologous polypeptides from different species of organisms or between a wild type protein and a mutein thereof.As used herein, the terms "label" or "labelled" refers to incorporation of another molecule in the antibody. In one embodiment, the label is a detectable marker, e.g., incorporation of a radiolabelled amino acid or attachment to a polypeptide of biotinyl moieties that can be detected by marked avidin (e.g., streptavidin containing a fluorescent marker or enzymatic activity that can be detected by optical or colorimetric methods). In another embodiment, the label or marker can be therapeutic, e.g., a drug conjugate or toxin. Various methods of labelling polypeptides and glycoproteins are known in the art and may be used.Anti-methylated ERG protein Antibodies and Characterization ThereofIn one embodiment, the invention provides an antibody or antigen-binding portion thereof capable of specifically binding to a methylated ERG protein (mERG). In one embodiment, the invention provides an antibody or antigen-binding portion thereof capable of specifically binding to an epitope of said methylated ERG protein comprising a methylated lysine residue. In particular, said epitope of the methylated ERG protein does not include methylated residues other than said methylated lysine residue.In one preferred embodiment, the invention provides an antibody or antigen binding portion thereof capable of specifically binding to an epitope of said methylated ERG protein, whichepitope comprises a methylated lysine residue corresponding to residue K362 of said ERG protein.In one embodiment, said methylated lysine residue is selected from a mono-methylated lysine residue (i.e. 6-N-methyllysine), a bi-methylated lysine residue and a tri-methylated lysine residue, preferably said methylated lysine residue is a mono-methylated lysine residue.In certain preferred aspects, the invention provides an antibody or antigen-binding portion thereof that is capable of specifically binding to an epitope of said methylated ERG protein, which epitope comprises a mono-methylated lysine residue, while is not able of specifically binding to an epitope of said methylated ERG protein comprising a bi-methylated or trimethylated lysine residue.In one embodiment, the invention provides an antibody or antigen binding portion thereof capable of specifically binding to an epitope of said methylated ERG protein, which epitope comprises a sequence ranging from position 356 to position 369 of said ERG protein, in particular wherein said position is determined with reference to the sequence of wild type human ERG protein set forth in SEQ ID No 1.In particular, whenever reference to “R356”, “Y369”, and “K362” is mentioned in the present specification and in the claims, this refers to the arginine (abbreviated with letter W), tyrosine (abbreviated with letter Y) and lysine (abbreviated with the letter K) residues, respectively at positions 356, 369, and 362 as determined with reference to the aminoacidic sequence of the wild-type human ERG protein set forth in SEQ ID No 1.Preferably, the epitope of said methylated ERG protein according to any of the variants disclosed herein is a peptide comprising or consisting of an aminoacidic sequence selected from the group consisting of:RRWGER[MetK]SKPNMNY (SEQ ID No. 2):RWGER[MetK]SKPNMN (SEQ ID No. 3);WGER[MetK]SKPNM (SEQ ID No. 4);WGER[MetK]SKPN (SEQ ID No. 5):GER[MetK]SKPNM (SEQ ID No. 6); andGER[MetK]SKPN (SEQ ID No. 7),wherein the symbol “[MetK]” indicates a methylated lysine residue, preferably a monomethylated lysine residue (i.e. 6-N-Methyllysine), in particular wherein said MetK residue is the lysine residue at position 362 as determined with reference to the aminoacidic sequence of the wild-type human ERG protein set forth in SEQ ID No 1.Most preferably, the epitope is a peptide comprising or consisting of the following aminoacidic sequence:RRWGER[MetK]SKPNMNY (SEQ ID No. 2).In certain aspects, the antibody or antigen-binding portion thereof according to any of the embodiments disclosed in the present specification and in the claims is selected from a monoclonal antibody, a minibody, a multi-specific antibody, a bi-specific antibody, a three- specific antibody, a scFV, a diabody, a triabody, a tetrabody, a linear antibody, a chelating recombinant antibody, a tribody, a bibody, an intrabody, a nanobody, an antibody-drug conjugate, a binding-domain immunoglobulin fusion protein, a fusion antibody, an immunoadhesin, or an antigen binding fragment thereof, preferably is selected from a monoclonal antibody and a minibody,In certain aspects, said antibody or antigen binding portion thereof is a monoclonal antibody or an antigen-binding portion thereof comprising a heavy chain variable domain (VH) having the amino acid sequence set forth in SEQ ID No. 8 and a light chain variable domain (VL) amino acid sequence set forth in SEQ ID No:9. Said monoclonal antibody is indicated throughout the present specification also as “13H2-1”.In certain aspects, the invention provides an antibody that comprises a heavy chain variable domain (VH) encoded by the nucleotide sequence set forth in SEQ ID No.10 and a light chain variable domain (VL) that is encoded by the nucleotide sequence set forth in SEQ ID No. 11.In certain aspects, the invention provides an antibody or antigen-binding portion thereof that is capable of specifically binding to a methylated ERG protein and comprising VL and VH domains that are at least 85%, 90%, 95%, 97%, 98% or 99% identical in amino acid sequence to the VL and VH domains, respectively, of a monoclonal antibody herein denoted as 13H2- 1.In certain aspects, the invention provides an antibody or antigen-binding portion thereof that is capable of specifically binding to a methylated ERG protein comprising the light chain and the heavy chain that are at least 85%, 90%, 95%, 97%, 98% or 99% identical in aminoacid sequence to the light chain and the heavy chain, respectively, of a monoclonal antibody herein denoted as 13H2-1.Preferably, an antibody according to any of the embodiments disclosed in the present specification and in the claims is a human antibody or a human monoclonal antibody.In certain aspects, a monoclonal antibody or antigen binding portion thereof according to any of the embodiments disclosed in the present specification and in the claims specifically binds to an epitope of said methylated ERG protein according to any of the variants disclosed in the present specification and in the claims, and at least partially inhibits prostate tumor growth.One type of amino acid substitution that may be made is to change one or more cysteines in the antibody, which may be chemically reactive, to another residue, such as, without limitation, alanine, or serine. In one embodiment, there is a substitution of a non-canonical cysteine. The substitution can be made in a CDR or framework region of a variable domain or in the constant domain of an antibody. In some embodiments, the cysteine is canonical. Another type of amino acid substitution that may be made is to change any potential proteolytic sites in the antibody. Such sites may occur in a CDR or framework region of a variable domain or in the constant domain of an antibody. Substitution of cysteine residues and removal of proteolytic sites may decrease the risk of any heterogeneity in the antibody product and thus increase its homogeneity. Another type of amino acid substitution is to eliminate asparagine-glycine pairs, which form potential deamidation sites, by altering one or both of the residues. In some embodiments, the C-terminal lysine of the heavy chain of the anti-mERG antibody of the invention is cleaved. In various embodiments of the invention, the heavy and light chains of the anti-mERG protein antibodies may optionally include a signal sequence.The class and subclass of the antibodies according to the present invention may be determined by any method known in the art. In general, the class and subclass of an antibody may be determined using antibodies that are specific for a particular class and subclass of antibody. Such antibodies are commercially available. The class and subclass can be determined by ELISA, or Western blot (immunoblot) as well as other techniques. Alternatively, the class and subclass may be determined by sequencing all or a portion of the constant domains of the heavy and / or light chains of the antibodies, comparing their aminoacid sequences to the known amino acid sequences of various class and subclasses of immunoglobulins, and determining the class and subclass of the antibodies.In some embodiments, the antibody according to any of the embodiments disclosed herein is an IgG, an IgM, an IgE, an IgA, or an IgD molecule. In one embodiment, the antibody is an IgG and is an IgGl, IgG2, IgG3, IgG4 subclass. In still another embodiment, the human antibody subclass is IgGl.In some embodiments of the invention, the antibodies according to any of the embodiments disclosed herein bind to a methylated ERG protein or epitope thereof according to any of the variants disclosed herein, with high affinity. The binding affinity and dissociation rate of an antibody to methylated ERG proteins can be determined by methods known in the art. The binding affinity can be measured by ELISAs, RIAs, flow cytometry, surface plasmon resonance, such as BIACORE(TM). The dissociate rate can be measured by surface plasmon resonance. Preferably, the binding affinity and dissociation rate is measured by surface plasmon resonance. One can determine whether an antibody has substantially the same KD as an anti-mERG antibody by using methods known in the art.In particular, an antibody or antigen binding portion thereof according to any of the variants disclosed herein specifically binds to said methylated ERG protein with an affinity constant (KD) of equal to or less than about 1 nM as measured by surface plasmon resonance (SPR).The invention further provides a monoclonal antibody that binds to said methylated ERG protein or epitopes thereof according to any of the variants disclosed herein and competes or cross-competes with and / or binds the same epitope as an antibody herein denoted as 13H2- 1. If two antibodies reciprocally compete with each other for binding to said methylated ERG protein, they are said to cross-compete.One can determine whether an antibody binds to the same epitope or cross competes for binding with an anti-mERG antibody according to the present invention by using methods known in the art. In one embodiment, one allows the antibody of the invention to bind to mERG-protein under saturating conditions and then measures the ability of the test antibody to bind to the mERG protein. If the test antibody is able to bind to the mERG protein at the same time as the antibody of the present invention, then the test antibody binds to a different epitope as the antibody of the invention. However, if the test antibody is not able to bind tomERG protein at the same time, then the test antibody binds to the same epitope, an overlapping epitope, or an epitope that is in close proximity to the epitope bound by the antibody according to the present invention, or the binding of the antibody according to the present invention may induce a conformational change in the mERG protein that prevents or reduces binding of the test antibody. This experiment can be performed using ELISA, RIA, BIACORE(TM), flow cytometry or other methods known in the art.To test whether an antibody according to the present invention cross-competes with another antibody capable of binding to the mERG protein according to any of the variants disclosed herein, one may use the competition method described above in two directions i.e. determining if the reference antibody blocks the test antibody and vice versa. In one embodiment, the experiment is performed using ELISA. Methods of determining KD are discussed further below.As will be further detailed below, according to a preferred embodiment, the invention provides for an antibody or antigen binding portion thereof that is capable of specifically binding to a methylated ERG protein, in particular to an epitope of said methylated ERG protein according to any of the variants disclosed herein, which antibody or antigen binding portion thereof is a minibody herein denoted as scFv-13H2-l .Nucleic Acids, Vectors, Host Cells, and Recombinant Methods of Making Antibodies Nucleic AcidsThe present invention also encompasses isolated nucleic acid molecules encoding antibodies or antigen-binding portions thereof according to any of the embodiments disclosed herein. An isolated nucleic acid molecule according to any of the embodiments disclosed in the present specification and in the claims can be a DNA or RNA molecule, in particular is a mRNA.In some embodiments, different nucleic acid molecules encode a heavy chain and a light chain of an antibody according to the present invention. In other embodiments, the same nucleic acid molecule encodes a heavy chain and a light chain of an antibody according to the present invention.In one embodiment, the nucleic acid encodes an antibody, or antigen-binding portion thereof, of the invention. In some embodiments, the nucleic acid molecule comprises a nucleotide sequence that encodes a VL amino acid sequence comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10conservative amino acid substitutions and / or 1, 2, or 3 non- conservative substitutions compared to germline. Substitutions may be in the CDR regions, the framework regions, or in the constant domain. In some embodiments, the nucleic acid molecule encodes a VL amino acid sequence comprising one or more variants compared to germline sequence that are identical to the variations found in the VL of the antibody herein denoted as 13H2-1. In some embodiments, the nucleic acid molecule encodes at least three amino acid substitutions compared to the germline sequence found in the VL of the antibody herein denoted as 13H2-1.In some embodiments, the nucleic acid molecule comprises a nucleotide sequence that encodes the VL amino acid sequence of the antibody herein denoted as 13H2-1 or a variant or portion thereof. In some embodiments, the nucleic acid encodes an amino acid sequence comprising the light chain CDRs of the antibody herein denoted as 13H2-1. In some embodiments, said portion is a contiguous portion comprising CDR1-CDR3. In some embodiments, the nucleic acid encodes the amino acid sequence of the light chain CDRs of said antibody. In some embodiments, said portion encodes a contiguous region from CDR1- CDR3 of the light chain of an antibody according to the present invention.In some embodiments, the nucleic acid molecule encodes a VL amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98% or 99% identical to a VL amino acid sequence of a VL region of the antibody herein denoted as 13H2-1. Nucleic acid molecules of the invention include nucleic acids that hybridize under highly stringent conditions, such as those described above, to a nucleotide sequence encoding the amino acid sequence of a VL region.In another embodiment, the nucleic acid encodes a full-length light chain of the antibody herein denoted as 13H2-1 or a light chain comprising a mutation, such as one disclosed herein.In still another embodiment, the nucleic acid molecule encodes the variable domain of the heavy chain (VH) that comprises a human VH1, VH3 or VH4 family gene sequence or a sequence derived therefrom. In some embodiments, the nucleic acid molecule encodes one or more amino acid mutations compared to the germline sequence that are identical to amino acid mutations found in the VH of the antibody herein denoted as 13H2-1.In some embodiments, the nucleic acid molecule comprises a nucleotide sequence that encodes at least a portion of the VH amino acid sequence of the antibody herein denoted as13H2-1, all three CDR regions, a contiguous portion including CDR1 -CDR3, or the entire VH region, with or without a signal sequence. In some embodiments, the nucleic acid molecule comprises a nucleotide sequence that encodes the amino acid sequence of one of the antibody herein denoted as 13H2-1, or said sequence lacking the signal sequence. In some preferred embodiments, the nucleic acid molecule comprises at least a portion of the nucleotide sequence of the antibody herein denoted as 13H2-1, or said sequence lacking the signal sequence. In some embodiments, said portion encodes the VH region (with or without a signal sequence), a CDR3 region, all three CDR regions, or a contiguous region including CDR1-CDR3.In some embodiments, the nucleic acid molecule encodes a VH amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98% or 99% identical to the VH amino acid sequences of the antibody herein denoted as 13H2-1.Nucleic acid molecules of the invention include nucleic acids that hybridize under highly stringent conditions, such as those described above, to a nucleotide sequence encoding the amino acid sequence of the antibody herein denoted as 13H2-lor that encodes a VH region thereof.In another embodiment, the nucleic acid encodes a full-length heavy chain of the antibody herein denoted as 13H2-1, or a heavy chain having the amino acid sequence of the antibody herein denoted as 13H2-1 with or without a signal sequence, or a heavy chain comprising a mutation, such as one of the variants discussed herein. Further, the nucleic acid may comprise the nucleotide sequence of the antibody herein denoted as 13H2-1, with or without a signal sequence, or a nucleic acid molecule encoding a heavy chain comprising a mutation, such as one of the variants discussed herein.A nucleic acid molecule encoding the heavy or light chain of an antibody or portions thereof according to the invention can be isolated from any source that produces such antibody.In various embodiments, the nucleic acid molecules are isolated from hybridoma cell lines. Methods of isolating mRNA encoding an antibody are well known in the art. See, e.g., Sambrook et al. The mRNA may be used to produce cDNA for use in the polymerase chain reaction (PCR) or cDNA cloning of antibody genes. In one embodiment, the nucleic acid molecule is isolated from a hybridoma that has as one of its fusion partners a human immunoglobulin-producing cell from a non-human transgenic animal. In an even more preferred embodiment, the human immunoglobulin producing cell is isolated from aXENOMOUSE animal. In another embodiment, the human immunoglobulin-producing cell is from a non-human, non-mouse transgenic animal, as described above. In another embodiment, the nucleic acid is isolated from a non-human, non-transgenic animal. The nucleic acid molecules isolated from a non-human, non-transgenic animal may be used, e.g., for humanized antibodies. In some embodiments, a nucleic acid encoding a heavy chain of an antibody of the invention can comprise a nucleotide sequence encoding a VH domain of the invention joined in-frame to a nucleotide sequence encoding a heavy chain constant domain from any source. Similarly, a nucleic acid molecule encoding a light chain of an antibody of the invention can comprise a nucleotide sequence encoding a VL domain of the invention joined in-frame to a nucleotide sequence encoding a light chain constant domain from any source. In a further aspect of the invention, nucleic acid molecules encoding the variable domain of the heavy (VH) and / or light (VL or VK) chains are "converted" to full- length antibody genes. In one embodiment, nucleic acid molecules encoding the VH or VL or VK domains are converted to full-length antibody genes by insertion into an expression vector already encoding heavy chain constant (CH) or light chain constant (CL) domains, respectively, such that the VH segment is operatively linked to the CH segment(s) within the vector, and / or the VL or VK segment is operatively linked to the CL segment within the vector. In another embodiment, nucleic acid molecules encoding the VH and / or VL or VK domains are converted into full-length antibody genes by linking, e.g., ligating, a nucleic acid molecule encoding a VH and / or VL or VK domains to a nucleic acid molecule encoding a CH and / or CL domain using standard molecular biological techniques. Nucleotide sequences of human heavy and light chain immunoglobulin constant domain genes are known in the art. See, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed., NIH Publ. No. 91-3242, 1991. Nucleic acid molecules encoding the full-length heavy and / or light chains may then be expressed from a cell into which they have been introduced and the antibody isolated.The nucleic acid molecules may be used to recombinantly express large quantities of antibodies of the invention. The nucleic acid molecules also may be used to produce chimeric antibodies, bispecific antibodies, single chain antibodies, immunoadhesins, diabodies, mutated antibodies and antibody derivatives, especially minibodies as described further below. If the nucleic acid molecules are derived from a non-human, non-transgenic animal, the nucleic acid molecules may be used for antibody humanization, also as described below.In another embodiment, a nucleic acid molecule of the invention is used as a probe or PCR primer for a specific antibody sequence. For instance, the nucleic acid can be used as a probe in diagnostic methods or as a PCR primer to amplify regions of DNA that could be used, inter alia, to isolate additional nucleic acid molecules encoding variable domains of the antibodies. In some embodiments, the nucleic acid molecules are oligonucleotides. In some embodiments, the oligonucleotides are from highly variable domains of the heavy and light chains of the antibody of interest. In some embodiments, the oligonucleotides encode all or a part of one or more of the CDRs of the antibody herein denoted as 13H2-1 or variants thereof as described herein.According to one preferred embodiment, the invention provides for an isolated nucleic acid molecule that comprises or consists of one or more sequences selected from SEQ ID No. 10 and SEQ ID No. 11.According to another embodiment, the invention provides for an isolated nucleic acid molecule that comprises or consists of the sequence set forth in SEQ ID No. 12.VectorsThe invention provides vectors comprising nucleic acid molecules that encode an antibody or antigen binding portion thereof, according to any of the variants disclosed in the present specification and in the claims. In one embodiment, the vector comprises a nuclei acid molecule that encodes for the heavy chain of an antibody of the invention or an antigenbinding portion thereof. The invention also provides vectors comprising nucleic acid molecules that encode the light chain of such antibodies or antigen-binding portion thereof. The invention further provides vectors comprising nucleic acid molecules encoding fusion proteins, modified antibodies, antibody fragments, minibodies and probes thereof. In some embodiments, the antibodies or antigen-binding portions of the invention are expressed by inserting DNAs encoding partial or full-length light and heavy chains, obtained as described above, into expression vectors such that the genes are operatively linked to necessary expression control sequences such as transcriptional and translational control sequences. Expression vectors include plasmids, retroviruses, adenoviruses, adeno-associated viruses (AAV), plant viruses such as cauliflower mosaic virus, tobacco mosaic virus, cosmids, YACs, EBV derived episomes, and the like. The antibody gene is ligated into a vector suchthat transcriptional and translational control sequences within the vector serve their intended function of regulating the transcription and translation of the antibody gene. The expression vector and expression control sequences are chosen to be compatible with the expression host cell used. The antibody light chain gene and the antibody heavy chain gene can be inserted into separate vectors. In one embodiment, both genes are inserted into the same expression vector. The antibody genes are inserted into the expression vector by standard methods (e.g., ligation of complementary restriction sites on the antibody gene fragment and vector, or blunt end ligation if no restriction sites are present). A convenient vector is one that encodes a functionally complete human CH or CL immunoglobulin sequence, with appropriate restriction sites engineered so that any VH or VL or VK sequence can easily be inserted and expressed, as described above. In such vectors, splicing usually occurs between the splice donor site in the inserted J region and the splice acceptor site preceding the human C domain, and also at the splice regions that occur within the human CH exons. Polyadenylation and transcription termination occur at native chromosomal sites downstream of the coding regions. The recombinant expression vector also can encode a signal peptide that facilitates secretion of the antibody chain from a host cell. The antibody chain gene may be cloned into the vector such that the signal peptide is linked in-frame to the amino terminus of the immunoglobulin chain. The signal peptide can be an immunoglobulin signal peptide or a heterologous signal peptide (i.e. a signal peptide from a non-immunoglobulin protein). In addition to the antibody chain genes, the recombinant expression vectors of the invention carry regulatory sequences that control the expression of the antibody chain genes in a host cell. It will be appreciated by those skilled in the art that the design of the expression vector, including the selection of regulatory sequences may depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. Preferred regulatory sequences for mammalian host cell expression include viral elements that direct high levels of protein expression in mammalian cells, such as promoters and / or enhancers derived from retroviral LTRs, cytomegalovirus (CMV) (such as the CMV promoter / enhancer), Simian Virus 40 (SV40) (such as the SV40 promoter / enhancer), adenovirus, (e.g. the adenovirus major late promoter (AdMLP)), polyoma and strong mammalian promoters such as native immunoglobulin and actin promoters. For further description of viral regulatory elements, and sequences thereof, see e.g., U.S. Patent No. 5,168,062, U.S. Patent No. 4,510,245 and U.S. Patent No. 4,968,615.Methods for expressing antibodies in plants, including a description of promoters and vectors, as well as transformation of plants is known in the art. See, e.g., United States Patent 6,517,529, incorporated herein by reference. Methods of expressing polypeptides in bacterial cells or fungal cells, e.g., yeast cells, are also well known in the art. In addition to the antibody chain genes and regulatory sequences, the recombinant expression vectors of the invention may carry additional sequences, such as sequences that regulate replication of the vector in host cells (e.g., origins of replication) and selectable marker genes. The selectable marker gene facilitates selection of host cells into which the vector has been introduced (see e.g., U.S. Patent Nos. 4,399,216, 4,634,665 and 5,179,017, incorporated herein by reference). For example, typically the selectable marker gene confers resistance to drugs, such as G418, hygromycin or methotrexate, on a host cell into which the vector has been introduced. Preferred selectable marker genes include the dihydrofolate reductase (DHFR) gene (for use in dhfr- host cells with methotrexate selection / amplification), the neo gene (for G418 selection), and the glutamate synthetase gene.Non-Hybridoma Host Cells and Methods of Recombinantly Producing ProteinNucleic acid molecules encoding antibodies and vectors according to the present invention comprising these nucleic acid molecules can be used for transfection or transformation of a suitable mammalian, plant, bacterial or yeast host cell. Transfection or transformation can be by any known method for introducing polynucleotides into a host cell. Methods for introduction of heterologous polynucleotides into mammalian cells are well known in the art and include dextran-mediated transfection, calcium phosphate precipitation, polybrene- mediated transfection, protoplast fusion, electroporation, encapsulation of the polynucleotide(s) in liposomes, and direct microinjection of the DNA into nuclei. In addition, nucleic acid molecules may be introduced into mammalian cells by viral vectors. Methods of transforming cells are well known in the art (see, e.g., U.S. Patent Nos. 4,399,216, 4,912,040, 4,740,461, and 4,959,455, incorporated herein by reference). Methods for transforming plant cells are well known in the art, including, e.g., Agrob acterium- mediated transformation, biolistic transformation, direct injection, electroporation and viral transformation. Methods for transforming bacterial and yeast cells are also well known in the art. Mammalian cell lines available as hosts for expression are well known in the art and include many immortalized cell lines available from the American Type Culture Collection(ATCC). These include, inter alia, Chinese hamster ovary (CHO) cells, N50 cells, SP2 cells, HEK-293T cells, NIH-3T3 cells, HeLa cells, baby hamster kidney (BHK) cells, African green monkey kidney cells (COS), human hepatocellular carcinoma cells (e.g., Hep G2), A549 cells, and a number of other cell lines. Cell lines of particular preference are selected through determining which cell lines have high expression levels. Other cell lines that may be used are insect cell lines, such as Sf9 or Sf21 cells. When recombinant expression vectors encoding antibody genes are introduced into mammalian host cells, the antibodies are produced by culturing the host cells for a period of time sufficient to allow for expression of the antibody in the host cells or, more preferably, secretion of the antibody into the culture medium in which the host cells are grown. Antibodies can be recovered from the culture medium using standard protein purification methods. Plant host cells include, e.g., Nicotiana, Arabidopsis, duckweed, corn, wheat, potato, etc. Bacterial host cells include E. coli and Streptomyces species. Yeast host cells include Schizosaccharomyces pombe, Saccharomyces cerevisiae and Pichia pastoris. Further, expression of antibodies of the invention from production cell lines can be enhanced using a number of known techniques. For example, the glutamine synthetase gene expression system (the GS system) is a common approach for enhancing expression under certain conditions. The GS system is discussed in whole or part in connection with European Patent Nos. 0 216 846, 0256 055, 0 323 997 and 0338 841. It is likely that antibodies expressed by different cell lines or in transgenic animals will have different glycosylation from each other. However, all antibodies encoded by the nucleic acid molecules provided herein, or comprising the amino acid sequences provided herein are part of the instant invention, regardless of the glycosylation of the antibodies.Transgenic Animals and PlantsAntibodies of the invention also can be produced transgenically through the generation of a mammal or plant that is transgenic for the immunoglobulin heavy and light chain sequences of interest and production of the antibody in a recoverable form therefrom. In connection with the transgenic production in mammals, antibodies of the invention can be produced in, and recovered from, the milk of goats, cows, or other mammals. See, e.g., U.S. Patent Nos. 5,827,690, 5,756,687, 5,750,172, and 5,741,957, incorporated herein by reference. In some embodiments, non- human transgenic animals that comprise human immunoglobulin loci are immunized with methylated ERG proteins or portions thereof, such as a peptideaccording to any of the variants disclosed herein or an immunogenic portion thereof, as described above. Methods for making antibodies in plants are described, e.g., in U.S. patents 6,046,037 and 5,959,177, incorporated herein by reference.In some embodiments, non-human transgenic animals or plants are produced by introducing one or more nucleic acid molecules encoding an antibody of the invention into the animal or plant by standard transgenic techniques. See Hogan and United States Patent 6,417,429, supra. The transgenic cells used for making the transgenic animal can be embryonic stem cells or somatic cells or a fertilized egg. The transgenic non-human organisms can be chimeric, nonchimeric heterozygotes, and nonchimeric homozygotes. See, e.g., Hofian et al. Manipulating the Mouse Embryo: A Laboratory Manual second ed., Cold Spring Harbor Press (1999); Jackson et al, Mouse Genetics and Transgenics: A Practical Approach, Oxford University Press (2000); and Pinkert, Transgenic Animal Technology: A Laboratory Handbook, Academic Press (1999), all incorporated herein by reference. In some embodiments, the transgenic non-human animals have a targeted disruption and replacement by a targeting construct that encodes a heavy chain and / or a light chain of interest. In one embodiment, the transgenic animals comprise and express nucleic acid molecules encoding heavy and light chains that specifically bind to a methylated ERG protein epitope according to any of the variants disclosed herein.In some embodiments, the transgenic animals comprise nucleic acid molecules encoding a modified antibody such as a single-chain antibody, a minibody, a chimeric antibody or a humanized antibody. The antibodies of the invention may be made in any transgenic animal. In one embodiment, the non-human animals are mice, rats, sheep, pigs, goats, cattle or horses. The non-human transgenic animal expresses said encoded polypeptides in blood, milk, urine, saliva, tears, mucus and other bodily fluids.Class switchingAnother aspect of the invention provides a method for converting the class or subclass of an antibody of the invention to another class or subclass. In some embodiments, a nucleic acid molecule encoding a VL or VK or VH that does not include sequences encoding CL or CH is isolated using methods well-known in the art. The nucleic acid molecule then is operatively linked to a nucleotide sequence encoding a CL or CH from a desired immunoglobulin class or subclass. This can be achieved using a vector or nucleic acidmolecule that comprises a CL or CH chain, as described above. For example, an anti- mERG protein antibody that was originally IgM can be class switched to an IgG. Further, the class switching may be used to convert one IgG subclass to another, e.g., from IgGl to IgG2. Another method for producing an antibody of the invention comprising a desired isotype comprises the steps of isolating a nucleic acid encoding a heavy chain of an antibody of the invention and a nucleic acid encoding a light chain of an antibody of the invention, isolating the sequence encoding the VH region, ligating the VH sequence to a sequence encoding a heavy chain constant domain of the desired isotype, expressing the light chain gene and the heavy chain construct in a cell, and collecting the antibody with the desired isotype.Modified AntibodiesIn another embodiment, a fusion antibody or immunoadhesin may be made that comprises all or a portion of an antibody of the invention linked to another polypeptide. In one embodiment, only the variable domains of the antibody according to any of the embodiments disclosed herein are linked to the polypeptide. In still another embodiment, the VH domain of an antibody of the invention is linked to a first polypeptide, while the VK domain of an antibody of the invention is linked to a second polypeptide that associates with the first polypeptide in a manner such that the VH and VK domains can interact with one another to form an antigen binding site. In still another embodiment, the VH domain is separated from the VK domain by a linker such that the VH and VL domains can interact with one another (see below under Single Chain Antibodies). The VH-linker-VK antibody is then linked to the polypeptide of interest. The fusion antibody is useful for directing a polypeptide to a mERG-expressing cell or tissue, such as a cell or tissue expressing the mERG protein comprising the methylated lysine residue K362. The polypeptide may be a therapeutic agent, such as a toxin, chemokine or other regulatory protein, or may be a diagnostic agent, such as an enzyme that may be easily visualized, such as horseradish peroxidase. In addition, fusion antibodies can be created in which two (or more) single-chain antibodies are linked to one another. This is useful if one wants to create a divalent or polyvalent antibody on a single polypeptide chain, or if one wants to create a bispecific antibody or nanobody. To create a single chain antibody or minibody according to the present invention (scFv), the VH- and VL-encoding DNA fragments of an antibody according to any of the variants disclosed herein, and particularly of an antibody herein denoted as 13H2-1, are operativelylinked to another fragment encoding a flexible linker, e.g., encoding the amino acid sequence (GIy4 -Ser)3, such that the VH and VK sequences can be expressed as a contiguous singlechain protein, with the VK and VH domains joined by the flexible linker. See, e.g., Bird et al, Science 242:423-426 (1988); Huston et al, Proc. Natl. Acad. ScL USA 85:5879-5883 (1988); McCafferty et al., Nature 348:552-554 (1990).The single chain antibody may be monovalent, if only a single VH and VK are used, bivalent, if two VH and VK are used, or polyvalent, if more than two VH and VK are used. Bispecific or polyvalent antibodies may be generated that bind specifically the mERG protein according to any of the variants disclosed herein and to another molecule. Bispecific antibodies or antigen-binding fragments can be produced by a variety of methods including fusion of hybridomas or linking of Fab' fragments. See, e.g., Songsivilai & Lachmann, Clin. Exp. Immunol. 79: 315-321 (1990), Kostelny et al, J. Immunol. 148: 1547-1553 (1992). In addition, bispecific antibodies may be formed as "diabodies" or "Janusins". In some embodiments, the bispecific antibody binds to two different epitopes of the mERG protein. In some embodiments, the bispecific antibody has a first heavy chain and a first light chain from monoclonal antibody herein denoted as 13H2-1 and an additional antibody heavy chain and light chain. In some embodiments, the additional light chain and heavy chain also are from one of the above-identified monoclonal antibodies, but are different from the first heavy and light chains. In some embodiments, the modified antibodies described above are prepared using one or more of the variable domains or CDR regions from a monoclonal antibody provided herein.In one particular embodiment, the antibody is a minibody and more particularly is a scFV comprising the VH and VL sequences of an antibody herein denoted as 13H2-1. Said minibody is indicated throughout the present specification also as “scFV-13H2-l”. Preferably, said VH and VL sequences are operably linked to a sequence for the nuclear import or a nuclear localization signal sequence.In certain aspects, the invention provides a minibody that is encoded by the nucleotide sequence set forth in SEQ ID No. 12.Derivatized and Labelled AntibodiesAn antibody or antigen-binding portion of the invention can be derivatized or linked to another molecule (e.g., another peptide or protein). In general, the antibodies or portionthereof are derivatized such that the specific binding to the mERG protein is not affected adversely by the derivatization or labelling. Accordingly, the antibodies and antibody portions of the invention are intended to include both intact and modified forms of the antibodies described herein. For example, an antibody or antibody portion of the invention can be functionally linked (by chemical coupling, genetic fusion, noncovalent association or otherwise) to one or more other molecular entities, such as another antibody (e.g., a bispecific antibody or a diabody), a detection agent, a cytotoxic agent, a pharmaceutical agent, and / or a protein or peptide that can mediate association of the antibody or antibody portion with another molecule (such as a streptavidin core region or a polyhistidine tag). One type of derivatized antibody is produced by crosslinking two or more antibodies (of the same type or of different types, e.g., to create bispecific antibodies). Suitable crosslinkers include those that are heterobifunctional, having two distinctly reactive groups separated by an appropriate spacer (e.g., m-maleimidobenzoyl-N- hydroxysuccinimide ester) or homobifunctional {e.g., disuccinimidyl suberate). Such linkers are available from Pierce Chemical Company, Rockford, II.

[0179] , Another type of derivatized antibody is a labelled antibody. Useful detection agents with which an antibody or antigen-binding portion of the invention may be derivatized include fluorescent compounds, including fluorescein, fluorescein isothiocyanate, rhodamine, phycoerythrin, 5-dimethylamine-l- napthalenesulfonyl chloride, lanthanide phosphors and the like. An antibody can also be labelled with enzymes that are useful for detection, such as horseradish peroxidase, [beta]- galactosidase, luciferase, alkaline phosphatase, glucose oxidase and the like. When an antibody is labelled with a detectable enzyme, it is detected by adding additional reagents that the enzyme uses to produce a reaction product that can be discerned. For example, when the agent horseradish peroxidase is present, the addition of hydrogen peroxide and diaminobenzidine leads to a coloured reaction product, which is detectable. An antibody can also be labelled with biotin, and detected through indirect measurement of avidin or streptavidin binding. An antibody can also be labelled with a predetermined polypeptide epitope recognized by a secondary reporter (e.g., leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags). In some embodiments, labels are attached by spacer arms of various lengths to reduce potential steric hindrance. An antibody can also be labelled with a radiolabelled amino acid. The radiolabel can be used for both diagnostic and therapeutic purposes. For instance, the radiolabel can be used to detectmERG-protein-expressing cells or tumours, in particular cells or tumors expressing ERG proteins comprising the methylated lysine residue K362, by x-ray or other diagnostic techniques. Further, the radiolabel can be used therapeutically as a toxin for cancerous cells or tumours. In some embodiments, the antibody can be labelled with a paramagnetic, radioactive or florigenic ion that is detectable upon imaging. In some embodiments, the paramagnetic ion is chromium (III), manganese (II), iron (III), iron (II), cobalt (II), nickel (II), copper (II), neodymium (III), samarium (III), ytterbium (III), gadolinium (III), vanadium (II), terbium (III), dysprosium (III), holmium (III) or erbium (III). In other embodiments, the radioactive ion is iodine 123, technetium 99, indium 111, rhenium 188, rhenium 186, copper 67, iodine 131, yttrium90, iodine 125, astatine 211, and gallium 67. In other embodiments, the antibody of the invention is labelled with an X-ray imaging agent such as lanthanum (III), gold (III) lead (II) and bismuth (III).In one embodiment the invention is a nanoparticle, in particular a lipid nanoparticle, comprising the nucleic acid, such as a DNA or a mRNA, encoding the antibody or antigen binding portion thereof herein disclosed.Compositions and KitsThe invention relates to compositions comprising any of the antibodies or antigen binding portions thereof according to any of the embodiments disclosed herein, and / or any of the nucleic acid molecules and / or vectors according to any of the embodiments disclosed herein, and one or more pharmaceutical acceptable excipients and / or carriers.In certain embodiments, the composition may comprise one or more antibodies or a binding portion thereof of any of the preceding embodiments.In certain embodiments the one or more antibodies are in a composition comprising a pharmaceutically acceptable carrier. In another embodiment, one or more of the antagonist antibodies of the invention are administered in combination with one or more additional antagonistic antibodies that bind different epitopes on a mERG protein according to any of the variants disclosed herein. As used herein, "pharmaceutically acceptable carrier" means any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. Some examples of pharmaceutically acceptable carriers are water, saline, phosphate buffered saline, dextrose, glycerol, ethanol and the like, as well as combinations thereof. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols suchas mannitol, sorbitol, or sodium chloride in the composition. Additional examples of pharmaceutically acceptable substances are wetting agents or minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives or buffers, which enhance the shelf life or effectiveness of the antibody. The compositions of this invention may be in a variety of forms, for example, liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, tablets, pills, powders, liposomes and suppositories. The preferred form depends on the intended mode of administration and therapeutic application. Typical preferred compositions are in the form of injectable or infusible solutions, such as compositions similar to those used for passive immunization of humans. The preferred mode of administration is parenteral (e.g., intravenous, subcutaneous, intraperitoneal, intramuscular). In one embodiment, the antibody is administered by intravenous infusion or injection. In still another embodiment, the antibody is administered by intramuscular or subcutaneous injection. Therapeutic compositions are typically sterile and stable under the conditions of manufacture and storage. The composition can be formulated as a solution, microemulsion, dispersion, liposome, or other ordered structure suitable to high drug concentration. Sterile injectable solutions can be prepared by incorporating the antibody according to any of the embodiments of the invention in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze-drying that yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. The proper fluidity of a solution can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prolonged absorption of injectable compositions can be brought about by including in the composition an agent that delays absorption, for example, monostearate salts and gelatin. The antibodies of the present invention can be administered by a variety of methods known in the art, although for many therapeutic applications, the preferred route / mode of administration is subcutaneous, intramuscular, or intravenous infusion. As will be appreciated by the skilledartisan, the route and / or mode of administration will vary depending upon the desired results. Other modes of administration include intraperitoneal, intrabronchial, transmucosal, intraspinal, intrasynovial, intraaortic, intranasal, ocular, otic, topical and buccal. In certain embodiments, the active compound of the antibody compositions may be prepared with a carrier that will protect the antibody against rapid release, such as a controlled release formulation, including implants, transdermal patches, and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Many methods for the preparation of such formulations are patented or generally known to those skilled in the art. See, e.g., Sustained and Controlled Release Drug Delivery Systems (J. R. Robinson, ed., Marcel Dekker, Inc., New York, 1978). The invention also provides compositions suitable for administration by inhalation, which comprise one or more of any of the antibodies described herein. Any of the antibodies of the invention may be conveniently delivered to a subject in the form of an aerosol spray presentation from pressurized packs or from a nebuliser, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of e.g., gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch. Dellamary et al. (2004) J Control Release. ;95(3): 489-500 describes formulations for the pulmonary delivery of antibodies. The invention also provides compositions, suitable for administration through the oral mucosa, which comprise one or more of any of the antibodies described herein. Oral transmucosal delivery refers to the delivery of a delivery vehicle across a mucous membrane in the oral cavity, pharyngeal cavity, or esophagus, and may be contrasted, for example, with traditional oral delivery, in which absorption of a drug occurs in the intestine. Accordingly, routes of administration in which the antibodies are absorbed through the buccal, sublingual, gingival, pharyngeal, and / or esophageal mucosa are all encompassed within "oral transmucosal delivery," as that term is used herein. For administration through the transmucosal mucosa, any of the antibody of the invention may be formulated, for example, into chewing gums (see U.S. Pat No. 5,711,961) or buccal patches (see e.g. U.S. Patent No. 5,298,256). The invention also provides compositions suitable for administration throughthe vaginal mucosa, which comprise one or more of any of the antibodies described herein. The antibodies of the invention may be formulated into a vaginal suppository, foam, cream, tablet, capsule, ointment, or gel. In certain embodiments, the compositions comprising the antibodies are formulated with permeants appropriate to the transmucosal barrier to be permeated. Such penetrants are generally known in the art, and include, for example, for trans mucosal administration bile salts and fusidic acid derivatives. In certain embodiments, an antibody of the invention can be orally administered, for example, with an inert diluent or an assailable edible carrier. The compound (and other ingredients, if desired) can also be enclosed in a hard- or soft-shell gelatine capsule, compressed into tablets, or incorporated directly into the subject's diet. For oral therapeutic administration, the antibodies can be incorporated with excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. To administer a compound of the invention by other than parenteral administration, it may be necessary to coat the compound with, or co-administer the compound with, a material to prevent its inactivation. Additional active compounds also can be incorporated into the compositions. In certain embodiments, a neutralizing antibody of the invention is co-formulated with and / or co-administered with one or more additional therapeutic agents, particularly anti-viral agents. These therapeutic agents include, without limitation, antibodies that bind other targets, photosensitizers, androgen, oestrogen, nonsteroidal anti-inflammatory agents, antihypertensive agents, analgesic agents, antidepressants, antibiotics, anticancer agents, anaesthetics, antiemetics, anti-infectants, contraceptives, antidiabetic agents, steroids, antiallergy agents, chemotherapeutic agents, anti-migraine agents, agents for smoking cessation, anti-viral agents, immunosuppressants, thrombolytic agent, cholesterol-lowering agents and anti-obesity agents. Therapeutic agents also include peptide analogues that inhibit prostate cancer growth and / or progression. In certain specific embodiments, the therapeutic agent(s) that is co-formulated with and / or co-administered with an antibody of the invention is an antimicrobial agent. Antimicrobial agents include antibiotics (e.g. antibacterial), antiviral agents, antifungal agents, and anti-protozoan agents. Non-limiting examples of antimicrobial agents are sulfonamides, trimethoprim-sulfamethoxazole, quinolones, penicillins, and cephalosporins. The compositions of the invention may include a "therapeutically effective amount" or a "prophylactically effective amount" of an antibody or antigen-binding portion of the invention. A "therapeutically effective amount" refers to an amount effective, atdosages and for periods of time necessary, to achieve the desired therapeutic result. A therapeutically effective amount of the antibody or antibody portion may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the antibody or antibody portion to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of the antibody or antibody portion are outweighed by the therapeutically beneficial effects. A "prophylactically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount may be less than the therapeutically effective amount. Dosage regimens can be adjusted to provide the optimum desired response (e.g., a therapeutic or prophylactic response). For example, a single bolus can be administered, several divided doses can be administered over time or the dose can be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It is especially advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the mammalian subjects to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on (a) the unique characteristics of the antibody or portion thereof and the particular therapeutic or prophylactic effect to be achieved, and (b) the limitations inherent in the art of compounding such an antibody for the treatment of sensitivity in individuals. An exemplary, non-limiting range for a therapeutically or prophylactically- effective amount of an antibody or antibody portion of the invention is 0.025 to 50 mg / kg, more preferably 0.1 to 50 mg / kg, more preferably 0.1- 25, 0.1 to 10 or 0.1 to 3 mg / kg. In some embodiments, a formulation contains 5 mg / nil of antibody in a buffer of 20mM sodium citrate, pH 5.5, 140mM NaCl, and 0.2mg / ml polysorbate 80. It is to be noted that dosage values may vary with the type and severity of the condition to be alleviated. It is to be further understood that for any particular subject, specific dosage regimens should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions, and that dosage ranges set forth herein are exemplary only and are notintended to limit the scope or practice of the claimed composition. Another aspect of the present invention provides kits comprising an antibody, or antigen-binding portion, of the invention or a composition comprising such an antibody or antigen-binding fragment. A kit may include, in addition to the antibody or composition, diagnostic or therapeutic agents. A kit can also include instructions for use in a diagnostic or therapeutic method, as well as packaging material such as, but not limited to, ice, dry ice, styrofoam, foam, plastic, cellophane, shrink wrap, bubble wrap, cardboard and starch peanuts. In one embodiment, the kit includes the antibody or a composition comprising it and a diagnostic agent that can be used in a method described below. In still another embodiment, the kit includes the antibody or a composition comprising it and one or more therapeutic agents that can be used in a method described below.In one embodiment the antibodies or binding portion thereof, the nucleic acid molecules, the vectors or compositions comprising such antibodies, nucleic acid molecules or vectors according to any one of the embodiments herein disclosed are for use in a prophylactic and / or therapeutic treatment of a prostate cancer in a subject in need thereof, preferably wherein said cancer is a ERG fusion-positive prostate cancer.In some embodiments, the subject of treatment is a human. In other embodiments, the subject is a veterinary subject.The use of such antibodies and compositions of said antibodies include, but are not limited to, immunization in persons at risk of having prostate cancer, in particular ERG fusionpositive prostate cancer.The invention also relates to compositions for inhibiting prostate cancer growth and / or progression, in particular of ERG fusion-positive prostate cancers, more in particular prostate cancers expressing a methylated ERG protein comprising a methylated lysine residue K362, in a subject comprising an amount of an antibody of the invention, optionally in combination with an amount of an antitumoral agent, wherein the amounts of the antibody and of antitumoral agent are together effective in inhibiting tumor growth and / or progression.Diagnostic Methods of UseThe antibodies according to the invention may use also as diagnostic tools for rapid detection of a methylated ERG protein in a sample, in particular also for detection of a prostate cancer,more preferably fusion-positive prostate cancer, more in particular prostate cancers expressing a methylated ERG protein comprising a methylated lysine residue K362.In another aspect, the invention provides diagnostic methods. The antibodies according to any of the embodiments of the invention can be used to detect a methylated ERG protein according to any of the variants disclosed herein in a biological sample in vitro, ex-vivo or in vivo. In one embodiment, the invention provides a method for diagnosing the presence or location of said mERG protein, and in particular of a prostate cancer expressing such mERG protein in a subject in need thereof. The antibodies of the invention can be used in a conventional immunoassay, including, without limitation, an ELISA, an RIA, flow cytometry, tissue immunohistochemistry, Western blot (immunoblot) or immunoprecipitation. The antibodies of the invention can be used to detect mERG protein from humans. The invention provides a method for detecting mERG protein according to any of the variants disclosed herein in a biological sample, comprising contacting the biological sample with an antibody of the invention and detecting the bound antibody. In one embodiment, the antibody of the invention is directly labelled with a detectable label. In another embodiment, said antibody (the first antibody) is unlabelled and a second antibody or other molecule that can bind the mERG antibody is labelled. As is well known to one of skill in the art, a second antibody is chosen that is able to specifically bind the particular species and class of the first antibody. For example, if the selected antibody is a human IgG, then the secondary antibody could be an anti-human-IgG. Other molecules that can bind to antibodies include, without limitation, Protein A and Protein G, both of which are available commercially, e.g., from Pierce Chemical Co. Example of biological samples to use in the diagnostic methods herein disclosed are urine, stool, blood, saliva, biopsies, cerebrospinal fluid, nasopharyngeal and oropharyngeal wash, sputum, endotracheal aspirate, bronchoalveolar lavage or other biological samples obtainable from a human subject.Suitable labels for the antibody or secondary antibody have been disclosed supra, and include various enzymes, prosthetic groups, fluorescent materials, luminescent materials and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, [beta]-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin / biotin and avidin / biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; anexample of a luminescent material includes luminol. In other embodiments, mERG protein can be assayed in a biological sample by a competition immunoassay utilizing mERG protein standards labelled with a detectable substance and an unlabelled antibody of the invention. In this assay, the biological sample, the labelled mERG standards and the antibody are combined and the amount of labelled mERG protein standard bound to the unlabelled antibody is determined. The amount of mERG protein in the biological sample is inversely proportional to the amount of labelled mERG protein standard bound to the antibody. One can use the immunoassays disclosed above for a number of purposes. For example, the antibodies can be used to detect mERG proteins in cultured cells or as a diagnostic assay in samples from a subject, in particular mERG proteins comprising the methylated lysine residue K632. The diagnostic methods according to any embodiments herein disclosed may be followed by a further step of the administration in the positive subject of at least an antibody of the invention, for example according to any of the Therapeutic Methods herein disclosed.Therapeutic Methods of UseIn another embodiment, the invention provides a method for treating prostate cancer, in particular fusion-positive prostate cancer, by administering an antibody or antigen binding portion thereof, and / or a nucleic acid molecule or vector, and / or a composition according to any of the embodiments disclosed herein to a patient in need thereof. Any of the types of antibodies described herein may be used therapeutically. In various embodiments, said antibody is a monoclonal antibody according to any of the variants disclosed herein. In some embodiments, the antibody, or antigen-binding portion thereof, is a minibody or single-chain antibody according to any of the variants disclosed herein.In some embodiments, the patient is a human patient. Alternatively, the patient may be a mammal affected by prostate cancer, in particular by fusion positive prostate cancer. In one embodiment, the invention provides methods of treating, aiding in the treatment, preventing or aiding in the prevention of a prostate cancer, and conditions or disorders resulting from such disease, in a subject by administering to the subject a therapeutically -effective or prophylactically effective amount of an antibody of the invention. Antibodies and antigenbinding fragments thereof which are antagonists of mERG protein can be used as therapeutics for such infection. The antibody may be administered locally or systemically.The therapeutic compositions comprising one or more antibodies according to any of the embodiments disclosed herein may be administered to the subject, for example, orally, nasally, vaginally, buccally, rectally, via the eye, or via the pulmonary route, in a variety of pharmaceutically acceptable dosing forms, which will be familiar to those skilled in the art. For example, the antibodies may be administered via the nasal route using a nasal insufflator device. The antibodies can also be administered to the eye in a gel formulation. For example, before administration, a formulation containing one or more antibodies according to any of the embodiments disclosed herein may be conveniently contained in a two-compartment unit dose container, one compartment containing a freeze-dried antibody preparation and the other compartment containing normal saline. The dosage of antibody will generally be in the range of 0.1-100 mg / kg, more preferably 0.5-50 mg / kg, more preferably 1-20 mg / kg, and even more preferably 1-10 mg / kg. The serum concentration of the antibody may be measured by any method known in the art.In another embodiment, the antibodies of the present invention are administered to the subject in combination with other therapeutic agents. In one embodiment, the additional therapeutic agents may be treating the symptoms of prostate cancer and may optionally synergize with the effects of the antibodies. The additional agent that is administered may be selected by one skilled in the art for treating the tumor. Co-administration of the antibody with an additional therapeutic agent (combination therapy) encompasses administering a composition comprising the antibody and the additional therapeutic agent as well as administering two or more separate compositions, one comprising the antibody and the other(s) comprising the additional therapeutic agent(s). Further, although co-administration or combination therapy generally means that the antibody and additional therapeutic agents are administered at the same time as one another, it also encompasses instances in which the antibody and additional therapeutic agents are administered at different times. For instance, the antibody may be administered once every three days, while the additional therapeutic agent is administered once daily. Alternatively, the antibody may be administered prior to or subsequent to treatment with the additional therapeutic agent, for example after a patient has failed therapy with the additional agent. Similarly, administration of any of the antibodies of the invention may be administered prior to or subsequent to other therapy.Said antibody and one or more additional therapeutic agents (the combination therapy) may be administered once, twice or at least the period of time until the condition is treated,palliated or cured. Preferably, the combination therapy is administered multiple times. The combination therapy may be administered from three times daily to once every six months. The administering may be on a schedule such as three times daily, twice daily, once daily, once every two days, once every three days, once weekly, once every two weeks, once every month, once every two months, once every three months and once every six months, or may be administered continuously via a minipump. The combination therapy may be administered via an oral, mucosal, buccal, intranasal, inhalable, intravenous, subcutaneous, intramuscular, or parenteral. In certain aspects, the invention provides a method for treating, preventing or alleviating the symptoms of prostate cancer, in a subject in need thereof, comprising the step of administering to said subject an antibody or antigen-binding portion according to any one of the preceding embodiments, further comprising at least one additional therapeutic agent such as an antitumoral agent.In certain aspects, the invention provides a kit for treating, preventing or alleviating the symptoms of prostate cancer, in particular fusion -positive prostate cancer in a subject in need thereof, comprising one or more antibodies or antigen binding portion thereof, and / or nucleic acid molecules and / or vectors and / or compositions according to any of the embodiments disclosed herein.The antibody or antigen-binding portion thereof herein disclosed may also be used advantageously as a diagnostic reagent in an in vitro method for detecting in a biological sample previously obtained from a patient (such as for example a serum, plasma, blood sample or any other suitable biological material, obtained from the patient, preferably a human being) anti-mERG antibodies. These antibodies may be found in the biological sample obtained from the patient for instance as a result of a previous exposure to the virus, or because a monoclonal antibody of the invention had been previously administered to the patient for therapeutic or prophylactic or research purposes. Thus, a diagnostic kit comprising the human monoclonal antibody or antigen-binding portion thereof herein disclosed of the invention, as a specific reagent, also falls within the scope of the invention, said kit being in particular designed for the detection and / or quantification, in a biological sample previously obtained from a patient, of anti-mERG protein antibodies.The antibody or antigen-binding portion thereof herein disclosed, or else any nucleic acid molecule or vector as herein disclosed may also be used advantageously for the design of avaccine against prostate cancer. Structural characterization of the Ab-antigen complex may be used to instruct antigen design. Thus, also a method or the use of the human monoclonal antibody or antigen-binding portion thereof herein disclosed for the design of a vaccine against a prostate cancer, in particular against a fusion-positive prostate cancer is within the scope of the invention.The antibody or antigen-binding portion thereof herein disclosed may be used for the preparation of mimotopes, such as for example anti-idiotype antibodies, peptides, or artificial forms or others, endowed with the ability of evoking the antibodies herein disclosed. Among these, the anti-idiotype antibodies are preferred. The anti-idiotype antibodies are antibodies specifically directed against the idiotype of the neutralizing antibodies used for the manufacture thereof, and thus are able to mimic the key epitopes that they recognize. The manufacture of anti-idiotype antibodies is carried out by per se known methodologies that do not need further detailed explanations here. Thus, also mimotopes, preferably anti-idiotype antibodies, directed against an antibody of the invention fall within the scope of the invention. The human monoclonal antibody or antigen-binding portion thereof herein disclosed may be used for the manufacture of anti-idiotype antibodies according to methods per se known. Anti-idiotype antibodies are antibodies specifically directed towards the idiotype of the broad-range neutralizing antibodies used to prepare them, and as such are able to mimic the key epitopes they recognize. Therefore, anti-idiotype antibodies directed against a monoclonal antibody of the invention are also included in the scope of the invention.***The following experimental section is provided solely by way of illustration and not limitation and does not intend to restrict the scope of the invention as defined in the appended claims. The claims are an integral part of the description.EXAMPLES1. Development of a monoclonal antibody against methylated ERGThe data obtained by the Inventors strongly support that the methylation of K362 in the ERG protein is a key step in oncogenic activation and progression toward metastatic and castration-resistant disease. Herein it is provided a monoclonal antibody selectively targeting mono-methylated ERG at K362. Detailed analysis of the interaction between ERG and DNA in crystal structures 17 and MDS13 indicated that the region of the protein involved in thecomplex formation with DNA is exposed and accessible to an antibody. Furthermore, the structural analysis showed that binding an antibody to an epitope containing K362 would prevent the complex formation with DNA, thus acting as an inhibitor (Figure 1 A). Before immunization MDS of several small peptides centered around K362 was performed to verify their stability. This analysis indicated that the sequence between 356 and 369 (WT-P15) was optimal. Therefore, the mono-methylated ERG-peptide RRWGER[MetK]SKPNMNY, METH-P15, was used to immunize mice. Next, the supernatants from multiple clones were screened tor binding to METH-P15 and non-binding to WT-P15, in standard ELISA assays. This process led lo identifying a clone (13H2-1) with the desired properties.The selected antibody (13H2-1) was expressed in large quantities using hybridoma cells. A series of tests were performed to assess its selectivity, specificity, and potency. In these experiments, the affinity of 13H2-1 to the peptide 356-RRWGERKSKPNMNY-369 (SEQ ID No 2) was determined with WT lysine 362 and mono-, di- or tri-methylated peptides (Figure IB, up per panel). The EC50 for the mono-methylated peptide is 134 ng / ml, while the EC50 for di- and tri- are 213 ng / ml and > 106ng / ml, respectively. Importantly, the EC50 for WT-P15 is 10864 ng / ml. From this, we conclude that 13H2-1 recognizes efficiently and specifically mono-methylated ERG. Next, we assessed that 13H2-1 recognizes only METH- PIS and not mono-methylated lysine in other sequence contexts. We also evaluated its binding to other methylated proteins interacting and modified by EZH2 (Figure IB, lower panel). To this end, we synthesized a ROR alpha peptide 31- LNQESAR[MetK]SEPPAPV- 45 (SEQ ID No.13), which EZH2 also methylates, and two 'scrambles' peptides, i.e., peptides with the exact composition of METH-P15 but randomly permuted sequence. We found that 13H2-1 has a detectable affinity only for METH-P15. From these data, we conclude that 13H2-1 binds selectively methylated ERG.The single-chain minibody scFv from 13H2-1 still binds mERG.Hybridoma cells were sequenced to obtain the nucleotide sequence of the heavy and light chains of the antibody. We then designed a single chain mini-body (scFv-13H2-l) consisting of the antigen binding domains of 13H 2-1, linked together with a flexible linker, and a C- terminal 6xHis-tag (Figure 1C). scFv-13H2-l was cloned into the mammalian expression vector pcDNA31 (+) (GenScnpt), expressed in Expi293F cells (ThermoFisher) and purified from cell supernatants using an IMAC column. As reformatting sometimes abolishesbinding, we performed an SPR experiment to measure the binding affinity. Measurement confirmed that scFv-13H2-l still binds METH-1 SP with a Kd of < InM.Intracellular scFv-13H2-l impacts ERG transcriptional and oncogenic activityTo investigate the effects of scFv-13H2-l on mERG in cancer cells a construct containing the scFv-13H2-l and a C-terminal HA-tag (scFv-CYT) was designed for cytoplasmic localization. An additional construct had the nuclear localization signal (scFV-NLS) from SV40 T antigen (Figure ID). Next, HEK293 cells were transfected with both plasmids to evaluate their expression and intracellular localization lacking advantage of the HA-tag for their detection. Immunofluorescence analyses showed that both constructs were expressed and localized intracellularly in the expected compartments. Specifically, scFv-CYT localized to in the cytosol and svFv-NLS the nucleus. At this point, we evaluated the effects of intracellularly expressed scFv-13H2-l on ERG transcriptional activity. To this end, we performed ETS luciferase reporter assays in ERG fusion-positive VCAP cells. We observed a significant signal reduction at 24 and 48 hours in VCAP transfected cells (scFv-CYT and scFv-NLS).These data indicate that the single-chain intra-body inhibits ERG activity, reducing its ability to activate the ETS reporter. To understand the biological consequences of ERG inhibition, we assessed the impact on the cancer stem cell compartment (CSC) using the sphere formation assay (SFA) by transfecting both plasmids in VCAP cells, a human prostate cancer cell line ERG translocation positive. Interestingly, this experiment showed significant inhibition of the CSC compartment in VCAP cells transfected with the two scFv-13H2-l constructs compared to the cells transfected with the control plasmid. As a further test of the actvity of the anti-mERG intrabodies we have used a murine cell line (EPG2) derived from a genetically engineered prostate cancer model, the Pb- Cre4Ptenflox / flox;Rosa26ERG / ERG(ERG / PTEN) mice. Prostate tumors formed in the ERG / PTEN mice have enhanced ERG methylation and activation of the ERG / EZH2 axis. Expression by the scFv-CYT and scFv-NLS intrabodies in EPG2 cells significantly reduced proliferation, tumor-sphere growth, and the ability to migrate compared to cells transfected with control plasmid. Collectively, these results demonstrate the efficacy of the anti-mERG intrabody to reverse ERG transcriptional and oncogenic activity.To test the feasibility of this approach in vivo we established EPG2 xenografts in NRG mice. When the tumor reached the size of 100mm3mice were randomized and injectedintravenously with the anti-mERG construct (p-ERG-NLS), the control plasmid (P-CTRL) and vehicle. An additional injection was performed on day 8. Mice were sacrificed after seven days (day 15 from the first injection) (Figure 2A). Plasmids were complexed with in vivo JetPrime, a formulation suitable for in vivo delivery of nucleic acids. Mouse body weight was similar between the groups, supporting the lack of toxicity of the treatment. We observed a significantly reduced tumor growth in mice treated with the anti-mERG Ab compared to the control groups (Figure 2B). Furthermore, dissociated tumor cells from the treated xenografts formed fewer tumor spheres than the control xenografts (Figure 2C). Overall, these data support the efficacy of the anti-mERG to reduce tumor growth and impair tumor-initiating stem cells, two phenotypes associated with ERG activation. The mERG protein level was also significantly reduced in EPG2 xenografts when assessed by immunohistochemistry (Figure 2D). Notably, cleaved caspase 3, a marker of apoptotic cell death, was considerably higher in treated mice xenografts than in the control groups (Figure 2E-F). These data support the efficacy of the anti-mERG Ab in antagonizing active ERG activity leading to tumor shrinkage in mice.Declaration according to Art. 170bisIn compliance with Art. 170bis of the Italian code of industrial property, the applicant of the present patent application declares that: -For the biological material, containing microorganisms or genetically modified organisms, object or used in the aforementioned patent application, the obligations deriving from national or Community regulations, and in particular, from the provisions referred to in paragraph 6 of the Legislative Decree of 12 April 2001 n.206 and 8 July 2003 n. 224, 10 concerning these modifications, have been respected. The study was approved by local ethics committees.Sequence Listing in the description>SEQ ID NO: 1 Aminoacidic sequence of the wild-type human ERG proteinMIQTVPDPAAHIKEALSWSEDQSLFECAYGTPHLAKTEMTASSSSDYGQTSKMSPRVPQ QDWLSQPPARVTIKMECNPSQVNGSRNSPDECSVAKGGKMVGSPDTVGMNYGSYMEEKHM PPPNMTTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFQNIDGKELCKMTKDDFQRLTPSYNADILLSHLHYLRETPLPHLTSDDVDKALQNSPRLMHARNTGGAAFI FPNTSVYPEATQRITTRPDLPYEPPRRSAWTGHGHPTPQSKAAQPSPSTVPKTEDQRPQLDPYQILGPTSSRLANPGSGQIQLWQFLLELLSDSSNSSCITWEGTNGEFKMTDPDEVARRWGERKSKPNMNYDKLSRALRYYYDKNIMTKVHGKRYAYKFDFHGIAQALQPHPPESSLYKYPSDLPYMGSYHAHPQKMNFVAPHPPALPVTSSSFFAAPNPYWNSPTGGIYPNTRLPTSHMPS HLGTYY>SEQ ID NO:2 epitope of mERG proteinRRWGER[MetK] SKPNMNY>SEQ ID NO: 3 epitope of mERG proteinRWGER[MetK] SKPNMN>SEQ ID NO:4 epitope of mERG proteinWGER[MetK] SKPNM>SEQ ID NO: 5 epitope of mERG proteinWGER[MetK]SKPN>SEQ ID NO: 6 epitope of mERG proteinGER[MetK] SKPNM>SEQ ID NO: 7 epitope of mERG proteinGER[MetK]SKPN>SEQ ID NO: 8 amino acid sequence of the heavy chain variable domain of the monoclonal antibody herein denoted as 13H2-1MEVHLQQSGPELVKPGASVKISCKASGYTFTDYYMNWVKQSHEKSLEWIGDINPNNGLTTYNQKFKGKATSTVDKSSSTAYMELRSLTSEDSAVYYCAREKIYYYDKNYITYWYFDVWGTGTTVTVSS>SEQ ID NO: 9 amino acid sequence of the light chain variable domain of the monoclonal antibody herein denoted as 13H2-1DIQMNQSPSSLSASLGDTITITCHASQNINVWLSWYQQKPGNAPKLLIYKTSNLHTGVPTRFSGSGSGTGFTLTISSLQPEDIATYYCQQGQSYPLTFGGGTKLEIK>SEQ ID NO: 10 nucleic acid sequence of the heavy chain variable domain of the monoclonal antibody herein denoted as 13H2-1ATGGGATGGAGCTGGATCTTTCTCTTTCTCCTGTCAGGAACTGCAGGTGTCCTCTCTGAGGTCCACCTGCAACAATCTGGACCTGAGTTGGTGAAGCCTGGGGCTTCAGTGAAGATTTCCTGTAAGGC T T C T GGATACACGT T GAG T GAG TAG TACAT GAAC T GGGT GAAACAGAGCCAT GAAAAAAG C C T T GAG T G GAT T G GAGAT AT T AAT C C T AAC AAT GGTCTTACTACT T AC AAT GAGAAATTCAAGGGCAAGGCCACATCGACTGTTGACAAGTCCTCCAGCACAGCCTACATGGAGCTCCGCAGCCTGACATCTGAGGACTCTGCTGTCTATTACTGTGCAAGAGAAAAAATTTATTACTACGATAAAAACTACATTACCTACTGGTACTTCGATGTCTGGGGCACAGGGACCACGGTCACCGTCTCCTCAGCCAAAACGACACCCCCATCTGTCTATCCACTGGCCCCTGGATCTGCTGCCCAAACTAACTCCATGGTGACCCTGGGATGCCTGGTCAAGGGCTATTTCCCTGAGCCAGTGACAGTGACCTGGAACTCTGGATCCCTGTCCAGCGGTGTGCACACCTTCCCAGCTGTCCTGCAGTCTGACCTCTACACTCTGAGCAGCTCAGTGACTGTCCCCTCCAGCACCTGGCCCAGCCAGACCGTCACCTGCAACGTTGCCCACCCGGCCAGCAGCACCAAGGTGGACAAGAAAATTGTGCCCAGGGATTGTGGTTGTAAGCCTTGCATATGTACAGTCCCAGAAGTATCATCTGTCTTCATCTTCCCCCCAAAGCCCAAGGATGTGCTCACCATTACTCTGACTCCTAAGGTCACGTGTGTTGTGGTAGACATCAGCAAGGATGATCCCGAGGTCCAGTTCAGCTGGTTTGTAGATGATGTGGAGGTGCACACAGCTCAGACGAAACCCCGGGAGGAGCAGATCAACAGCACTTTCCGTTCAGTCAGTGAACTTCCCATCATGCACCAGGACTGGCTCAATGGCAAGGAGTTCAAATGCAGGGTCAACAGTGCAGCTTTCCCTGCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGCAGACCGAAGGCTCCACAGGTGTACACCATTCCACCTCCCAAGGAGCAGATGGCCAAGGATAAAGTCAGTCTGACCTGCATGATAACAAACTTCTTCCCTGAAGACATTACTGTGGAGTGGCAGTGGAATGGGCAGCCAGCGGAGAACTACAAGAACACTCAGCCCATCATGGACACAGATGGCTCTTACTTCGTCTACAGCAAGCTCAATGTGCAGAAGAGCAACTGGGAGGCAGGAAATACTTTCACCTGCTCTGTGTTACATGAGGGCCTGCACAACCACCATACTGAGAAGAGCCTCTCCCACTCTCC TGGTAAATGA>SEQ ID NO: 11 nucleic acid sequence of the light chain variable domain of the monoclonal antibody herein denoted as 13H2-1ATGAGGGTCCTTGCTGAGCTCCTGGGGCTGCTGCTGTTCTGCTTTTTAGGTGTGAGATGTGACATCCAGATGAACCAGTCTCCATCCAGTCTGTCTGCATCCCTTGGAGACACAATTACCATCACTTGCCATGCCAGTCAGAACATTAATGTTTGGTTAAGCTGGTACCAGCAGAAACCAGGAAATGCTCCTAAACTATTGATCTATAAGACTTCCAATTTGCACACAGGCGTCCCAACAAGGTTTAGTGGCAGCGGATCTGGAACAGGTTTCACATTGACCATCAGCAGCCTGCAGCCTGAAGACATTGCCACTTACTACTGTCAACAGGGCCAAAGTTATCCTCTGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAACGGGCTGATGCTGCACCAACTGTATCCATCTTCCCACCATCCAGTGAGCAGTTAACATCTGGAGGTGCCTCAGTCGTGTGCTTCTTGAACAACTTCTACCCCAAAGACATCAATGTCAAGTGGAAGATTGATGGCAGTGAACGACAAAATGGCGTCCTGAACAGTTGGACTGATCAGGACAGCAAAGACAGCACCTACAGCATGAGCAGCACCCTCACGTTGACCAAGGACGAGTATGAACGACATAACAGCTATACCTGTGAGGCCACTCACAAGAC AT C AAC T T C AC C CAT T GT C AAGAG C T T C AAC AG GAAT GAGT GT T AG>SEQ ID NO: 12 nucleic acid sequence of the minibody herein denoted as scFv-13H2-latggaagtgcacctgcagcaatctggacctgagctggtgaaacctggcgcctctgtgaagatcagctgcaaggccagcggctacacctttaccgactactaca tgaactgggtcaagcagagccacgagaagtccctggaatggatcggagatatcaaccccaacaacggcctgacaacatacaaccagaagttcaagggcaa ggctacatctaccgtggacaagagcagcagcaccgcctacatggaactgcggagcctgaccagcgaggacagcgccgtgtactattgtgccagagagaaa atctactactatgataagaattacatcacctactggtacttcgacgtgtggggcacaggcaccacagtgaccgtgtccagcggcggcggaggcagcggcggc ggcggatctggcggcggaggcagcgatatccagatgaaccagagcccatctagcctctccgccagcctgggcgacaccattacaatcacctgtcacgcctc ccagaacatcaacgtgtggctgagctggtaccagcagaaacccggcaatgcccctaagctgctgatctacaagaccagcaacctgcacaccggcgtgccca ccagattcagcggatctggcagcggcaccggctttaccctgaccatcagcagcctgcagcctgaggacatcgctacatactactgccagcaaggccagtctt atcctctgacattcggcggcggaacaaagctggaaatcaaggcggccgcctacccatacgacgtcccagactacgctggaggtggaactcctccaaagaag aaacgtaaggtttaa >SEQ ID NO: 13 amino acid sequence of the exemplified ROR alpha peptideLNQES AR[MetK] SEPP AP V

Claims

CLAIMS1. An antibody or an antigen-binding portion thereof capable of specifically binding to a methylated ERG protein.

2. The antibody or an antigen-binding portion thereof according to claim 1, wherein said antibody or antigen-binding portion thereof is capable of specifically binding to an epitope of said methylated ERG protein comprising a methylated lysine residue.

3. The antibody or an antigen-binding portion thereof according to claim 2, wherein said methylated lysine residue corresponds to residue K362 of said ERG protein, in particular wherein the lysine residue K362 is determined with reference to the aminoacidic sequence of the wild-type human ERG protein set forth in SEQ ID No 1.

4. The antibody or an antigen-binding portion thereof according to claims 2 or 3, wherein said methylated lysine residue is a mono-methylated lysine residue.

5. The antibody or an antigen-binding portion thereof according to any one of claims 2 to 4, wherein said epitope is a peptide comprising or consisting of an aminoacidic sequence selected from the group consisting of:RRWGER[MetK]SKPNMNY (SEQ ID No. 2):RWGER[MetK]SKPNMN (SEQ ID No. 3);WGER[MetK]SKPNM (SEQ ID No. 4);WGER[MetK]SKPN (SEQ ID No. 5):GER[MetK]SKPNM (SEQ ID No. 6); and GER[MetK]SKPN (SEQ ID No. 7).

6. The antibody or an antigen-binding portion thereof according to any one of claims 1 to 5, which is selected from a monoclonal antibody, a minibody, a multi-specific antibody, a bi-specific antibody, a three-specific antibody, a scFV, a diabody, a triabody, a tetrabody, a linear antibody, a chelating recombinant antibody, a tribody, a bibody, an intrabody, a nanobody, an antibody-drug conjugate, a binding-domain immunoglobulin fusion protein, a fusion antibody, animmunoadhesin, or an antigen binding fragment thereof, preferably is selected from a monoclonal antibody and a minibody.

7. The antibody or an antigen-binding portion thereof according to any one of claims 1 to 6, wherein said antibody is a monoclonal antibody or an antigen-binding portion thereof comprising a heavy chain variable domain (VH) having the amino acid sequence set forth in SEQ ID No. 8 and a light chain variable domain (VL) amino acid sequence set forth in SEQ ID No:9.

8. The antibody or an antigen-binding portion thereof according to any one of claims 1 to 7, wherein said antibody or an antigen-binding portion thereof is a minibody encoded by a sequence set forth in SEQ ID No. 12.

9. The antibody or an antigen-binding portion thereof according to any one of claims 1 to 8, which specifically binds to said methylated ERG protein with an affinity constant (KD) of equal to or less than about 1 nM as measured by surface plasmon resonance (SPR).

10. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes an antibody or an antigen-binding portion thereof as defined in any one of claims 1 to 9, preferably wherein said isolated nucleic acid molecule comprises or consists of a sequence selected from SEQ ID No. 10 and SEQ ID No. 11 or wherein said isolated nucleic acid molecule comprises or consists of SEQ ID No. 12, preferably said nucleic acid molecule is a DNA or mRNA molecule.

11. A vector or a nanoparticle comprising a nucleic acid molecule as defined in claim 10, wherein the vector optionally comprises an expression control sequence operably linked to said nucleic acid molecule.

12. A pharmaceutical composition comprising one or more antibody, or an antigen-binding portion thereof as defined in any one of the claims from 1 to 9, and / or one or more nucleic acid molecules as defined in claim 10, and / or one or more vectors or nanoparticle as defined in claim 11, and a pharmaceutically acceptable carrier.

13. The antibody or an antigen-binding portion thereof according to any one of claims 1 to 9, the nucleic acid molecule according to claim 10, the vector or nanoparticle according to claim 11 or the pharmaceutical composition according to claim 12, for use in a prophylactic and / or therapeutic treatment of a prostate cancer in a subject in need thereof, preferably wherein said cancer is a ERG fusion-positive prostate cancer.

14. An in vitro method for the diagnosis and / or prognosis and / or to monitor the development of a prostate cancer in a subject comprising the following step: i) determining and / or quantifying the expression levels of a methylated ERG protein in a sample isolated from said subject; preferably wherein said prostate cancer is a ERG fusion-positive prostate cancer.

15. Use of an antibody or an antigen-binding portion thereof according to any one of the claims from 1 to 9, or of a nucleic acid according to claim 10 for the design of a vaccine against prostate cancer.

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