USE OF ACYL CYANAMIDES OR THEIR SALTS FOR REGULATING PLANT GROWTH

Abstract

The present invention relates to the use of acyl cyanamides or salts thereof as an active ingredient of plant growth regulators, in particular for breaking dormancy in fruit trees.

Description

NEW PEPTIDES AND NEW COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST PANCREAS AND OTHER TYPES OF CANCER n / ccnn / zznz / E / YiAi The present invention relates to peptides, proteins, nucleic acids and cells intended for use in immunotherapeutic methods. In particular, the present invention relates to cancer immunotherapy. The present invention also relates to peptide epitopes for tumor-associated T lymphocytes, alone or in combination with other tumor-associated peptides, which, for example, can serve as active pharmaceutical ingredients in vaccine compositions intended to stimulate antitumor immune responses, or to stimulate ex vivo T lymphocytes that will later be transferred to patients. Peptides bound to major histocompatibility complex (MHC) molecules, or peptides as such, can also be targets of antibodies, soluble T cell receptors, and other binding molecules. The present invention relates to several novel peptide sequences and their variants derived from HLA class I molecules of human tumor cells that can be used in vaccine compositions to trigger antitumor immune responses or as targets for the development of compounds and cells pharmaceutically or immunologically. assets. Background of the invention Pancreatic cancer is one of the most aggressive and deadly types of cancer that exist. In 2012 it was the 12th most common type of cancer in men, with 178,000 cases, and the 11th most common in women, with 160,000 cases in the world. That same year, 330,000 deaths were recorded, making pancreatic cancer the seventh cause of cancer death (World Cancer Report, 2014). Pancreatic cancer is not a single tumor entity, but several different types can be distinguished. Exocrine tumors account for around 95% of all pancreatic cancer cases and include ductal and acinous adenocarcinomas, mucinous papillary intraductal neoplasms (IPMN), solid pseudopapillary neoplasms, mucinous cystic adenomas, and serous cystadenomas. . The remaining 5% of pancreatic cancer cases belong to the subgroup of pancreatic neuroendocrine tumors (World Cancer Report, 2014). Infiltrating duct adenocarcinoma constitutes the most aggressive form of pancreatic cancer and due to its high frequency (90% of all pancreatic cancers), epidemiological data usually refer mainly to this specific type (World Cancer Report, 2014). In 2012, 68% of new cases appeared in developed countries, with the highest incidence in central and eastern Europe, North America, Argentina, Uruguay and Australia. In contrast, most countries in Africa and East Asia have low incidences. On a global scale, incidence rates appear to be quite stable over time in both sexes (World Cancer Report, 2014). The absence of specific symptoms means that pancreatic cancer is usually diagnosed at an advanced stage, often metastatic. The prognosis after diagnosis is frankly negative, with a 5-year survival rate of only 5% and a mortality / incidence ratio of 0.90 (World Cancer Report, 2014). Several factors appear to increase the risk of pancreatic cancer, including age, since most patients are older than 65 at the time of diagnosis, and race, since the African-American population in the United States has a risk 1.5 times greater than the white population. Other risk factors are smoking, obesity, diabetes, having an ABO blood group other than O, pancreatitis and a family history of pancreatic cancer (World Cancer Report, 2014). Up to 10% of all pancreatic cancer cases are believed to have a familial basis. Germline mutations in the following genes have been associated with an increased risk of developing pancreatic cancer: p16 / CDKN2A, BRCA2, PALB2, PRSS1, STK11, ATM, and error repair genes. DNA pairing. Furthermore, sporadic cases of pancreatic cancer are also characterized by the presence of mutations in various oncogenes and oncosuppressor genes. The most frequent mutations in ductal adenocarcinoma affect the oncogenes KRAS (95%) and AIB1 (up to 60%) and the oncosuppressor genes TP53 (75%), p16 / CDKN2A (95%) and SMAD4 (55%) ( World Cancer Report, 2014). The therapeutic options available for patients with pancreatic cancer are extremely limited. One of the main problems in achieving effective treatment is how advanced the tumor usually is when it is diagnosed. Furthermore, pancreatic cancer is quite resistant to chemotherapeutics, which could be caused by the dense, hypovascularized desmoplastic stroma of the tumor. According to guidelines published by the German Cancer Society, the German Cancer Aid Association and the Association of German Scientific Medical Societies, the only curative treatment option available is tumor resection. Resection is recommended if the tumor is limited to the pancreas or if metastases are limited to adjacent organs. Resection is not recommended if the tumor already has distant metastases. Resection is followed by adjuvant chemotherapy with gemcitabine or 5-fluorouracil + / - leucovorin for six months (S3-Leitlinie Exokrines Pankreaskarzinom, 2013). Patients with inoperable advanced-stage tumors can be treated with a combination of chemotherapy and chemoradiotherapy (S3-Leitlin¡e Exokrines Pankreaskarzinom, 2013). The standard of care for palliative chemotherapy is gemcitabine, either as monotherapy or in combination with erbolitinib, an epidermal growth factor (EGF) receptor tyrosine kinase inhibitor. Other alternatives consist of the combination of 5fluorouracil, leucovorin, irinotecan and oxaliplatin, also called FOLFIRINOX protocol, or the combination of gemcitabine with nabpaclitaxel, which has shown greater effects than monotherapy with n / ccnn / zznz / Ε / γΐΛΐ gemcitabine in the study MPACT(Von Hoff et al., 2013; S3-Leitlin¡e Exokrines Pankreaskarzinom, 2013). The high mortality / incidence ratio highlights the urgent need for new, more effective therapeutic strategies against pancreatic cancer. Targeted therapies, which have already proven effective in other types of cancer, represent an interesting option. Given the situation, various studies have been carried out with the purpose of evaluating the benefit provided by targeted therapies in advanced pancreatic cancer, unfortunately with very little success (Walker and Ko, 2014). However, the genetic diversity of pancreatic cancer opens the door to the possibility of personalized treatments, as is the case of invasive ductal adenocarcinoma, which has been shown to be more sensitive to the inactivation of the two alleles of the BRCA2 and PALB2 genes that to treatment with poly(ADP-ribose) polymerase inhibitors and mitomycin C (World Cancer Report, 2014). Acting against the tumor stroma constitutes an alternative strategy to develop new treatments against pancreatic cancer. The dense, hypovascular stroma that characterizes it could well act as a barrier against chemotherapeutics and has been shown to emit signals that promote tumor proliferation and invasion as well as the maintenance of cancer stem cells. For this reason, different preclinical and clinical studies have been designed to analyze the effect of stroma elimination and inactivation (Rucki and Zheng, 2014). As another innovative and encouraging alternative, therapeutic vaccines against pancreatic cancer are also currently being investigated. Peptide vaccines targeting mutations of KRAS, reactive telomerase, gastrin, survivin, CEA and MUC1 have already been evaluated in clinical trials, partly with promising results. Likewise, clinical trials carried out with dendritic cell vaccines, allogeneic GM-CSF secreting vaccines and algenpantucel-L in cancer patients have also revealed beneficial effects of immunotherapy. In addition, other clinical studies are ongoing investigating the effectiveness of various n / ccnn / zznz / Ε / γΐΛΐ vaccination protocols (Salman et al., 2013). In light of the serious side effects and high cost of cancer treatment, there is a need to discover new factors that can be used in oncological treatment in general and pancreatic cancer in particular. There is also a need to discover factors that can serve as biomarkers for cancer in general and pancreatic cancer in particular, with a view to improving diagnosis, assessment of prognosis and prediction of therapeutic success. Antitumor immunotherapy represents a treatment option directed against cancer cells that reduces side effects. Antitumor immunotherapy takes advantage of the existence of tumor-associated antigens. The current classification of tumor-associated antigens (TAA) comprises the following main groups: a) Cancer-testis antigens: The first TAAs identified that can be recognized by T lymphocytes belong to this class, which was initially called cancer-testis (CT) antigens because its members are expressed in histologically different human tumors and in normal tissues only. They are found in the spermatocytes / spermatogonia of the testis and occasionally in the placenta. As testicular cells do not express HLA class I and II molecules, these antigens cannot be recognized by T lymphocytes in normal tissues and, therefore, are considered tumor-specific from an immunological point of view. Known examples of CT antigens are members of the MAGE family and NY-ESO-1. b) Differentiation antigens: These TAA are shared by tumors and by the normal tissue from which the tumor derives. Most of the known differentiation antigens are found in melanomas and normal melanocytes. Many of these proteins related to the melanocytic lineage participate in the biosynthesis of melanin and are not tumor-specific, which does not prevent them from being widely used in cancer immunotherapy. Examples include tyrosinase and Melan-A / MART-1 in melanoma and PSA in prostate cancer. c) Overexpressed TAAs: Genes encoding widely expressed TAAs have been detected in histologically distinct tumors and in numerous normal tissues, generally with lower expression levels. It is possible that many of the epitopes processed and possibly presented by normal tissues are below the limit necessary to be recognized by T lymphocytes, but that overexpression by tumor cells breaks the tolerance in force until that moment and triggers the antitumor response. Prominent examples of this class of TAAs are Her-2 / neu, survivin, telomerase or WT1. d) Tumor-specific antigens: These unique TAAs are the result of mutations of normal genes (such as β-catenin, CDK4, etc.). Some of these molecular changes are related to neoplastic transformation and / or its progression. Tumor-specific antigens are generally capable of inducing potent immune responses without the risk of autoimmune reactions against normal tissues. On the other hand, these TAAs are almost always only relevant to the exact same tumor in which they were identified and are usually not found in many other tumors of their type. The tumor specificity (or association) of a peptide can also arise if the peptide originates from an exon of the tumor (associated with) in the case of proteins with tumor-specific (associated with) isoforms. e) TAAs resulting from abnormal post-translational modifications: These TAAs can arise from proteins that are neither specific nor overexpressed in tumors, despite which they are shown to be associated with tumors by post-translational processes that are mainly activated in tumors. Examples of this type arise from altered glycosylation patterns that generate new epitopes in tumors, as occurs with MUC1, or from phenomena such as protein splicing during degradation, which may or may not be tumor-specific. f) Oncovirus proteins: These TAAs are viral proteins that could play a critical role in the oncogenic process and that, as foreign due to their non-human origin, can trigger a lymphocyte response. T. Examples of such proteins are the E6 and E7 proteins of human papillomavirus type 16, which are expressed in cervical carcinoma. Immunotherapy based on T lymphocytes targets peptide epitopes from specific proteins of the tumor or associated with it, which are presented by molecules of the major histocompatibility complex (MHC). The antigens that are recognized by tumor-specific T lymphocytes, that is, the epitopes, can be molecules derived from all types of proteins, such as enzymes, receptors, transcription factors, etc., that are expressed and that, in comparison with unaltered cells of the same origin, are upregulated in the corresponding tumor cells. There are two types of MHC molecules: MHC class I and MHC class II. MHC class I molecules are composed of an alpha heavy chain and a beta-2-microglobulin, and class II molecules are composed of an alpha and a beta chain. Its three-dimensional conformation results in a binding cleft that mediates non-covalent interaction with peptides. MHC class I molecules are found in most nucleated cells. They present peptides from the proteolysis of mostly endogenous proteins, defective ribosomal products (DRIPs) and large peptides. However, peptides derived from endosomal compartments or exogenous sources are also frequently found bound to MHC class I molecules. This non-classical route of presentation by class I is called cross-presentation in the literature (Brossart and Bevan, 1997; Rock et al., 1990). MHC class II molecules, which are mainly found in specialized antigen-presenting cells (APCs), mainly present peptides from exogenous or transmembrane proteins that are taken up by APCs through endocytosis and then processed by them. Complexes made up of peptides and MHC class I molecules are recognized by CD8-positive T lymphocytes carrying the appropriate T cell receptor (TCR), while complexes formed by peptides and MHC class II molecules are recognized by T lymphocytes. CD4-positive cooperators carrying the appropriate TCR. It is well known that TCR, peptide and MHC are present in a stoichiometric ratio of 1:1:1. CD4-positive helper T cells play an important role in inducing and maintaining effective responses by CD8-positive cytotoxic T cells. The identification of epitopes derived from tumor-associated antigens (TAA) that are recognized by CD4-positive T lymphocytes is of utmost importance for the development of pharmaceutical products that stimulate antitumor immune responses (Gnjatic et al., 2003). Helper T lymphocytes generate within the tumor a cytokine environment that is conducive to cytotoxic T lymphocytes (CTL) (Mortara et al., 2006) and that attracts effector cells, such as the CTL themselves, NK cells , macrophages or granulocytes (Hwang et al., 2007). In the absence of inflammation, the expression of MHC class II molecules is primarily confined to cells of the immune system, specifically specialized antigen-presenting cells (APCs), such as monocytes, monocyte-derived cells, macrophages, and dendritic. In cancer patients, tumor cells have been found to express MHC class II molecules (Dengjel et al., 2006). The elongated peptides of the invention can act as active epitopes for MHC class II. T helper cells, activated by MHC class II epitopes, play an important role in coordinating the effector function of CTLs in antitumor immunity. Epitopes recognized by T helper cells that trigger a TH1 type T helper cell response support the effector functions of CD8-positive cytotoxic T cells, which include cytotoxic functions directed against tumor cells displaying MHC complexes on their surface. / tumor-associated peptide. In this way, the epitopes of tumor-associated peptides that are recognized by helper T cells, alone or in combination with other tumor-associated peptides, can serve as active pharmaceutical ingredients in compositions of tumors. vaccines intended to stimulate antitumor immune responses. In mammalian models such as mice, it has been shown that CD4-positive T lymphocytes can inhibit the manifestation of tumors even without the participation of CD8-positive T lymphocytes through the inhibition of angiogenesis through the secretion of gamma interferon ( IFN-Y (Beatty and Paterson, 2001 ; Mumberg et al., 1999). There are indications that CD4 T lymphocytes act directly as antitumor agents (Braumuller et al., 2013; Tran et al., 2014). Since constitutive expression of HLA class II molecules is typically exclusive to immune cells, the possibility of isolating class II peptides directly from primary tumors was not considered feasible. But Dengjel and co-workers discovered several MHC class II epitopes directly in tumors (WO 2007 / 028574, EP 1 760 088 B1). Given that both types of response, CD8-dependent and CD4-dependent, contribute jointly and synergistically to the antitumor effect, the identification and characterization of tumor-associated antigens recognized by CD8+ cytotoxic T lymphocytes (ligand: MHC class I molecules + peptide epitope) or by CD4+ T helper lymphocytes (ligand: MHC class II molecules + peptide epitope) is important for the development of antitumor vaccines. To trigger the cellular immune response, the MHC class I peptide must bind to an MHC molecule. This process depends on the allele of the MHC molecule and specific polymorphisms in the amino acid sequence of the peptide. Peptides that bind MHC class I are typically 8 to 12 amino acid residues in length and typically contain two conserved (“anchor”) residues in their sequence that interact with the corresponding binding cleft of the MHC molecule. Thus each MHC allele has a “binding motif” that determines which peptides can bind specifically to the binding cleft. In the MHC class I-dependent immune reaction, peptides not only have to be able to bind to certain molecules n / ccnn / zznz / E / YiAi MHC class I expressed by tumor cells also have to be recognized by T lymphocytes carrying specific TCR receptors. For proteins to be recognized by T lymphocytes as specific or tumor-associated antigens and to be used as treatment, they must meet certain prerequisites. The antigen must be expressed mainly by tumor cells and not by normal healthy tissues or, if so, it must be expressed in comparatively small amounts. In a preferred embodiment, the peptide must be presented in excess by tumor cells relative to normal healthy tissues. And it is not only convenient that the antigen of interest be present only in one type of tumor, but that it is also present in high concentrations (i.e., number of copies of the peptide per cell). Tumor-specific and tumor-associated antigens often come from proteins that are directly involved in the transformation of a normal cell into a tumor cell because of their function, for example because they are involved in the control of the cell cycle or in the suppression of apoptosis. . Furthermore, also the downstream targets of the proteins that are directly responsible for the transformation may be positively regulated and, therefore, indirectly associated with the tumor. Such antigens indirectly associated with tumors may also be targets for a vaccination strategy (Singh-Jasuja et al., 2004). In both cases it is essential that the amino acid sequence of the antigen contains epitopes, since the peptide ("immunogenic peptide") derived from a tumor-associated antigen must trigger a T lymphocyte response under in vitro or in vivo conditions. Basically, any peptide capable of binding to an MHC molecule can act as a T cell epitope. A prerequisite for the induction of a T cell response in vitro or in vivo is the presence of a T cell endowed with the corresponding TCR and the absence of immune tolerance towards that particular epitope. Therefore, TAAs are a starting point for the development of T cell-based therapy including, but not limited to, antitumor vaccines. Methods to identify and characterize n / ccnn / zznz / E / YiAi TAAs are based on the use of T lymphocytes that can be isolated from patients or healthy individuals, or are based on the generation of differential transcription profiles or expression patterns. Peptide differentials between tumors and normal tissues. However, the identification of genes overexpressed or selectively expressed in tumor tissues or in human tumor cell lines does not provide precise information about the use of the antigens transcribed from these genes in immunotherapy. This is explained because only an individual subpopulation of epitopes of these antigens is suitable for applications of this type, since there must be a T lymphocyte with the corresponding TCR and the immunotolerance towards that specific epitope must be minimal or non-existent. Therefore, in a very preferred embodiment of the invention it is important to select only those peptides that are presented in excess or selectively against which a functional and / or proliferative T lymphocyte is found. A functional T cell is defined as a T cell that, after stimulation with a specific antigen, can undergo clonal expansion and be capable of executing effector functions (“effector T cell”). In the case of directing the action against peptide-MHC complexes through specific TCRs (for example, soluble TCRs) and antibodies or other binding molecules (carriers) according to the invention, the immunogenicity of the underlying peptides is secondary. . In such cases, presentation is the determining factor. Brief description of the invention In a first aspect of the present invention, it relates to a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 67 or to a variant sequence thereof that is at least 77%, preferably at least 88% homologous (preferably at least 77% or at least 88% identical) to SEQ ID NO. 1 to SEQ ID NO. 67, wherein said variant binds to MHC and / or stimulates T lymphocytes that exhibit cross-reactivity with said peptide, or with a pharmaceutically acceptable salt thereof, wherein said peptide is not the underlying entire polypeptide. n / ccnn / zznz / E / YiAi The present invention further relates to a peptide of the present invention comprising a sequence selected from the group consisting of SEQ ID NO. 1 to SEO ID NO. 67 or a variant thereof, which is at least 77%, preferably at least 88% homologous (preferably at least 77% or at least 88% identical) to SEQ ID NO. 1 to SEQ ID NO. 67, wherein said peptide or a variant thereof has a total length of between 8 and 100, preferably between 8 and 30, and more preferably between 8 and 14 amino acids. The following tables below show the peptides according to the present invention, their respective SEQ ID NO., and the probable originating (underlying) genes of such peptides. All of the peptides in Table 1 and Table 2 bind to HLA-A*02 alleles, and the peptides in Table 2 have been previously reported in large lists resulting from ultrarapid genetic screening with high error rates or They are the result of calculation with algorithms, but until now they had not been linked to cancer at all. The peptides in Table 3 are additional peptides that could be useful if combined with the other peptides of the invention. The peptides of Tables 4 and 4.2 are also useful for the diagnosis and / or treatment of other malignant neoplasms that overexpress and / or present in excess the corresponding underlying polypeptide. n / ccnn / zznz / E / YiAi Table 1: Peptides according to the present invention SEQ ID NO. • Gene Sequence ID(s) Official Symbol(s) of Gene 1 • FLAQQESEI 1211,1212 CLTA, CLTB 2 • SLQEEHVAVA 5339 PLEC 3 • ALLTFMEQV 165 AEBP1 4 • SVDVSPPKV 113146 AHNAK2 5 • LLVDDSFLHTV 253982 ASPHD 1 6 • VLISLKQAPLV 1211 CLTA 7 • AQQESEIAGI 1211,1212 CLTA, CLTB 8 • IVDDLTINL 1303 COL12A1 9 • FLFDGSANLV 1293 COL6A3 SEQ ID NO. • Gene Sequence ID(s) Official Gene Symbol(s) 10 • FLVDGSSAL 1293 COL6A3 11 • FLYKIIDEL 1293 COL6A3 12 • FVSEIVDTV 1293 COL6A3 13 • LLAGQTYHV 1293 COL6A3 14 • VLAKPGVISV 1293 COL6A3 15 • S LANNVTSV 131566 DCBLD2 16 • APVNVTTEVKSV 158078, 1915 EEF1A1P5, EEF1A1 17 • FLKSGDAAIV 158078, 1915 EEF1A1P5, EEF1A1 18 • SLLDDELMSL 26088 GGA1 19 • HLAPETDEDDL 8100 IFT88 20 • RLAGDGVGAV 3855 KRT7 21 • HLMDQPLSV 3918 LAMC2 22 • TLDGAAVNQV 3918 LAMC2 23 • SLSAFTLFL 4060 LUM 24 • GLLEELVTV 642475 MROH6 25 • SLKEEVGEEAI 4627 MYH9 26 • SLKEEVGEEAIV 4627 MYH9 27 • YLQGQRLDNV 6447 SCG5 28 • YLQGQRLDNVV 6447 SCG5 29 • FLQEYLDAI 6317, 6318 SERPINB3, SERPINB4 30 • VVDEGPTG V 9123 SLC16A3 31 • SLAAAAGKQEL 6750 SST 32 • SLAAAAGKQELA 6750 SST 33 • SLDSRLELA 81628 TSC22D4 3. 4 . MLMPVHFLL 114131 UCN3 35 • VMDSGDGVTHTV 100996820, 344227, 345651, 440915, 445582, 60, 641455, ACTBL2, POTEKP, POTEE, ACTB, POTEM, n / ccnn / zznz / Ε / γΐΛΐ SEQ ID NO. • Gene Sequence ID(s) Official Gene Symbol(s) 653269, 653781, 71, 728378 POTEI, POTEJ, ACTG1, POTEF 36 • KQEYDESGPSIVH 100996820, 344227, 440915, 445582, 60, 64145 5, 653269, 653781 ,71.728378 POTEKP, POTEE, ACTB, POTEM, POTEI, POTEJ, ACTG1, POTEF 37 • GLLKKINSV 55107 ANO1 38 • NLVEKTPALV 10632, 267020 ATP5L, ATP5L2 39 • TLLSNLEEA 1191 CLU 40 • FILDSAETTTL 12 93 COL6A3 41 . FLLDGSEGV 1293 COL6A3 42 • KLVDKSTEL 1293 COL6A3 43 • RLDQRVPQI 1293 COL6A3 44 • VLLDKIKNLQV 1293 COL6A3 45 • VADKIHSV 11072 DUSP14 46 • TFAPVNVTTEVKSV 158078, 1915 EE F1A1P5, EEF1A1 47 • KMDASLGNLFA 10447, 51384 FAM3C, WNT16 48 • ALTQTGGPHV 2316 FLNA 49 • NLKGTFATL 100187828 , 3043, 3045 HBB, HBD 50 • ALAAILTRL 80201 HKDC1 51 . ALMLQGVDL 3329 HSPD1 52 • RMVEEIGVEL 10525 HYOU1 53 • SSFGGLGGGSV 3880 KRT19 54 • VLLSEIEVA 4134 MAP4 55 • YLDAMMNEA 103910, 10627 MYL12B, MYL12A 56 • GLLDYATGAIGSV 117 583 PARD3B 57 • FLGKVVIDV 100271927, 10156 RASA4B, RASA4 58 • GLAAFKAFL 5999 RGS4 59 • KLFNLSKEDDV 6194 RPS6 n / ccnn / zznz / Ε / γΐΛΐ SEQ ID NO. • Gene Sequence ID(s) Official Gene Symbol(s) 60 • YLEEDVYQL 23255 SOGA2 61 • ALEKDYEEVGV 10376, 113457, 7278, 7846 TUBA1B, TUBA3D, TUBA3C, TUBA1A 62 • ALEKDYEEV 10376, 1 13457, 51807, 7277 , 7278, 7846, 84790 TUBA1B, TUBA3D, TUBA8, TUBA4A, TUBA3C, TUBA1A, TUBA1C 63 • FAGDDAPR 100996820, 344227, 445582, 58, 59, 60, 653269, 65378 1, 70, 71,72,728378 POTEE, ACTA1, ACTA2 , ACTB, POTEI, POTEJ, ACTC1, ACTG1, ACTG2, POTEF 64 • FLVSNMLLAEA 113791 PIK3IP1 n / ccnn / zznz / E / YiAi Table 2: Additional peptides according to the present invention with no known prior link to cancer SEQ ID NO. Sequence Gene ID(s) Official Gene Symbol(s) 65 YLYDSETKNA 4316 MMP7 66 ALLSGLREA 23028 KDM1A 67 KMFFLIDKV 4599 MX1 Table 3: Useful peptides, among other uses, for personalized cancer therapies SEQ ID NO. Sequence Gene ID(s) Official Gene Symbol(s) 68 KLLTEVHAA 101 ADAM8 69 VMAPFTMTI 338 APOB SEQ ID NO. Sequence Gene ID(s) Official Gene Symbol(s) 70 FLVDGSWSV 1 303 COL12A1 71 FLLDGSANV 1 293 COL6A3 72 YVYQNNIYL 2191 FAP 73 TLVAIVVGV 60681 FKBP10 74 KIQEILTQV 1 0643 IGF2BP3 7 5 RLDDLKMTV 3918 LAMC2 76 RLLDSVSRL 3918 LAMC2 77 GLTDNIHLV 25878 MXRA5 78 TLSSIKVEV 25878 MXRA5 79 VLAPRVLRA 5954 RCN1 80 TLYPHTSQV 1462 VCAN 81 AMSSKFFLV 7474 WNT5A 82 SISDVIAQV 56172 ANKH 83 FLIDSSEGV 1293 COL6A3 84 NLLDLDYEL 1293 COL6A3 85 TVAEVIQSV 55083 KIF26B 86 SLLAQNTSWLL 7070 THY1 87 LLLGSPAAA 23544 SEZ6L n / ccnn / zznz / E / YiAi The present invention further relates generally to peptides according to the present invention for use in the treatment of proliferative diseases, such as, for example, lung cancer, kidney cancer, brain cancer, colon or rectal cancer, esophageal cancer, breast cancer, ovarian cancer, gastric cancer, liver cancer, prostate cancer, melanoma and leukemias. Particularly preferred are peptides - alone or in combination - according to the present invention selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 67. Even more preferable are the peptides - alone or in combinations - selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 34 (see Table 1), and its uses in immunotherapy against pancreatic cancer, lung cancer, kidney cancer, brain cancer, colon or rectal cancer, esophageal cancer, breast cancer, ovarian cancer, cancer gastric, liver cancer, prostate cancer, melanoma and leukemias, and preferably pancreatic cancer. However, as Tables 4 and 4-2 show below, many of the peptides according to the present invention are also found in other tumor types and, therefore, can also be used in immunotherapy for other indications. . See also Figure 1 and Example 1. n / ccnn / zznz / E / YiAi Table 4: Peptides according to the present invention and specific uses thereof in other proliferative diseases, especially in other types of cancer. The table contains a list of the selected peptides that have been found in other types of tumor, present in at least 5% of the tumor samples analyzed, or presented in more than 5% of the tumor samples analyzed with a ratio of the geometric means corresponding to tumor tissues with respect to those of normal tissues greater than 3. Overpresentation is defined as a higher presentation in the tumor sample than in the normal sample with greater presentation. SEQ ID NO. Sequence Other relevant organs / cancer types 3 ALLTFMEQV Lung, kidney, brain, colon, rectum and esophagus 4 SVDVSPPKV Lung, kidney and melanoma 5 LLVDDSFLHTV Kidney, brain, liver, melanoma and ovary 8 IVDDLTINL Esophagus 9 FLFDGSANLV Lung, colon, rectum, breast and esophagus 1 0 FLVDGSSAL Lung, stomach and breast 1 1 FLYKIIDEL Lung, colon, rectum and breast 12 FVSEIVDTV Lung, breast and esophagus 14 VLAKPGVISV Lung 1 5 SLANNVTSV Lung, kidney, brain, stomach, melanoma, ovary and esophagus 1 6 APVNVTTEVKSV Leukocytes 21 HLMDQPLSV Lung 23 SLSAFTLFL Lung and prostate 24 GLLEELVTV Lung, stomach and ovary 30 VVDEGPTGV Lung, kidney, brain, stomach, liver, leukocytes, breast and ovary 34 MLMPVHFLL Stomach 36 KQEYDESGPSIVH Lung and brain 39 TLLSNLEEA Brain and prostate 40 FILDSAETTTL Lung 41 FLLDGSEGV Lung, breast, ovary and esophagus 42 KLVDKSTEL Lung, colon, rectum and esophagus 43 RLDQRVPQI Lung, colon, rectum, breast and esophagus 44 VLLDKIKNLQV Lung, stomach, colon, rectum, liver, breast and melanoma 45 VADKIHSV Kidney and stomach 47 KMDASLGNLFA Brain 50 ALAAILTRL Kidney, stomach, colon and rectum 51 ALMLQGVDL Esophagus 53 SSFGGLGGGSV Lung 54 YLDAMMNEA Brain, colon, rectum, liver and ovary 58 GLAAFKAFL Lung, kidney and liver 60 YLEEDVYQL Lung, kidney, colon, rectum and breast 64 FLVSNMLLAEA Prostate 65 YLYDSETKNA Kidney, colon, rectum, liver, ovary and esophagus 66 ALLSGLREA Kidney, leukocytes and melanoma 67 KMFFLIDKV Brain and liver 68 KLLTEVHAA Lung, kidney, stomach, colon, rectum, liver, breast and ovary 69 VMAPFTMTI Lung, liver, prostate, ovary and esophagus n / ccnn / zznz / Ε / γΐΛΐ 70 FLVDGSWSV Lung, stomach, colon, rectum, ovary and esophagus 71 FLLDGSANV Lung, stomach, colon, rectum, liver, breast, ovary and esophagus 72 YVYQNNIYL Lung, stomach, colon, rectum, liver, breast, melanoma, ovary and esophagus 73 TLVAIVVGV Lung, kidney, brain, stomach, colon, rectum, liver, prostate, breast, ovary and esophagus 74 KIQEILTQV Lung, kidney, brain, stomach, colon, rectum, liver, leukocytes, ovary and esophagus 75 RLDDLKMTV Lung, kidney, colon , rectum, ovary and esophagus 76 RLLDSVSRL Lung, kidney, colon, rectum, liver and ovary 77 GLTDNIHLV Lung, kidney, colon, rectum, ovary and esophagus 78 TLSSIKVEV Lung, kidney, stomach, colon, rectum, prostate, breast and melanoma 79 VLAPRVLRA Lung, kidney, brain, colon, rectum and liver 81 AMSSKFFLV Lung, brain, stomach, colon, rectum, liver, prostate and esophagus 82 SISDVIAQV Lung, brain, colon, rectum, liver and prostate 83 FLIDSSEGV Lung, colon, rectum, breast, ovary and esophagus 84 NLLDLDYEL Lung, stomach, colon, rectum, breast, ovary and esophagus 85 TVAEVIQSV Lung and esophagus 86 SLLAQNTSWLL Lung, kidney, brain, stomach, colon, rectum, liver and melanoma n / ccnn / zznz / Ε / γΐΛΐ 87 LLLGSPAAA Brain n / ccnn / zznz / E / YiAi Table 4-2: Peptides according to the present invention and specific uses thereof in other proliferative diseases, especially in other types of cancer (amendment of Table 4). The table presents, like Table 4, a list of the selected peptides that in other types of tumor have been found overpresented (including the specific presentation) in more than 5% of the tumor samples analyzed, or presented in more than 5% of the tumor samples analyzed with a ratio of the geometric means to those of the normal tissues greater than 3. Overpresentation is defined as a higher presentation in the tumor sample than in the normal sample with greater presentation. The normal tissues in which the overpresentation was contrasted were: Adipose tissue, adrenal gland, blood cells, blood vessel, bone marrow, brain, cartilage, esophagus, eye, gallbladder, heart, kidney, large intestine, liver, lung, lymph node lymphatic, nerve, pancreas, parathyroid gland, peritoneum, pituitary gland, pleura, salivary gland, skeletal muscle, skin, small intestine, spleen, stomach, thymus, thyroid gland, trachea, ureter and urinary bladder. SEQ ID NO. Sequence Additional entities 3 ALLTFMEQV SCLC, breast cancer, melanoma, urinary bladder cancer, gallbladder cancer, bile duct cancer 4 SVDVSPPKV Melanoma, esophageal cancer 5 LLVDDSFLHTV SCLC, breast cancer, melanoma, esophageal cancer, uterine cancer, gallbladder cancer, bile duct cancer 6 VLISLKQAPLV Breast cancer, urinary bladder cancer, gallbladder cancer, bile duct cancer SEQ ID NO. Sequence Additional Entities 8 IVDDLTINL NSCLC, gastric cancer, melanoma, uterine cancer, gallbladder cancer, bile duct cancer, NHL 9 FLFDGSANLV SOLO, melanoma, ovarian cancer, urinary bladder cancer, gallbladder cancer, bile duct cancer 1 0 FLVDGSSAL SOLO, CRC, melanoma, esophageal cancer, urinary bladder cancer, gallbladder cancer, bile duct cancer 1 1 FLYKIIDEL SOLO, melanoma, urinary bladder cancer, gallbladder cancer biliary, bile duct cancer 12 FVSEIVDTV SOLO, gastric cancer, CRC, urinary bladder cancer, gallbladder cancer, bile duct cancer 13 LLAGQTYHV NSCLC, breast cancer, ovarian cancer, esophageal cancer, urinary bladder, gallbladder cancer, bile duct cancer 14 VLAKPGVISV Breast cancer, gallbladder cancer, bile duct cancer 1 5 SLANNVTSV Urinary bladder cancer, uterine cancer, gallbladder cancer, cancer bile duct cancer 16 APVNVTTEVKS V AML 19 HLAPETDEDDL Gallbladder cancer, bile duct cancer 20 RLAGDGVGAV Urinary bladder cancer 21 HLMDQPLSV Ovarian cancer, esophageal cancer, uterine cancer, gallbladder cancer, cancer n / ccnn / zznz / Ε / γΐΛΐ SEQ ID NO. Sequence Additional entities of the bile ducts 22 TLDGAAVNQV Esophageal cancer, uterine cancer, gallbladder cancer, bile duct cancer 23 SLSAFTLFL SCLC, breast cancer, melanoma, ovarian cancer, esophageal cancer, urinary bladder cancer , gallbladder cancer, bile duct cancer, NHL 24 GLLEELVTV SCLC, CRC, breast cancer, uterine cancer, gallbladder cancer, bile duct cancer 29 FLQEYLDAI Urinary bladder cancer 30 VVDEGPTGV SCLC, CRC , melanoma, urinary bladder cancer, uterine cancer, gallbladder cancer, bile duct cancer, NHL 34 MLMPVHFLL Breast cancer 37 GLLKKINSV Breast cancer, esophageal cancer, urinary bladder cancer, gallbladder cancer , bile duct cancer, ovarian cancer 38 NLVEKTPALV AML 39 TLLSNLEEA Urinary bladder cancer, uterine cancer, NHL 40 FILDSAETTTL SCLC, breast cancer, ovarian cancer, esophageal cancer 41 FLLDGSEGV SCLC, melanoma, urinary bladder cancer , gallbladder cancer, bile duct cancer 42 KLVDKSTEL SCLC, breast cancer, melanoma, gallbladder cancer, duct cancer n / ccnn / zznz / Ε / γΐΛΐ SEQ ID NO. Sequence Additional biliary entities 43 RLDQRVPQI SCLC, gallbladder cancer, bile duct cancer 44 VLLDKIKNLQV SCLC, ovarian cancer, esophageal cancer, urinary bladder cancer, gallbladder cancer, bile duct cancer, NHL 45 VADKIHSV Breast cancer, melanoma, esophageal cancer, urinary bladder cancer 46 TFAPVNVTTEVK SV Gallbladder cancer, bile duct cancer 47 KMDASLGNLFA Esophageal cancer, urinary bladder cancer 50 ALAAILTRL Uterine cancer, gallbladder cancer , bile duct cancer 51 ALMLQGVDL Breast cancer 53 SSFGGLGGGSV Breast cancer 54 VLLSEIEVA Melanoma, uterine cancer 55 YLDAMMNEA Prostate cancer, melanoma, urinary bladder cancer, gallbladder cancer, bile duct cancer 58 GLAAFKAFL SCLC , breast cancer, melanoma, ovarian cancer, esophageal cancer, uterine cancer, gallbladder cancer, bile duct cancer, NHL, ovarian cancer 60 YLEEDVYQL Melanoma, esophageal cancer, urinary bladder cancer, cancer uterus, gallbladder cancer, bile duct cancer, NHL 64 FLVSNMLLAEA Urinary bladder cancer 65 YLYDSETKNA SCLC, breast cancer, uterine cancer, gallbladder cancer, gallbladder cancer n / ccnn / zznz / Ε / γΐΛΐ SEQ ID NO. Sequence Additional entities bile ducts 66 ALLSGLREA Gastric cancer, breast cancer 67 KMFFLIDKV Breast cancer, melanoma, ovarian cancer, urinary bladder cancer, uterine cancer, gallbladder cancer, bile duct cancer, NHL, breast cancer ovary n / ccnn / zznz / Ε / γΐΛΐ NSCLC = non-small cell lung cancer, SCLC = small cell lung cancer, CRC = colorectal cancer, HCC = liver cancer, MCC = Merkel cell carcinoma, NHL = non-Hodgkin lymphoma, AML = acute myeloid leukemia, CLL = chronic lymphocytic leukemia. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 3, 4, 9, 10, 1 1, 12, 14, 15, 21, 23, 24, 30, 36, 40, 41, 42, 43, 44, 50, 53, 58, 60, 68, 69, 70 , 71, 72, 73, 74, 75, 76, 77, 78, 79, 81, 82, 83, 84, 85 and 86 for - in a preferred combined modality - the treatment of lung cancer. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 3, 4, 5, 15, 30, 45, 50, 58, 60, 65, 66, 68, 73, 74, 75, 76, 77, 78, 79 and 86 for - in a preferred combined modality - the treatment of kidney cancer. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 3, 5, 15, 30, 36, 39, 47, 55, 67, 73, 74, 79, 81, 82, 86 and 87 for - in a preferred combined modality - the treatment of brain cancer. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 3, 9, 11, 42, 43, 44, 50, 55, 60, 65, 68, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 81, 82, 83, 84 and 86 for - in a preferred combined modality - the treatment of colon cancer. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 3, 9, 11, 42, 43, 44, 50, 55, 60, 65, 68, 70, 71, 72, 73 74, 75, 76, 77, 78, 79, 81, 82, 83, 84 and 86 for - in a preferred combined modality - the treatment of rectal cancer. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 3, 8, 9, 12, 15, 41, 42, 43, 51, 65, 69, 70, 71, 7273, 74, 75, 77, 81, 83, 84 and 85 for - in a preferred combined embodiment - the treatment of esophageal cancer. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 4, 5, 15, 44, 66, 72, 78, and 86 for - in a preferred combined modality - the treatment of melanoma. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 5, 15, 24, 30, 41, 55, 65, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 83 and 84 for - in a preferred combined modality - the treatment of cancer of ovary. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 9, 10, 1 1, 12, 41, 43, 60, 71, 72, 73, 78, 83 and 84 for - in a preferred combined modality - the treatment of breast cancer. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 5, 30, 44, 55, 58, 65, 67, 68, 69, 71, 72, 73, 74, 76, 79, 81, 82, 85 and 86 for - in a preferred combined modality - the treatment of liver cancer . Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 10, 15, 24, 30, 34, 44, 45, 50, 68, 70, 71, 72, 73, 74, 78, 81, 84 and 86 for - in a preferred combined modality - the treatment of gastric cancer. n / ccnn / zznz / E / YiAi Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 23, 39, 64, 69, 73, 78, 81 and 82 for - in a preferred combined modality - the treatment of prostate cancer. Thus, another aspect of the present invention refers to the use of at least one peptide according to the claim selected from SEQ ID NO. 16, 30, 66 and 74 for - in a preferred combined modality - the treatment of leukocytic cancer. The present invention further relates to peptides according to the present invention that have the ability to bind to a molecule of the human major histocompatibility complex (MHC) class I or - in a longer form -, as a length variant , to an MHC class II molecule. The present invention further relates to peptides according to the present invention wherein each of said peptides consists essentially of an amino acid sequence according to SEQ ID NO. 1 to SEQ ID NO. 67. The present invention further relates to peptides according to the present invention, wherein said peptides are modified and / or include non-peptide bonds. The present invention further relates to the peptides according to the present invention, wherein said peptide is part of a fusion protein, in particular fused with the N-terminal amino acids of the invariant chain associated with the HLA-DR antigen (l! ), or fused with (or integrated into the sequence of) an antibody, such as, for example, an antibody that is specific for dendritic cells. The present invention further relates to a nucleic acid, which encodes the peptides according to the present invention. The present invention further relates to the nucleic acid according to the present invention which is DNA, cDNA, PNA, RNA or combinations of the above. The present invention further relates to an expression vector capable of expressing and / or that expresses a nucleic acid according to the present invention. The present invention further relates to an n / ccnn / zznz / E / YiAi peptide according to the present invention, a nucleic acid according to the present invention or an expression vector according to the present invention for use in the treatment of diseases and in medicine, specifically for the treatment of cancer. The present invention also relates to antibodies specifically directed against the peptides according to the present invention or against complexes formed by said peptides with the MHC, as well as methods for preparing them. The present invention also relates to T lymphocyte receptors (TCR), specifically soluble TCRs (TCRs) and TCR cloned and synthesized in autologous or allogeneic T lymphocytes, and to methods for producing them, as well as to NK cells or other type of cells that carry said TCR or cross-react with said TCR. Antibodies and TCRs constitute additional embodiments of the immunotherapeutic use of the peptides according to the present invention. The present invention further relates to a host cell containing a nucleic acid according to the present invention or an expression vector as described above. The present invention further relates to a host cell according to the present invention which is an antigen-presenting cell, and preferably is a dendritic cell. The present invention further relates to a method for producing a peptide according to the present invention, which comprises culturing the host cell according to the present invention and isolating the peptide from said host cell or its medium. of cultivation. The present invention further relates to the method according to the present invention wherein the antigen is loaded on MHC class I or II molecules expressed on the surface of a suitable antigen-presenting cell or an artificial antigen-presenting cell. by contacting a sufficient amount of antigen with the antigen-presenting cell. The present invention further relates to the method according to n / ccnn / zznz / E / YiAi with the present invention, wherein the antigen-presenting cell comprises an expression vector capable of expressing said peptide containing SEQ ID NO. 1 to SEO ID NO. 67, preferably SEQ ID NO. 1 to SEQ ID NO. 34, or a variant of said amino acid sequences. The present invention further relates to activated T lymphocytes, produced with the method according to the present invention, which selectively recognize a cell expressing a polypeptide comprising an amino acid sequence according to the present invention. The present invention further relates to a method of destroying target cells in a patient whose target cells aberrantly express a polypeptide comprising any of the amino acid sequences according to the present invention, the method comprising administering to the patient of an effective number of T lymphocytes produced in accordance with the present invention. The present invention also relates to the use as a medicine or in the preparation of a medicine of any peptide as described, of the nucleic acid according to the present invention, of the expression vector according to the present invention, of the cell according to the present invention, the activated T cell, the T cell receptor or the antibody or other molecules that bind to the peptide and / or the peptide-MHC complex according to the present invention. Preferably, said medicament is active against cancer. Preferably, said medicament is intended to serve as a cell therapy, as a vaccine or as a protein, or is based on a soluble TCR or an antibody. The present invention further relates to the use according to the present invention, wherein said cancer cells are pancreatic cancer, lung cancer, kidney cancer, brain cancer, colon or rectal cancer, esophageal cancer, breast cancer, ovarian cancer, gastric cancer, liver cancer, prostate cancer, melanoma and leukemias, and preferably pancreatic cancer cells. n / ccnn / zznz / E / YiAi The present invention also relates to biomarkers based on the peptides according to the present invention, here called "targets", which can be used for the diagnosis of cancer, preferably pancreatic cancer. The marker may be an overpresentation of the peptide or peptides in question, or the overexpression of the corresponding gene or genes. The markers could also be used to predict the probability of success of a treatment, preferably an immunotherapy, and more preferably an immunotherapy directed against the same target that is identified with the biomarker. For example, an antibody or a soluble TCR can be used to stain histological sections of the tumor to detect the presence of a peptide of interest bound in complex with an MHC. Optionally, the antibody may be endowed with another effector function, such as an immunostimulatory domain or a toxin. The present invention also relates to the use of these new targets in the context of cancer treatment. In the following detailed description of the underlying expression products (polypeptides) of the peptides according to the invention, applications against other types of cancer, both therapeutic and diagnostic, are disclosed. The ACAT2 gene encodes acetyl-CoA acetyltransferase 2, a thiolase involved in lipid metabolism. ACAT2 expression is upregulated in hepatocellular carcinoma (Song et al., 2006). ACAT2 expression has been linked to radioresistance in pancreatic cancer cell lines (Souchek et al., 2014). The ACTA1 gene encodes skeletal muscle alpha-actin, a member of the actin family, a group of highly conserved proteins involved in cell motility, structure, and integrity. ACTA1, a classical myoepithelial marker, was shown to be overexpressed in tumor-associated fibroblasts in urinary bladder cancer, oral squamous cell carcinoma, invasive breast cancer, gastric cancer, cholangiocarcinoma, and metastatic liver carcinoma, and contributes to epitheliomesenchymal transition. , to the formation of tumor stroma and to fibrosis n / ccnn / zznz / E / YiAi (Schulte et al., 2012; Franz et al., 2010; Kuroda et al., 2005; Nakayama et al., 2002; Terada et al., 1996). The ACTA2 gene encodes alpha smooth muscle actin, a member of the actin family, a group of highly conserved proteins involved in cell motility, structure, and integrity (RefSeq, 2002). Mononucleotide polymorphisms or copy number variations of the ACTA2 gene have been discovered in chronic lymphocytic leukemia, brain metastases from non-small cell lung cancer, and metastatic melanoma cell lines (Berndt et al., 2013; Lee et al. ., 2012; Dutton-Regester et al., 2012). From a functional point of view, high levels of ACTA2 expression were shown to be associated with the enhancement of invasion by tumor cells and the formation of metastasis (Kojima et al., 2014; Lee et al., 2013b; Tatenhorst et al. ., 2004). The ACTB gene encodes beta-actin, one of the main components of the contractile apparatus and one of the two cytoskeletal actins that are not found in muscle (RefSeq, 2002). ACTB was shown to be deregulated in liver cancer, melanoma, kidney cancer, colorectal cancer, gastric cancer, pancreatic cancer, esophageal cancer, lung cancer, breast cancer, prostate cancer, ovarian cancer, leukemia and lymphoma. Aberrant expression and polymerization of ACTB and the resulting changes in the cytoskeleton were shown to be linked to cancer invasiveness and metastasis ( Guo et al., 2013 ). The ACTBL2 gene encodes kappa actin, a member of the actin family, a group of highly conserved proteins involved in cell motility, structure, and integrity (RefSeq, 2002). Increased expression of ACTBL2 has been observed in hepatocellular carcinoma and hepatoma cells, where it altered cell growth properties and contributed to a negative postoperative prognosis ( Chang et al., 2006 ; Chang et al., 2011 ). The ACTC1 gene encodes cardiac muscle alpha 1 actin, one of the main components of the contractile apparatus of n / ccnn / zznz / E / YiAi cardiomyocytes (RefSeq, 2002). Alteration of ACTC1 expression has been described in bladder cancer, in non-small cell lung cancer cells treated with paclitaxel, and in chemoresistant ovarian cancer (Zaravinos et al., 2011; Che et al., 2013; Pan et al., 2009). Likewise, ACTC1 could serve as a diagnostic marker for prostate cancer and rhabdomyosarcoma (Huang et al., 2010; Clement et al., 2003). The ACTG1 gene encodes gamma actin 1, a cytoplasmic actin present in non-muscle cells, which mediates internal cell motility (RefSeq, 2002). ACTG1 was shown to be overexpressed in small cell lung cancer and elosteosarcoma, and downregulated in epithelial ovarian cancer (Li et al., 2010; Jeong et al., 2011; Chow et al., 2010). Alterations in ACTH1 levels have been described that promote invasion and metastasis formation in different types of cancer cells. In colon cancer and hepatocellular carcinoma cells, overexpression of ACTG1 enhances migration and invasion, while in melanoma and salivary gland adenocarcinoma cells, downregulation of ACTG1 is associated with this phenotype (Simiczyjew et al. al., 2014; Luo et al., 2014; Zhang et al., 2006; Gutgemann et al., 2001; Suzuki et al., 1998). The ACTG2 gene encodes gamma actin 2, a smooth muscle actin present in enteric tissues and mediating internal cell motility (RefSeq, 2002). The possible role of ACTG2 as a biomarker for the diagnosis of prostate cancer is debated, since its positive regulation has been demonstrated in transdifferentiated prosthetic stromal cells (Fillmore et al., 2014; Untergasser et al., 2005). Regarding chemotherapy, ACTG2 was shown to be upregulated following treatment with paclitaxel in laryngeal cancer cells, it seems to be involved in resistance to cisplatin in breast cancer cells and its positive correlation has been demonstrated with sensitivity of colorectal cancer with liver metastases to the FOLFOX4 regimen (Xu et al., 2013; Watson et al., 2007; Lu et al., 2013b). The ADAM8 gene encodes the n / ccnn / zznz / E / YiAi metallopeptidase domain protein ADAM 8, a member of the family of disintegrin and metalloprotease domain proteins that mediate cell-cell and cell-cell interactions. extracellular matrix (RefSeq, 2002). ADAM8 overexpression in pancreatic cancer is associated with increased migration and invasiveness in pancreatic duct adenocarcinoma cells (Schlomann et al., 2015). ADAM8 mediates tumor cell migration and invasion in lung cancer, renal cell carcinoma, and brain cancers (Mochizuki and Okada, 2007). The AEBP1 gene encodes adipocyte stimulator binding protein 1, a carboxypeptidase A that may function as a transcriptional corepressor important for adipogenesis and smooth myocyte differentiation (RefSeq, 2002). AEBP1 is upregulated in melanoma and contributes to acquired resistance against inhibition of the B1 homolog of the murine sarcoma viral oncogene v-raf (BRAF) mutant (Hu et al!., 2013). AEBP1 was shown to be upregulated in most primary glioblastomas (Reddy et al., 2008). The AHNAK2 gene encodes the structural protein AHNAK nucleoprotein 2 (Marg et al., 2010). AHNAK2 is an important element of the non-classical secretion pathway of fibroblast growth factor 1 (FGF1), a factor involved in tumor growth and invasion (Kirov et al., 201 5). The ANKH gene encodes the progressive ankylosis homolog (mouse) Z inorganic pyrophosphate transport regulator ANKH, a multi-pass transmembrane protein that controls pyrophosphate levels (RefSeq, 2002). The ANO1 gene encodes anoctamine 1, a calcium-activated chloride channel linked to small intestinal sarcoma and oral cancer (RefSeq, 2002). ANO1 was shown to be amplified in esophageal squamous cell cancer (ESCC), gastrointestinal stromal tumor (GIST), head and neck squamous cell carcinoma (HNSCC), as well as pancreatic and breast cancer (Qu et al. , 2014). n / ccnn / zznz / E / YiAi The APOB gene encodes apolipoprotein B, the main apolipoprotein of chylomicrons and low-density lipoproteins (LDH) (RefSeq, 2002). In alpha-fetoprotein-negative, HBV-linked hepatocellular carcinoma (HCC), APOB has been found to be one of 14 differentially expressed proteins that could be associated with the progression of such cancer (He et al., 2014). In advanced breast cancer, APOB has been found to be one of the 6 differentially expressed proteins that could predict response to neoadjuvant chemotherapy and recurrence-free survival of patients (Hyung et al., 2011). The ASPHD1 gene encodes aspartate beta-hydroxylase domain-carrying protein 1. ASPHD1 is located on chromosome 1 6p11. 2 (RefSeq, 2002). The ATM gene encodes the mutated ataxiatelangiectasia protein, a member of the PI3 / PI4 kinase family and the master controller of cell cycle checkpoint signaling pathways that are necessary to activate the cellular response to DNA damage. and maintain genome stability (RefSeq, 2002). ATM is an oncosuppressant that was shown to be frequently mutated in a wide range of human cancers such as lung, colorectal, breast, and hematopoietic neoplasms (Weber and Ryan, 2014). The ATP5B gene encodes the H+ transporter ATP synthase beta polypeptide of the mitochondrial complex F1, the beta subunit of the catalytic center of mitochondrial ATP synthase (RefSeq, 2002). ATP5B gene expression was significantly higher in colorectal cancer tissues than in healthy tissues (Geyik et al., 2014). Downregulation of ATP5B in tumor tissues is closely related to metastasis, invasion, and poor prognosis in gallbladder cancer (Sun et al., 2015b). The ATP5L gene encodes the G subunit of ATP synthase, a H + transporter, of the mitochondrial complex Fo, the membrane-inserted component of mitochondrial ATP-synthase, which comprises the proton channel (RefSeq, 2002). The ATP5L2 gene encodes the G2 subunit of the ATP synthase, H + transporter, of the mitochondrial complex Fo, the membrane-inserted n / ccnn / zznz / E / YiAi component of the mitochondrial ATP-synthase, which comprises the proton channel (RefSeq, 2002). The BACE2 gene encodes the beta-dot amyloid precursor protein (APP) hydrolytic enzyme 2, an integral membrane glycoprotein and aspartate protease. BACE2 cleaves the amyloid precursor protein into the amyloid beta peptide (RefSeq, 2002). BACE2 mediates the function of pancreatic beta cells (Vassar et al., 201 4). The CCNB1 gene encodes cyclin B1, a regulatory protein involved in mitosis (RefSeq, 2002). CCNB1 is a known tumor antigen whose overexpression has been described in breast, head and neck, prostate, colorectal, lung and liver cancer (Egloff et al., 2006). The CEACAM6 gene encodes the cell adhesion molecule related to carcinoembryonic antigen 6 (nonspecific cross-reactive antigen), belonging to the CEACAM family of tumor markers (RefSeq, 2002). CEACAM6 is upregulated in gastric tumors (Yasui et al., 2004). CEACAM6 is a candidate breast cancer tumor antigen (Sood, 2010). The CLTA gene encodes the clathrin A light chain, a structural component of coated pits with a regulatory function (RefSeq, 2002). The CLTA gene presents an alternative splicing variant in glioma (Cheung et al., 2008). The CLTB gene encodes clathrin B light chain, a structural component of coated pits with regulatory function (RefSeq, 2002). The CLU gene encodes a secreted chaperone that could be involved in various basic biological phenomena such as cell death, tumor progression and neurodegenerative disorders (RefSeq, 2002). Its role in oncogenesis seems to be ambivalent since in normal cells and in the early stages of carcinogenesis, CLU would inhibit tumor progression, while in advanced neoplasia it seems to confer substantially greater survival to the tumor by suppressing many therapeutic stressors and enhancing the metastasis. CLU has been shown to play a critical role in n / ccnn / zznz / E / YiAi prostate cancer pathogenesis by regulating the aggressive behavior of human clear renal cell carcinoma cells through modulation of prostate cancer signaling. ERK1 / 2 and MMP-9 expression and confer treatment resistance in advanced stages of lung cancer (Trougakos, 2013; Pánico et al., 2009; Takeuchi et al., 2014; Wang et al., 2014b ). The COL12A1 gene encodes the alpha chain of collagen type . COL12A1 was shown to be overexpressed in drug-resistant variants of ovarian cancer cell lines (Januchowski et al., 2014). In colorectal cancer, COL12A1 was shown to be overexpressed in the desmoplastic stroma surrounding cancer-associated fibroblasts, as well as in cancer cells lining the invasion front (Karagiannis et al., 2012). The COL6A3 gene encodes the alpha-3 chain of type VI collagen, a filamentous, pearly collagen present in most connective tissues, which plays an important role in the organization of matrix components (RefSeq, 2002). It has been described that COL6A3 expression is high in pancreatic, colon and gastric cancer, mucoepidermoid carcinomas and ovarian cancer. Cancer-associated transcript variants encompassing exons 3, 4, and 6 have been detected in colon, bladder, prostate, and pancreatic cancer (Arafat et al., 2011; Smith et al., 2009; Yang et al., 2007; Xie et al., 2014; Leivo et al., 2005; ShermanBaust et al., 2003; Gardina et al., 2006; Thorsen et al., 2008). In ovarian cancer, COL6A3 levels were correlated with a higher tumor grade and, in pancreatic cancer, it has been shown that it could serve as a serum biomarker for diagnosis (Sherman-Baust et al., 2003; Kang et al. ., 2014). The DCBLD2 gene encodes discoidin or LCCL and CUB domain-bearing protein 2, also called endothelium- and smooth muscle-derived neuropilin-like protein (ESDN), a coreceptor transmembrane protein (RefSeq, 2002). DCBLD2 was shown to be upregulated in glioblastomas and head and neck cancer and is required for EGFR-stimulated oncogenesis (Feng et al., 2014). Furthermore, DCBLD2 is also upregulated in substrains and tissue samples of highly metastatic lung cancer (Koshikawa et al., 2002). On the other hand, its expression is silenced in gastric cancer due to hypermethylation of its promoter (Kim et al., 2008). The DUSP14 gene, dual-specificity phosphatase 14, can dephosphorylate both tyrosine and serine / threonine residues and is involved in the inactivation of MAP kinase signaling (RefSeq, 2002). SNPs in the DUSP14 gene are linked to altered melanoma risk (Yang et al., 2014a; Liu et al., 2013a). The EEF1A1 gene encodes a form of the alpha subunit of the elongation factor-1 complex, which is responsible for the enzymatic incorporation of aminoacyl-tRNAs into the ribosome (RefSeq, 2002). EEF1A1 has been shown to be upregulated in various tumor entities, such as colorectal cancer, ovarian cancer, gastric cancer, prostate cancer, glioblastoma and squamous cell carcinoma, and has been described as a possible serum biomarker of prostate cancer (Matassa et al., 2013; Vui-Kee et al., 2012; Lim et al., 2011; Kuramitsu etal., 2010; Kido etal., 2010; Scrideli et al., 2008; Qí et al. ., 2005; Rehman et al., 2012). EEF1A1 inhibits apoptosis through interaction with p53 and p73, promotes proliferation through transcriptional repression of the cell cycle inhibitor p21, and participates in the regulation of the epitheliomese n chemical transition (Blanch et al., 2013; Choi et al., 2009; Hussey et al., 2011). The EEF1A1P5 gene encodes the eukaryotic translation elongation factor 1 alpha 1 pseudogene 5, which is located on chromosome 9q34. 13 (RefSeq, 2002). The FAMC3 gene belongs to the family with sequence similarity 3 (FAM3) and encodes a secreted protein carrying a GG domain. A change in expression of this protein has been observed in cells derived from pancreatic cancer (RefSeq, 2002). In melanoma, FAMC3 has been identified as a candidate biomarker of autophagy, an important survival mechanism of tumor cells (Zou et al., 2002; Kraya et al., 2015). . FAMC3 plays an essential role in epithelial-mesenchymal transition that correlates with malignancy and metastatic progression of tumors, as well as short survival, especially in hepatocellular cancer, colorectal cancer, and lung and breast tumors ( Csiszar et al., 2014; Gao et al., 2014c; Song et al., 2014; Chaudhury et al., 2010; Lahsnig et al., 2009). The FAP gene encodes a transmembrane serine protease that is selectively expressed in reactive stromal fibroblasts of epithelial tumors (cancer-associated fibroblasts or CAFs), in granulation tissue of healing wounds, and in malignant cells of bone and soft tissue sarcomas (RefSeq, 2002). FAP plays an important role in tumor growth and metastasis due to its intervention in cell adhesion, migration processes and extracellular matrix (ECM) remodeling (Jacob et al., 2012). Overexpression of FAP is correlated with a poor prognosis, advanced tumor staging, metastasis formation and invasive potential in various types of cancer, such as colon cancer, esophageal squamous cell carcinoma, pancreatic adenocarcinoma, glioblastoma, osteosarcoma, ovarian cancer and breast cancer (Wikberg et al., 2013; Kashyap et al., 2009; Cohén et al., 2008; Mentlein et al., 2011; Yuan et al., 2013; Zhang et al. , 2011; Ariga et al., 2001). The FKBP10 gene encodes FK506-binding protein 10, which belongs to the FKBP-type peptidiI-proIiI cis / trans isomerase family. The FKBP10 gene product is located in the endoplasmic reticulum and acts as a molecular chaperone (RefSeq, 2002). FKBP10 has been identified as a new gene involved in the acquisition and maintenance of the adriamycin-resistant phenotype in leukemic cells (Sun et al., 2014). FKBP10 has been linked to colorectal cancer through its upregulation (Olesen et al., 2005). In contrast, its decreased expression appears to be characteristic of ovarian epithelial carcinomas (Quinn et al., 2013). n / ccnn / zznz / Ε / γΐΛΐ The FLNA gene encodes filamin A, an actin-binding protein that cross-links actin filaments and attaches them to membrane glycoproteins. The encoded protein intervenes in the remodeling of the cytoskeleton that causes changes in the morphology and migration of the cell, and interacts with integrins, transmembrane receptor complexes, and second messengers (RefSeq, 2002). Depending on its location within the cell, filamin has an ambivalent role in cancer: In the cytoplasm, filamin A acts in several growth signaling pathways, in addition to intervening in pathways related to cell migration and adhesion. In short, its overexpression exerts a tumor-promoting effect. Unlike the entire filamin A, the C-terminal fragment, which is released with proteolysis of the protein, is located in the nucleus, where it interacts with transcription factors suppressing tumor growth and metastasis (Savoy and Ghosh, 201 3 ). The GGA1 gene encodes a member of the ARF-binding protein (GGA) family, which carries the ear domain of gamma-adaptin, located in the Golgi apparatus. Members of this family are ubiquitous coat proteins that regulate protein trafficking between the trans-Golgi network and the lysosome (RefSeq, 2002). The HBB gene encodes the beta chain of human hemoglobin, the oxygen-transporting ferric metalloprotein of the erythrocyte (RefSeq, 2002). The ability of breast cancer to generate bone and visceral metastases is a clear indicator of the poor clinical outcome compared to cases of this type of cancer where metastases are restricted to bone tissue. The increased expression of HBB in bone metastases is related to its ability to spread rapidly to other organs (Capulli et al., 2012). It has been found that HBB is overexpressed in cervical carcinoma tissue. Ectopic expression of HBB in cervical cancer cells abolished oxidative stress and improved cell viability (Li et al., 2013). The HBD gene encodes the delta chain of human hemoglobin, the oxygen-transporting ferric metalloprotein of the erythrocyte. n / ccnn / zznz / E / YiAi hemoglobin A2 is made up of two alpha chains and two delta chains, which with HbF constitutes 3% of adult hemoglobin (RefSeq, 2002). The HKDC1 gene encodes hexokinase domain carrier protein 1, which displays hexokinase activity in vitro (Guo et al., 2015). Thanks to a new method to discover possible therapeutic targets from heterogeneous data, among other known targets, HKDC1 emerged as a new such target in lung cancer (Li and Huang, 2014). The HSPD1 gene encodes the 60 kDa mitochondrial heat shock protein 1, belonging to the chaperonin family, which is essential for the folding and assembly of newly imported proteins into the mitochondria and could act as a signaling molecule in the system. innate immune system (RefSeq, 2002). Although HSPD1 is considered a protein inside the mitochondria, it has also been found in the cytosol, in the cell membrane, in vesicles, on the cell surface, in the extracellular space and in the blood. Since HSPD1 levels in the cytosol increase or decrease in various organs during carcinogenesis, this protein may serve as a biomarker for the diagnosis and prognosis of preneoplastic and neoplastic lesions. Furthermore, some recently discovered functions of HSPD1 are linked to carcinogenicity, specifically the survival and proliferation of tumor cells, which is why it has been intensely debated as a promising target for antitumor treatment (Pace et al., 2013; Nakamura and Minegishi, 2013; Cappello et al., 2013; Cappello et al., 2011; Cappello et al., 2008). The HYOU1 gene encodes hypoxia-upregulated protein 1, better known as glucose-regulated protein 170 kDa (GRP170), which belongs to the heat shock protein 70 family. HYOU1 expression is stimulated in stress conditions generated by hypoxia and leads to the accumulation of the protein in the endoplasmic reticulum. The protein encoded by HYOU1 is believed to play an important role in protein folding and secretion in the endoplasmic reticulum n / ccnn / zznz / Ε / γΐΛΐ (RefSeq, 2002). The activity of the HYOU1 protein localized within the cell has been shown to improve the survival of cancer cells during tumor progression or metastasis. The HYOU1 protein located outside the cell plays an essential role in generating the antitumor immune response by facilitating the release of tumor antigens for cross-presentation (Fu and Lee, 2006; Wang et al., 2014a). The HYOU1 protein has been used in cancer immunotherapy and has demonstrated a positive immunomodulatory effect (Yu ef al., 2013; Chen et al., 2013a; Yuan et al., 2012; Wang and Subjeck, 2013). In prostate cancer cells, deletion of HYOU1 revealed an antitumor effect (Miyagi et al., 2001). The IFT88 gene encodes a member of the tetratricopeptide repeat (TPR) family (RefSeq, 2002). In mitosis, IFT88 is part of a complex governed by dynein 1 that transports peripheral microtubule bundles to the spindle poles to ensure proper spindle orientation. Deletion of IFT88 causes mitotic defects in human cultured cells (Delaval et al., 2011). The loss of gene expression of IFT88 (also called Tg737) leads to the proliferation of hepatic stem cells (oval cells) and therefore acts as an oncosuppressor gene for liver neoplasia (Isfort et al., 1997). In 2012, a mutation was discovered that is responsible for a new form of ciliopathy and anosmia in humans that has been remedied in mice with gene therapy using adenoviral vectors (Mclntyre et al., 2012). The IGF2BP3 gene encodes insulinoid growth factor II mRNA binding protein 3, an oncofetal protein, which represses the translation of insulinoid growth factor II (RefSeq, 2002). Various studies have shown that IGF2BP3 acts in several important aspects of cellular function, such as cell polarization, migration, morphology, metabolism, proliferation and differentiation. In vitro studies have shown that IGF2BP3 promotes cell proliferation, adhesion and invasion. Furthermore, its relationship with aggressive and advanced tumors has been demonstrated (Bell et al., 2013; Gong et al., 2014). Overexpression of n / ccnn / zznz / Ε / γΐΛΐ IGF2BP3 has been described in numerous types of tumors as related to a poor prognosis, advanced tumor stage and metastasis, such as neuroblastoma, colorectal carcinoma, intrahepatic cholangiocarcinoma, hepatocellular carcinoma, prostate cancer and prostate cancer. kidney cells (Bell et al., 2013; Findeis-Hosey and Xu, 2012; Hu et al., 2014; Szarvas et al., 2014; Jeng et al., 2009; Chen et al., 2011; Chen et al., 2011; , 2013b; Hoffmann et al., 2008; Lin et al., 2013b; Yuan et al., 2009). The ITGB4 gene encodes a protein from the integrin family. Integrins are heterodimers composed of alpha and beta subunits that are non-covalently linked to transmembrane glycoprotein receptors. They mediate adhesion between cell and matrix and between one cell and another, and transduce signals that regulate gene expression and cell growth (RefSeq, 2002). ITGB4 (also called CD104) tends to be associated with the alpha 6 subunit and is likely to play an essential role in the biology of several invasive carcinomas such as esophageal squamous cell carcinoma, and bladder or ovarian carcinoma (Kwon et al. , 2013; Pereira et al., 2014; Chen et al., 2014b). A mononucleotide polymorphism of ITGB4 appears to influence tumor aggressiveness and survival, and could have prognostic value for patients with breast cancer (Brendle et al., 2008). The KCNK6 gene encodes one of the superfamily members of potassium channel proteins that contain two pore-forming P domains. This channel protein, considered an open rectifier, is widely expressed. It is stimulated by arachidonic acid, and inhibited by internal acidification and volatile anesthetics (RefSeq, 2002). The KCNK6 (also called K2P6. 1) along with the K2P1. 1, K2P3. 1, K2P5. 1, K2P6. 1, K2P7. 1 and K2P10. 1 exhibit significant down-expression in various cancer types as judged by a review of the online cancer microarray database Oncomine (www.oncomine.org) (Williams et al., 2013). The KCNN3 gene belongs to the KCNN family of potassium channels. It encodes an integral membrane protein that forms a voltage-independent calcium-activated channel n / ccnn / zznz / Ε / γΐΛΐ, which presumably regulates neuronal excitability by contributing to the slow component of postsynaptic hyperpolarization (RefSeq, 2002). The expression of KCNN3 (also called TASK-1) is downregulated by 1 7beta-estradiol in mouse neuroblastoma N2A cells and enhances cell proliferation (Hao et al., 2014). The expression of KCNN3 appeared upregulated by exposure of an organotypic breast cancer culture to 1,25-dihydroxy vitamin D (3) at physiological and supraphysiological concentrations (Milani et al., 2013). KCNN3 (also called K2P3.1), along with K2P1.1 and K2P12.1, appeared overexpressed in various cancer types in a screening of the online cancer microarray database Oncomine (www.oncomine.org). (Williams et al., 2013). The KDM1A gene (also called LSD1) encodes a nuclear protein containing a SWIRM domain, a FAD-binding motif, and an amino oxidase domain. This protein is a component of several histone deacetylase complexes, although it silences genes by acting as a histone demethylase (RefSeq, 2002). Overexpression of KDM1A promotes tumor cell proliferation, migration and invasion, and has been associated with poor prognosis in non-small cell lung cancer and hepatocellular carcinoma (Lv et al., 2012; Zhao et al. , 2013). Elevated KDM1A expression correlates with prostate cancer recurrence and increased VEGF-A expression (Kashyap et al., 2013). Inhibition of KDM1A with a combination of trichostatin A (TSA) and 5-aza-2'-deoxycytidine (decitabine) suppresses the oncogenicity of the ovarian cancer ascitic fluid cell line SKOV3 (Meng et al., 2013) . The KIF26B gene encodes a member of the kinesin protein superfamily (KIF) that is essential for kidney development. KIF26B expression is restricted to the metanephric mesenchyme, and its transcription is regulated by the zinc finger transcriptional regulator SalH (Terabayashi et al., 2012). Elevated expression of KIF26B in breast cancer is linked to poor prognosis (Wang et al., 2013b). Upregulation of KIF26B has been significantly correlated with tumor size when analyzing pairs of colorectal tumor tissue and adjacent normal mucosa. KIF26B plays an important role in colorectal carcinogenesis and acts as a new prognostic indicator and a possible therapeutic target for colorectal cancer (Wang et al., 2015). The KRT19 gene encodes a member of the keratin family. Keratins are proteins of the intermediate filaments responsible for the structural integrity of epithelial cells and are in turn divided into cytokeratins and hair keratins. KRT19 is specifically expressed in the periderm, the transient surface layer that surrounds the epidermis during development (RefSeq, 2002). The expression of KRT19 in tumor cells was shown to be a prognostic marker for several tumor entities such as breast, lung, ovarian and hepatocellular cancer (Skondra et al., 2014; Gao et al., 2014b; Liu et al., 2013b; Lee et al., 2013a). KRT19 has been shown to be an independent prognostic factor for pancreatic neuroendocrine tumors, especially insulin-negative tumors. KRT19-positive tumors are associated with poor outcome regardless of established pathological parameters such as size, lymphovascular invasion, and necrosis (Jain et al., 2010). The KRT7 gene encodes a member of the keratin gene family. Type II cytokeratins consist of basic or neutral proteins that are arranged in pairs of heterotypic keratin chains that are co-expressed during the differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in simple epithelia lining the cavities of internal organs and in glandular ducts and blood vessels (RefSeq, 2002). KRT7 is used in immunohistochemistry as a differentiator between various phenotypes and as a biomarker for the prognosis of certain types of cancer such as renal cell carcinoma, ovarian carcinoma, epithelial skin tumor, etc. (Kuroda et al., 2013; McCIuggage and Young, 2005; Alhumaidi, 2012). The LAMC2 gene belongs to the laminin family, an n / ccnn / zznz / E / YiAi family of extracellular matrix glycoproteins. Laminins are the main constituent of basement membranes, apart from collagen. They have been implicated in a wide variety of biological processes such as cell adhesion, differentiation, migration and signaling, neurite outgrowth and metastasis. LAMC2 encodes a protein that is expressed in various fetal tissues and is specifically localized in epithelial cells of the skin, lung and kidney (RefSeq, 2002). LAMC2 is highly expressed in anaplastic thyroid carcinoma and is associated with tumor progression, migration, and invasion by modulating EGFR signaling ( Garg et al., 2014 ). LAMC2 expression predicted a more negative prognosis in patients with stage II colorectal cancer (Kevans et al., 2011). The expression of LAMC2, along with that of three other biomarkers, has been linked to the presence of lymph node metastasis in patients with oral squamous cell carcinoma (Zanaruddin et al., 2013). The LUM gene encodes a member of the small leucine-rich proteoglycan (SLRP) family, which includes decorin, biglucan, fibromodulin, keratocan, epifican, and osteoglycin. Lumican is the major keratan sulfate proteoglycan of the cornea, although it was also shown in interstitial collagen matrices throughout the body. Lumican could regulate collagen fibril organization and circumferential growth, corneal transparency, and epithelial cell migration and tissue repair (RefSeq, 2002). The LUM protein was shown to be upregulated in many tumor tissues such as breast, colorectal, and pancreatic cancer compared to normal tissue, and is associated with higher tumor grade and poor outcome. However, extracellular lumican inhibits the growth of pancreatic cancer cells and is linked to prolonged survival after surgical removal (Leygue et al., 1998; Seya et al., 2006; Ishiwata et al., 2007; L ¡ et al., 2014). LUM and other genes related to extracellular matrix integrity (DCN and DPT) are differentially expressed and could serve as biomarkers of recurrent and metastatic giant cell bone tumor (Lieveld et al., 2014). LUM was shown to be downregulated n / ccnn / zznz / E / YiAi in variants of the A2780 ovarian cancer cell line that are resistant to cisplatin, doxorubicin, topotecan and paclitaxel (Januchowski et al., 2014). . The MAP4 gene encodes an important non-neuronal microtubule-associated protein, which promotes microtubule assembly and counteracts catastrophic microtubule destabilization that occurs in interphase. Phosphorylation of this protein affects the properties of microtubules and influences cell cycle progression (RefSeq, 2002). Elevated levels of MAP4 have been shown to positively correlate with grade in bladder cancer, while phosphorylation of the protein by protein kinase A reduces migration and invasion of bladder tumor cells (Ou et al., 2014). A study in patients with non-small cell lung cancer described an increased ratio of MAP4 to stathmin mRNA in tumor samples compared to normal samples, indicating that this ratio could serve as a biomarker for lung cancer. non-small cell lung (Cucchiarelli et al., 2008). MAP4 levels, which are negatively regulated by the oncosuppressor p53, influence the efficacy of microtubule-targeting agents. High levels enhance the effect of drugs that stabilize microtubules (taxanes) and reduce that of drugs that destabilize them (vinca alkaloids), while low levels of MAP4 exert the opposite effect (Hait and Yang, 2006; Galmarini et al., 2003; Zhang et al., 1999). The MMP7 gene encodes an enzyme that degrades proteoglycans, fibronectin, elastin, and casein, and which differs from most members of the MMP family by lacking the conserved C-terminal protein domain. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of the extracellular matrix in normal physiological processes, such as embryonic development, reproduction and tissue remodeling, as well as in pathological processes, such as arthritis and metastasis (RefSeq, 2002). MMP7 was shown to be frequently overexpressed in human cancer tissue, including colorectal cancer, metastatic lung carcinoma, and gastric cancer, and is associated with tumor progression and metastasis formation (Li et al., 2006; Sun et al., 2015a; Han et al., 2015; Long et al., 2014). MMP7 has demonstrated important tumor-promoting actions, such as the degradation of extracellular matrix proteins, activation of tumor cell proliferation by increasing the bioavailability of insulin-like growth factor and heparin-bound epidermal growth factor, and the induction of apoptosis in cells adjacent to the tumor by cleavage of the membrane-bound Fas ligand (I et al., 2006). The MROH6 gene, also called C8orf73, is located on chromosome 8q24. 3 (RefSeq, 2002). The MX1 gene encodes a guanosine triphosphate (GTP) metabolizing protein that is activated by type I and type II interferons and participates in the cell's antiviral response (RefSeq, 2002). The role of MX1 in cancer has not yet been elucidated. On the one hand, MX1 expression correlates with prostate cancer, reduces metastasis formation and enhances sensitivity to docletaxel. Likewise, epigenetic repression of MX1 due to hypermethylation has been detected in head and neck squamous cell carcinoma, and that MX1 expression reduces cell motility and tumor invasion in prostate cancer and melanoma cell lines, all of which points to an oncosuppressive effect of MX1 (Brown et al., 2015; Calmon et al., 2009; Mushinski et al., 2009). On the other hand, a mononucleotide polymorphism of the MX1 gene is linked to prostate cancer and high expression of MX1 is associated with lymph node metastasis in colorectal cancer, which indicates that it has oncogenic properties (Croner et al., 2014; Glymph et al., 2013). The MXRA5 gene encodes one of the proteins associated with matrix remodeling, which contains 7 leucine-rich repeats and 12 perlecan-related immunoglobulin-like C2-type domains (RefSeq, 2002). A Chinese study identified MXRA5 as the second most frequently mutated gene in non-small cell lung cancer (Xiong et al., 2012). In colon cancer, it has been shown that MXRA5 is overexpressed and could serve as a biomarker for early diagnosis and omental metastasis (Zou et al., 2002; Wang et al., 2013a). The MYH9 gene encodes a conventional non-muscle myosin HA heavy chain that contains an IQ domain and a myosin head-like domain that mediates several important functions, including cytokinesis, cell motility, and maintenance of cell morphology. (RefSeq, 2002). High expression of MYH9 has been shown to be associated with a poor prognosis in esophageal squamous cell carcinoma and, in combination with annexin II and kindling-2, could serve as a predictive biomarker for overall and disease-free survival in such cancer (Xia et al., 2012; Cao et al., 2014). Mutations of the MYH9 gene have been discovered in human breast cancer samples and their differential expression in colon carcinoma (Ellis et al., 2012; Mu et al., 2013). In vitro and xenograft studies indicate that MYH9 promotes the growth and invasion of different tumor cell lines, such as breast cancer and non-small cell lung cancer cells (Robinson et al., 2013; Lin et al. ., 2013a; Lund et al., 2012; Derycke et al., 2011; Medjkane et al., 2009). The MYL12A gene encodes a non-sarcomeric myosin regulatory light chain, which regulates the contraction of smooth muscle and non-muscle cells (Amatschek et al., 2004; RefSeq, 2002). MYL12A phosphorylation has been described to promote tumor cell motility and invasion under in vitro conditions and in an animal model (Manning, Jr. et al., 2000; Kaneko et al., 2002; Khuon et al., 2010). Furthermore, MYL12A appears to regulate DNA damage repair and p53-induced apoptosis by sequestering the transcriptional regulator called antagonistic apoptosis transcription factor (Hopker et al., 2012a; Hopker et al., 2012b). The MYL12B gene encodes a non-muscle myosin II regulatory light chain (MYH9). MYL12B phosphorylation increases MgATPase activity and the assembly of myosin II filaments (RefSeq, 2002). The protein is upregulated in grade 3 ovarian cancer, and pharmacological blockade of MYL12B phosphorylation or activation reduces n / ccnn / zznz / E / YiAi migration and invasion of tumor cells under in vitro conditions, as well as such as the formation of metastases in an animal model of breast cancer. These data point to the prometastatic role of MYL12B (Lim et al., 2011; Menhofer et al., 2014; Zhang et al., 2013; Patel et al., 2012). The PARD3B gene encodes a protein that is located in the occlusion zones of epithelial cells and participates in the establishment of cell polarity (Izaki et al., 2005). A mononucleotide polymorphism of the PARD3B gene is significantly associated with drug hepatotoxicity in children with acute lymphoblastic leukemia or lymphoblastic lymphoma (Horinouchi et al., 2010). The PDIA6 gene (also called ERp5) encodes a protein disulfide isomerase resident in the endoplasmic reticulum (ER) that catalyzes the formation, reduction and isomerization of disulfide bonds in proteins, and is believed to be involved in the folding of linked proteins. by such links (RefSeq, 2002). Immunostaining of prosthetic tissue microarrays with PDIA6 showed higher immunoreactivity in premalignant lesions compared with nonmalignant epithelium (P < 0.0001, Mann-Whitney U test), and in tumors with high Gleason grade (4-5 ) versus low grade (2-3) (P < 0.05) (Glen et al., 2010). Elevated ERp5 / ADAM10 expression leads to MICA secretion and impairs recognition of NKG2D ligands in the nodal microenvironment of Hodgkin lymphoma. This leads to downmodulation of NKG2D expression on the surface of CD8 T cells and an ineffective antitumor response (Zocchi et al., 2012). The disulfide isomerase enzymes PDIA4 and PDIA6 mediate resistance against cisplatin-induced cell death in lung adenocarcinoma ( Horibe et al., 2014 ). The PIK3IP1 gene encodes phosphoinositide-3-kinase interacting protein 1, an inhibitor of PI3K (RefSeq, 2002). Downregulation of PIK3IP1 reinforces tumor growth in human T cell lymphoblastic lymphoma cells (Wong et al., 2014). PIK3IP1 is downregulated in hepatocellular carcinoma (HCC) and suppresses the development of this type of cancer (He et al., 2008). n / ccnn / zznz / Ε / γΐΛΐ The PLEC gene encodes plectin, a member of the plakin family, a protein involved in cross-linking and organization of the cytoskeleton and adhesion complexes (Bouameur et al., 2014). PLEC was shown to be overexpressed in colorectal adenocarcinoma, head and neck squamous cell carcinoma, and pancreatic cancer (Lee et al., 2004; Katada et al., 2012; Bausch et al., 2011). The POTEE gene encodes member E of the POTE ankyrin domain family, one of 13 paralogs belonging to the POTE gene family. POTE genes are believed to represent a new family of cancer-testis antigens. The biological function of the POTE gene family is not known in full detail yet, but some evidence suggests a proapoptotic role (Liu et al., 2009; Bera et al., 2006). POTEE is predominantly expressed in prostate, breast, colon, lung and ovarian cancer (Bera et al., 2006). One study described a strong link of POTEE with breast cancer using a combined transcriptomic and proteomic approach (Cine et al., 2014). The POTEE gene encodes member F of the POTE ankyrin domain family, one of 13 paralogs belonging to the POTE gene family. POTE genes are believed to represent a new family of cancer-testis antigens. The biological function of the POTE gene family is not known in full detail yet, but some evidence suggests a proapoptotic role (Liu et al., 2009; Bera et al., 2006). POTEF has been shown to induce apoptosis in Hela cells through a mitochondrial pathway (Liu et al., 2009). POTEF is predominantly expressed in prostate, breast, colon, lung and ovarian cancer (Bera et al., 2006). The POTEI gene is located on chromosome 2q21. 1 and encodes member I of the POTE ankyrin domain family, one of 13 paralogs belonging to the POTE gene family. The POTE genes are believed to represent a new family of cancertestis antigens. The biological function of the POTE gene family is not known in full detail yet, but some evidence suggests a proapoptotic role (Liu et al., 2009; Bera et al., 2006). POTEI is n / ccnn / zznz / Ε / γΐΛΐ predominantly expressed in prostate, breast, colon, lung and ovarian cancer (Bera et al., 2006). The POTEJ gene encodes the J member of the POTE ankyrin domain family, one of 13 paralogs belonging to the POTE gene family. POTE genes are believed to represent a new family of cancer-testis antigens. The biological function of the POTE gene family is not known in full detail yet, but some evidence suggests a proapoptotic role (Liu et al., 2009; Bera et al., 2006). POTEJ is predominantly expressed in prostate, breast, colon, lung and ovarian cancer (Bera et al., 2006). The POTEKP gene encodes the POTE ankyrin domain family member K, a pseudogene that is located on chromosome 2q21. 1 (RefSeq, 2002). The POTEM gene encodes the POTE ankyrin domain family member M, one of 13 paralogs belonging to the POTE gene family. POTE genes are believed to represent a new family of cancer-testis antigens. The biological function of the POTE gene family is not known in full detail yet, but some evidence suggests a proapoptotic role (Liu et al., 2009; Bera et al., 2006). POTEM has been identified as a transcript specific to normal and malignant prosthetic tissue (Stolk et al., 2004). The PTRF gene encodes polymerase I and transcript releasing factor, a regulator of rRNA transcription that promotes dissociation of transcription complexes and polymerase I reinitiation into nascent rRNA transcripts (RefSeq, 2002). PTRF is downregulated in breast cancer cell lines and breast tumor tissue (Bai et al., 2012). It is a biomarker of non-small cell lung cancer (Gamez-Pozo et al., 2012). PTRF expression was shown to be downregulated in prostate cancer and its absence in prostate cancer cells significantly contributes to tumor progression and metastasis by promoting the angiogenic potential of cancer cells (Nassar et al., 2013). . The PUS7L gene encodes the pseudouridylate synthase homolog 7-like protein (S. cerevisiae), a protein with possible pseudouridine synthase activity. The PUS7L gene is located on chromosome 1 2q1 2 (RefSeq, 2002). The RAN gene encodes RAN, a member of the RAS oncogene family, a small GTP-binding protein that is involved in the translocation of RNA and proteins through the nuclear pore complex, in the control of DNA synthesis and in cell cycle progression, in the formation and organization of the microtubule network, and in androgen receptor activation (RefSeq, 2002). RAN is a key protein in metastatic cancer progression. RAN was shown to be overexpressed in various types of tumors, such as breast and kidney tumors (Matchett et al., 2014). The RANP1 gene encodes RAN, pseudogene 1 member of the RAS oncogene family, a pseudogene located on chromosome 6p21. 33 (RefSeq, 2002). The RASA4 gene encodes the RAS protein p21 activator 4, a Ca(2 + )-dependent RasGTPase-activating protein that inactivates the Ras-MAPK pathway in response to Ca(2 + ) (RefSeq, 2002). RASA4 is markedly amplified in primary cavity lymphoma (Roy et al., 2011). RASA4 is differentially expressed in endometrial adenocarcinoma compared to normal endometrium (Jeda et al., 2014). The RASA4B gene encodes the p21 RAS protein activator 4B, a Ca(2+)-dependent RasGTPase activating protein possibly involved in the regulation of the Ras-MAPK pathway (RefSeq, 2002). The RCN1 gene encodes reticulolocalbin 1, a calcium-binding protein endowed with an EF-hand domain to which this element binds, located in the lumen of the endoplasmic reticulum. RCN1 was shown to be associated with the plasma membrane in human endothelial and prostate cancer cell lines (RefSeq, 2002). RCN1 e was shown to be overexpressed in breast cancer (Amatschek et al., 2004). The RGS4 gene encodes G protein signaling regulator 4, a GTPase-activating protein (GAP) that acts on the alpha subunits of heterotrimeric G proteins (RefSeq, 2002). RGS4 revealed statistically significant n / ccnn / zznz / E / YiAi downregulation in liver metastases and at the tumor invasion front compared to the primary pancreatic tumor (Niedergethmann et al., 2007). RGS4 was shown to be highly overexpressed in thyroid carcinoma, although it is not expressed in normal human tissues (Nikolova et al., 2008). The RGS4 transcript has been detected in immortalized but non-cancerous ovarian surface epithelial cells at levels several thousand times higher than the expression observed in ovarian cancer cell lines (Hurst et al., 2009). The RPS6 gene encodes ribosomal protein S6, a cytoplasmic ribosomal protein that is a component of the 40S subunit of ribosomes. RPS6 could contribute to the control of cell growth and proliferation through the selective translation of certain classes of mRNA (RefSeq, 2002). RPS6 is a downstream target of mTOR and has been linked to multiple physiological and pathophysiological functions (Chen et al., 2014a). Phosphorylation of RPS6 attenuates DNA damage and oncosuppression during pancreatic cancer development (Khalaileh et al., 2013). The RPS8 gene encodes ribosomal protein S8, a cytoplasmic ribosomal protein that is a component of the 40S subunit of ribosomes. RPS8 expression is increased in colorectal tumors and colonic polyps compared to normal colonic mucosa from the same individual (RefSeq, 2002). Upregulation of RPS8 in patients with pancreatic duct adenocarcinoma correlates with short-term survival (Chen et al., 2015). The RPS8P10 gene encodes the ribosomal protein S8 pseudogene 10, a pseudogene located on chromosome 15q11. 2 (RefSeq, 2002). The SCG5 gene encodes secretogranin V (protein 7B2), a neuroendocrine secretory protein (Portela-Gomes et al., 2008). Duplication encompassing the 3' end of the SCG5 gene and a region located upstream of the GREM1 locus (upstream) may increase the risk of colorectal cancer (Jaeger et al., 2012; Yang et al., 2014b). The SERPINB2 gene encodes member 2 of the n / ccnn / zznz / E / YiAi serpine peptidase inhibitor, cyado B (ovalbumin), an inhibitor of extracellular urokinase-type plasminogen activator and tissue plasminogen activator (Schroder et al. al., 2014). SERPINB2 is expressed in different types of tumors. SERPINB2 expression is associated with favorable prognosis in breast and pancreatic tumors, but with poor prognosis in endometrial, ovarian, and colorectal cancer (Schroder et al., 2014). The SERPINB3 gene encodes the serpin peptidase inhibitor, cyado B (ovalbumin), member 3, a protease inhibitor (RefSeq, 2002). SERPINB3 is a Ras-responsive factor that plays an important role in Ras-associated cytokine production and oncogenesis ( Catanzaro et al., 2014 ). SERPINB3 expression is upregulated in hepatocellular carcinoma (Pontisso, 2014). SERPINB3 is associated with the development of ovarian cancer (Lim and Song, 2013). The SERPINB4 gene encodes the serpin peptidase inhibitor, cyado B (ovalbumin), member 4, a protease inhibitor (RefSeq, 2002). SERPINB4 is a Ras-responsive factor that plays an important role in Ras-associated cytokine production and oncogenesis ( Catanzaro et al., 2014 ). SERPINB4 expression is upregulated in hepatocellular carcinoma (Pontisso, 2014). The SERPINH1 gene encodes the serpin peptidase inhibitor, cyado H (heat shock protein 47), member 1, (collagen-binding protein 1), an inhibitor of serine proteinases. SERPINH1 acts as a specific molecular chaperone for collagen in the endoplasmic reticulum (RefSeq, 2002). SERPINH1 was shown to be overexpressed in many human cancers, such as gastric cancer, lung cancer, pancreatic duct adenocarcinoma, glioma, and ulcerative colitis-related carcinomas ( Zhao et al., 2014 ). The SEZ6L gene encodes seizure-related pseudohomolog (mouse) 6, a multidomain transmembrane protein involved in protein interaction and signal transduction (Nishioka et al., 2000). SEZ6L is n / ccnn / zznz / Ε / γΐΛΐ hypermethylated in gastric cancer (Kang et al., 2008). SEZ6L expression is upregulated in non-small cell and small cell lung cancer strains as well as in primary tumor samples compared to normal lung tissues (Gorlov et al., 2007). The SLC16A3 gene encodes solute transporter family 16 member 3, a proton-linked monocarboxylate transporter (RefSeq, 2002). It is known that most solid tumors depend on glycolysis for energy production. Accelerated glycolysis increases lactate production, which has been linked to a negative clinical outcome and a direct contribution to tumor growth and progression. SLC16A3 is one of the few monocarboxylate transporters that facilitates lactate export in cancer cells (Dhup et al., 2012; Draoui and Feron, 2011). SLC16A3 expression has been associated with a poor prognosis in patients with hepatocellular cancer and with increased cell proliferation, migration, and invasion in experiments with cell lines (Gao et al., 2014a). The functional involvement of SLC16A3 in oncogenesis has been demonstrated in a subgroup of pancreatic cancer (Baek et al., 2014). The MTCL1 gene encodes microtubule cross-linking factor 1. MTCL1 has been shown to mediate polarity-dependent microtubule remodeling and mediate epithelial cell-specific non-centrosomal microtubule reorganization through its cross-link forming activity (Sato et al., 2013). The SST gene encodes the preproprotein of the hormone somatostatin. Somatostatin is expressed throughout the body and inhibits the release of numerous secondary hormones. This hormone is an important regulator of the endocrine system through its interactions with pituitary somatotropin, thyrotropin, and most digestive tract hormones. Somatostatin also influences neurotransmission rates in the central nervous system and the proliferation of normal and oncogenic cells (RefSeq, 2002). SST analogs have been used successfully and are being investigated as a therapeutic approach in the treatment of gastroenteropancreatic neuroendocrine tumors (carcinoids), hepatocellular cancer, and breast cancer (Pivonello et al. , 2014; Culler, 2011; Appetecchia and Baldelli, 2010; Modlin et al., 2010; Watt et al., 2008). The THY1 gene is a candidate to be an oncosuppressor gene in nasopharyngeal carcinoma endowed with anti-invasive activity (Lung et al., 2010). The TSC22D4 gene encodes a protein that belongs to the TSC22 domain family of leucine zipper transcriptional regulators (RefSeq, 2002). Hepatic TSC22D4 levels appeared increased in cancer cachexia (Jones et al., 2013). The TUBA1A gene encodes tubulin, alpha 1a. TUBA1A expression is predominantly detected in morphologically differentiated neurological cells. Mutations of this gene cause lissencephaly type 3 (LIS3) - a neurological disorder characterized by microcephaly, mental retardation and early epilepsy, caused by defects in neuronal migration (RefSeq, 2002). Deregulation of the expression of TUBA1A and certain other genes, caused by chromosomal recombinations in oncogenic and radiation-transformed breast cell lines, could reflect early molecular events of breast carcinogenesis (Unger et al., 2010). With comparative proteomic analysis of serous epithelial ovarian carcinoma, TUBA1A was identified as a potential predictor of chemoresistance ( Kim et al., 2011 ). The TUBA1B gene encodes tubulin, alpha 1b (RefSeq, 2002). Differential expression of TLJBA1 B in combination with the expression of certain other genes was associated with prognosis in mantle cell lymphoma, prediction of recurrence in patients with stage II colorectal cancer, and differentiation between uveal melanomas. that ended up metastasizing and those that did not (Blenk et al., 2008; Agesen et al., 2012; Linge et al., 2012). The expression of TUBA1 B appeared upregulated in hepatocellular cancer tissues and in proliferating cells of the same type of cancer. Increased n / ccnn / zznz / E / YiAi TUBA1B expression was associated with short overall survival and resistance to paclitaxel in patients with hepatocellular cancer (Lu et al., 2013a). In ovarian cancer cells, reduced TUBA1B expression was associated with oxaliplatin resistance (Tummala et al., 2009). The TUBA1C gene encodes tubulin, alpha 1c (RefSeq, 2002). TUBA1C expression has been shown to be upregulated in elosteosarcoma and HCV-linked hepatocellular cancer, and could be a potential biomarker for the oncogenesis of osteosarcoma or differentiated HCV-linked hepatocellular cancer (Kuramitsu et al., 2011; L ¡ et al., 2010). The TUBA3C gene encodes tubulin, alpha 3c (RefSeq, 2002). The TUBA3D gene encodes tubulin, alpha 3d (RefSeq, 2002). The TUBA4A gene encodes tubulin, alpha 4a (RefSeq, 2002). Comparative proteomic analysis of esophageal squamous cell carcinoma (ESCC) revealed increased expression of TUBA4A ( Qi et al., 2005 ). The TUBA8 gene encodes tubulin, alpha 8. TUBA8 mutations are associated with polymicrogyria and optic nerve hypoplasia (RefSeq, 2002). In mouse liver, TUBA8 was induced after treatment with phenobarbital, a non-genotoxic carcinogen. In hepatocellular carcinoma cell lines, overexpression of TUBA8 has been shown to affect cell growth, proliferation and migration (Kamino et al., 2011). The UCN3 gene is a member of the sauvagin / corticotropin-releasing factor / urotensin I family. It is structurally related to the corticotropin-releasing factor (CRF) gene and the encoded product is an endogenous ligand of CRF type 2 receptors. . In the brain it could be responsible for the effects of stress on appetite (RefSeq, 2002). Ucn3 is produced by normal adrenal glands and by adrenal tumors (both adrenal corticosteroids and pheochromocytomas), and acts as an autocrine or paracrine regulator in these glands, both normal and affected by a tumor (Takahashi et al., 2006). . Urocortin 3 activates AMPK and AKT pathways and enhances glucose availability in rat skeletal muscle (Roustit et al., 2014). n / ccnn / zznz / Ε / γΐΛΐ The VCAN gene is a member of the aggrecan / versican family of proteoglycans. The encoded protein is a large chondroitin sulfate proteoglycan that is one of the major components of the extracellular matrix. This protein is involved in cell adhesion, proliferation and migration, as well as angiogenesis, and plays a central role in tissue morphogenesis and maintenance (RefSeq, 2002). VCAN expression was shown to be regulated in cancer-associated fibroblasts through TGF-beta type II receptor and SMAD signaling. Upregulated VCAN promoted ovarian cancer cell motility and invasion by activating the NF-kappaB signaling pathway and upregulating the expression of CD44, matrix metalloproteinase 9, and NF-kappaB-mediated motility receptor. hyaluronan (Yeung et al., 2013). A genetic signature of collagen remodeling including VCAN regulated by TGF-beta signaling is linked to metastasis and short survival in serous ovarian cancer ( Cheon et al., 2014 ). VCAN was shown to be markedly upregulated in colorectal cancer compared to paired samples of healthy colonic mucosa and tumor tissues from 53 patients (Pitule et al., 2013). The WNT16 gene, member 16 of the wingless MMTV integration point family, encodes a secreted signaling protein involved in oncogenesis and various developmental processes, including regulation of cell fate and regional specification (patterning) during embryogenesis (RefSeq, 2002). WNT16 expression was found to be upregulated in acute lymphoblastic leukemia (ALL) carrying the t(1;19) chromosomal translocation and plays an important role in leukemiagenesis (Casagrande et al., 2006; Mazieres et al., 2005). . A study using ALL cell lines and samples from ALL patients demonstrated that upregulation of WNT16 and a handful of other Wnt target genes was caused by methylation of Wnt inhibitors, which in turn was linked to a decrease in disease-free survival and 10-year overall survival (Roman-Gomez et al., 2007). n / ccnn / zznz / Ε / γΐΛΐ The WNT5A gene belongs to the WNT gene family consisting of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in various developmental processes, such as cell fate regulation and regional specification during embryogenesis. The WNT5A gene encodes a member of the WNT family that signals through both canonical and non-canonical WNT pathways. This protein is a ligand for the seven-pass transmembrane receptor frizzled-5 and orphan receptor tyrosine kinase 2. It fulfills an essential role in the regulation of developmental pathways during embryogenesis. It could also be involved in oncogenesis (RefSeq, 2002). WNT5A is overexpressed in colorectal cancer and has a concordance rate of 76% between the primary tumor and the metastatic focus (Lee et al., 2014). WNT5A is upregulated and a key regulator of epitheliomese nchymatic transition and metastasis in human gastric carcinoma, nasopharyngeal carcinoma, and pancreatic cancer cells (Kanzawa et al., 2013; Zhu et al., 2014; Bo et al., 2013). al., 2013). The stimulation of an immune response depends on the presence of antigens that are recognized as foreign by the host's immune system. The discovery of the existence of tumor-associated antigens has raised the possibility of using the host's immune system to intervene in the growth of tumors. Various mechanisms are currently being explored to take advantage of the humoral and cellular defenses of the immune system in cancer immunotherapy. Certain elements of the cellular immune response are capable of specifically recognizing and destroying tumor cells. The isolation of T lymphocytes among cells infiltrated in tumors or in the peripheral blood suggests that such cells play an important role in natural immune defenses against cancer. CD8-positive T cells in particular, which recognize major histocompatibility complex (MHC) class I molecules carrying peptides typically having 8 to 10 amino acid residues derived from proteins or n / ccnn / zznz / E products. Defective ribosomal / YiAi (DRIPS) located in the cytosol, play an important role in this response. Human MHC molecules are also called human leukocyte antigens (HLA). In this report all terms correspond to the definition indicated below, except in cases where otherwise indicated. The term “T cell response” defines the specific proliferation and activation of effector functions induced by a peptide in vitro or in vivo. In the case of MHC class I-restricted cytotoxic T lymphocytes, the effector functions may consist of the lysis of natural peptide-presenting target cells or those repeatedly sensitized with a peptide or a precursor thereof; peptide-induced secretion of cytokines, preferably gamma interferon, TNF-alpha or IL-2; peptide-induced secretion of effector molecules, preferably granzymes or perforins; or degranulation. The term "peptide" here designates a series of amino acid residues connected to each other typically by peptide bonds between the alpha-amino and carbonyl groups of adjacent amino acids. The peptides are preferably 9 amino acids in length, but may be only 8 amino acids in length, but also up to 10, 11, 12, 13, 14 or more, and in the case of MHC class II peptides (elongated variants of the peptides of the invention) can be up to 15, 16, 17, 18, 19 or 20 or more amino acids in length. Furthermore, the term "peptide" includes salts of a series of amino acid residues connected together typically by peptide bonds between the alpha-amino and carbonyl groups of adjacent amino acids. Preferably the salts are pharmaceutically acceptable salts of the peptides, such as, for example, chloride or acetate (trifluoroacetate) salts. It should be noted that the salts of the peptides according to the present invention differ substantially from the peptides in their in vivo state or states, since the peptides are not in salt form under such in vivo conditions. The term "peptide" also includes "oligopeptide." The term n / ccnn / zznz / E / YiAi “oligopeptide” here designates a series of amino acid residues connected to each other typically by peptide bonds between the alpha-amino and carbonyl groups of adjacent amino acids. The length of the oligopeptide is not crucial in the invention, as long as the appropriate epitope or epitopes are maintained. Oligopeptides usually have a length of less than about 30 amino acids and greater than approximately 15. The term "polypeptide" designates a series of amino acid residues connected to each other typically by peptide bonds between the alpha-amino and carbonyl groups of adjacent amino acids. The length of the polypeptide is not crucial in the invention, as long as the appropriate epitopes are maintained. In contrast to the terms "peptide" and "oligopeptide", the term "polypeptide" refers to molecules greater than about 30 amino acid residues in length. A peptide, oligopeptide, protein or polynucleotide encoding such a molecule is “immunogenic” (and therefore an “immunogen” in the present invention), if it is capable of inducing an immune response. In the case of the present invention, immunogenicity is more specifically defined as the ability to trigger a response by T lymphocytes. Therefore, an "immunogen" would be a molecule that is capable of inducing an immune response and, in In the case of the present invention, a molecule capable of inducing a T lymphocyte response. In another aspect, the immunogen can be the peptide, the complex of the peptide with MHC, the oligopeptide and / or the protein that is used to generate antibodies. or specific TCRs against him. A class I “epitope” of a T cell requires a short peptide that is linked to an MHC class I receptor, forming a ternary complex (MHC class I alpha chain, beta-2-microglobulin and peptide) that can be recognized by a T cell that carries a matching T cell receptor and that binds to the MHC / peptide complex with the appropriate affinity. Peptides that bind to MHC class I molecules are usually between 8 and 14 amino acids in length, and more commonly 9 amino acids. In humans, there are three different genetic loci that encode MHC class I molecules (human MHC molecules are also called human leukocyte antigens [HLA]): HLA-A, HLA- B and HLA-C. HLA-A*01, HLA-A*02, and HLA-B*07 are examples of different MHC class I alleles that can be expressed from these loci. Table 5: F expression frequencies of HLA-A*02 and HLA-A*24 and the most frequent HLA-DR serotypes. The frequencies are inferred from the Gf haplotype frequencies in the North American population adapted from Morí and collaborators (Morí et al., 1997) using the Hardy-Weinberg formula F = 1 -(1 -Gf)2. Combinations of A*02 or A*24 with certain HLA-DR alleles could be more or less abundant than expected from their isolated frequencies due to linkage disequilibrium. For more details see Chanock and collaborators (Chanock et al., 2004) The peptides of the invention, preferably when included in a vaccine of the invention as described herein will bind to A*02. A vaccine could also include peptides that bind to any MHC class II. Therefore, the vaccine of the invention can be used to treat cancer in patients who are A*02 positive, while non-selection for MHC class II allotypes is necessary due to the pan-unionist nature of those peptides. Combining A*02 peptides of the invention with peptides that bind to another allele, such as A*24, has the advantage that a greater percentage of any patient population can be treated than if it were only directed against a single MHC class I allele. While in most populations only less than 50% could be treated if only one of the alleles were chosen, a vaccine that includes HLA-A*24 and HLA-A*02 epitopes of The invention allows treating at least 60% of patients from any relevant population. Specifically, the percentages of patients positive for at least one of such alleles in various regions are as follows: USA 61%, Western Europe 62%, China 75%, South Korea 77%, Japan 86% (calculated from www.allelefrequencies.net). In a preferred embodiment, the term “nucleotide sequence” n / ccnn / zznz / Ε / γΐΛΐ refers to a heteropolymer of deoxyribonucleotides. The nucleotide sequence encoding a particular peptide, oligopeptide or polypeptide may be natural or synthetically constructed. Generally, DNA segments encoding the peptides, polypeptides and proteins of the present invention are assembled from cDNA fragments and short linker oligonucleotides, or from a series of oligonucleotides, in order to provide a synthetic gene capable of of being expressed in a recombinant transcriptional unit that comprises regulatory elements derived from a microbial or viral operon. As used herein the term “a nucleotide encoding a peptide” refers to a sequence of nucleotides that encodes the peptide and that includes artificial (man-synthesized) start and stop codons compatible with the biological system. in which the sequence is to be expressed by, for example, a dendritic cell or other cellular system useful for the production of TCR. Herein, reference to a nucleic acid sequence includes both single-stranded and double-stranded nucleic acid. Therefore, as far as DNA is concerned, for example, the specific sequence, unless the context indicates otherwise, refers to the single-stranded DNA of said sequence, to the double strand formed by said sequence with its complementary one (double-stranded DNA). and to the complementary strand of said sequence. The term "coding region" refers to the portion of a gene that, either naturally or normally, encodes the expression product of said gene in its natural genomic environment, for example, the region that encodes the product of expression in vivo. natural expression of the gene. The coding region may be derived from an unmutated ("normal"), mutated or altered gene, or may even come from a DNA sequence, or gene, synthesized entirely in the laboratory with methods well known to those skilled in DNA synthesis. . The term “expression product” defines the polypeptide or protein that is the natural product of gene translation and any nucleic acid sequence encoding n / ccnn / zznz / E / YiAi equivalents resulting from the degeneration of the genetic code and , therefore, that they code for the same amino acid or amino acids. The term “fragment,” when referring to a coding sequence, defines a portion of DNA that does not comprise the entire coding region, the expression product of which retains essentially the same biological activity or function as the expression product of the entire coding region. . The term “DNA segment” refers to a DNA polymer, in the form of a separate fragment or as a component of a larger DNA construct, that is derived from DNA isolated at least once in a substantially pure form, i.e. free of contaminating endogenous materials and in an amount or concentration that allows the identification, manipulation and recovery of the segment and its constituent nucleotide sequences by standard biochemical methods such as, for example, by means of a cloning vector. Such segments are supplied in the form of an open reading frame uninterrupted by internal untranslated sequences, or introns, which are typically present in eukaryotic genes. Untranslated DNA sequences may be present downstream from the open reading frame, where they do not interfere with the manipulation or expression of the coding regions. The term "primer" defines a short sequence of nucleic acids that can anneal to a DNA strand and that provides a free 3'-OH end at which a DNA polymerase can begin the synthesis of a deoxyribonucleotide chain. The term “promoter” defines a region of DNA involved in binding RNA polymerase to initiate transcription. The term “isolated” defines material that is removed from its original environment (for example, the natural environment, if it occurs naturally). For example, a natural polynucleotide or polypeptide present in a living animal is not isolated, but that same polynucleotide or polypeptide will be isolated if it is separated from some or all of the coexisting materials in the natural system. Such polynucleotides may form part of a vector and / or such polynucleotides or n / ccnn / zznz / E / YiAi polypeptides may form part of a composition, and continue to be isolated in said vector or composition since these are not part of their natural environment. The polynucleotides, and recombinant polypeptides or immunogens, described in accordance with the present invention may also be presented in "purified" form. The term “purified” does not imply absolute purity; rather, it is used as a relative definition and may include highly purified preparations or only partially purified preparations, as such terms are understood by those skilled in the art. For example, individual clones isolated from a cDNA library have been conventionally purified to electrophoretic homogeneity. Purification of the starting material or natural material up to at least one order of magnitude is expressly contemplated; preferably two or three orders of magnitude; and, more preferably, four or five orders of magnitude. Furthermore, the claimed polypeptide is expressly contemplated as having a purity of preferably 99.999%, or at least 99.99% or 99.9%; and, more conveniently, 99% by weight or greater. The expression products of the polypeptides and nucleic acids described in accordance with the present invention, as well as the expression vectors containing said nucleic acids and / or said polypeptides, can be used in "enriched form." As used herein, the term “enriched” means that the concentration of the material is at least about 2, 5, 10, 100 or 1000 times its natural concentration (for example), more advantageously 0.01% by weight. , and, preferably, about 0.1% at least, by weight. Enriched preparations of around 0.5%, 1%, 5%, 10% and 20% by weight are also contemplated. The sequences, constructs, vectors, clones and other materials comprising the present invention can be used, as appropriate, in their enriched or isolated form. The term "active fragment" defines a fragment, usually a peptide, polypeptide or nucleic acid sequence, that generates an immune response (i.e., possesses immunogenic activity) when administered - alone or, optionally, with a n / ccnn / zznz / E / YiAi suitable adjuvant or in a vector - to an animal, which may be a mammal such as, for example, a rabbit or a mouse, without excluding a human being; Said immune response takes the form of stimulation of a T lymphocyte response in the recipient animal, such as, for example, humans. Alternatively, the “active fragment” can also be used to induce a T cell response in vitro. As used herein, the terms "portion", "segment" and "fragment", when used in relation to polypeptides, refer to a continuous sequence of residues, such as amino acid residues, which sequence is a subset of a larger sequence. For example, if a polypeptide is subjected to treatment with any of the common endopeptidases, such as trypsin or chymotrypsin, the oligopeptides resulting from such treatment will represent portions, segments or fragments of the initial polypeptide. Used in relation to polynucleotides, these terms refer to the products produced by the treatment of said polynucleotides with any of the endonucleases. According to the present invention, the term "percent identity" or "percent identity", when referring to a sequence, means that a sequence is compared to a claimed or described sequence after aligning the sequence to be compared (the “compared sequence”) with the described or claimed sequence (the “reference sequence”). The percentage identity is then determined with the following formula: Percent identity = 100 [1 -(C / R)] where C is the number of differences between the reference sequence and the compared sequence along the alignment between the reference sequence and the compared sequence, where (I) each base or amino acid of the reference sequence that does not have an aligned base or amino acid in the compared sequence and (II) each gap in the reference sequence and (III) each aligned base or amino acid of the reference sequence that differs of an aligned base or amino acid of the n / ccnn / zznz / E / YiAi sequence compared, constitutes a difference; and (IV) the alignment has to start at position 1 of the aligned sequences; and R is the number of bases or amino acids in the reference sequence along the sequence alignment compared to any gap created in the reference sequence, also counted as one base or one amino acid. If there is an alignment between the compared sequence and the reference sequence for which the percent identity, calculated as specified above, is approximately equal to or greater than a specified minimum percent identity, then the compared sequence retains the specified minimum percent identity with the reference sequence, although there may be alignments in which the percentage identity calculated above is less than the specified percentage identity. As stated before, the present invention therefore relates to a peptide comprising a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 67 or a variant thereof that is 88% homologous to SEQ ID NO. 1 to SEQ ID NO. 67, or a variant thereof that induces the cross-reaction of T lymphocytes with said peptide. The peptides of the invention have the ability to bind to a molecule of the human major histocompatibility complex (MHC) class I or, in the case of elongated versions of said peptides, to a molecule of class II. In the present invention the term "homologous" refers to the degree of identity (see above Percent identity) between the sequences of two amino acid sequences, that is, peptide or polypeptide sequences. The aforementioned “homology” is determined by comparing the two sequences aligned under optimal conditions with the sequences to be compared. Sequence homology can be calculated by creating an alignment with the ClustalW algorithm, for example. Typically public databases provide software for sequence analysis, specifically Vector NTI, GENETYX or other tools. A person skilled in the art will be able to assess whether the T lymphocytes induced by a variant of the specific peptide will be able to react with the peptide itself (Appay et al., 2006; Colombetti et al. , 2006; Fong et al., 2001; Zaremba et al., 1997) By "variant" of the amino acid sequence the inventors mean that the side chains of, for example, one or two of the amino acid residues are altered (for example, by substituting them with the side chain of another natural amino acid residue or some other side chain) so that the peptide remains capable of binding to an HLA molecule in basically the same manner as a peptide consisting of the amino acid sequence indicated in SEQ ID NO. 1 to SEQ ID NO. 67. For example, a peptide can be modified to enhance or at least maintain the ability to interact and bind to the binding cleft of a suitable MHC molecule, such as HLA-A*02 or -DR, and in a manner that enhances or at least maintain the ability to bind to the TCR of activated T lymphocytes. These T cells can then react with and kill cells that express a polypeptide containing the natural amino acid sequence of the cognate peptide defined in aspects of the invention. As can be deduced from the literature and scientific databases (Rammensee et al., 1999; Godkin et al., 1997), certain positions of HLA-binding peptides are typically anchor residues that form a core sequence that fits into the HLA receptor binding motif, which is defined by the polar, electrophysical, hydrophobic, and spatial properties of the polypeptide chains that constitute the binding cleft. Thus, a person skilled in the art will be able to modify the amino acid sequences set forth in SEQ ID NO. 1 to SEQ ID NO. 67, maintaining the known anchor residues, and will be able to determine if such variants maintain the ability to bind to MHC class I or II molecules. Variants of the present invention retain the ability to bind to the TCRs of activated T lymphocytes, which can then react with and kill cells that express a polypeptide containing the natural amino acid sequence of the cognate peptide defined in aspects of the invention. . The original (unmodified) peptides described here can be modified by replacing one or more residues at different, possibly selective, sites within the peptide chain, if not otherwise specified. Preferably such substitutions would be located at the end of the amino acid chain. Such substitutions may be conservative in nature, such as if one amino acid is replaced by an amino acid of similar structure and characteristics, as in the case of a hydrophobic amino acid being replaced by another hydrophobic amino acid. Even more conservative would be the replacement of amino acids of the same or similar size and chemical nature, such as, for example, if a leucine is replaced by isoleucine. In various studies of sequence variations in naturally homologous protein families, certain amino acid substitutions are tolerated more frequently than others, and these often show a correlation with similarities in size, charge, polarity, and hydrophobicity between the original amino acid and its replacement. , this being the basis for the definition of “conservative substitutions”. Conservative substitutions are defined herein as exchanges within one of the following five groups: Group 1: small, non-polar or slightly polar aliphatic residues (Ala, Ser, Thr, Pro and Gly); Group 2: negatively charged polar residues and their amides (Asp, Asn, Glu and Gln); Group 3: positively charged polar residues (His, Arg and Lys); Group 4: large non-polar aliphatic residues (Met, Leu, He, Val and Cys); and Group 5: large aromatic residues (Phe, Tyr and Trp). Less conservative substitutions may involve the replacement of one amino acid with another with similar characteristics but differing in some way in size, as in the replacement of an isoleucine residue with alanine. Very little or no conservative replacements may involve the replacement of an acidic amino acid with another polar one, or even with one of a basic nature. These “radical” substitutions cannot be ruled out, however, as potentially ineffective, since the chemical effects are not entirely predictable and radical substitutions may well cause unexpected effects otherwise impossible to predict from chemical principles n / ccnn / simple zznz / E / YiAi. Naturally, such substitutions may involve structures other than the usual L amino acids. In this way, D amino acids could replace the L amino acids that are usually found in the antigenic peptides of the invention and, even so, be included in the description of the present document. In addition, other non-conventional amino acids (other than the natural amino acids that constitute proteins) may also be used for substitution purposes to produce immunogens and immunogenic polypeptides in accordance with the present invention. If substitutions at more than one position are found to result in a peptide with substantially equivalent or greater antigenic activity, as defined below, then combinations of such substitutions will be tested to determine whether the combined substitutions cause additive or synergistic effects on the peptide antigenicity. At most, up to 4 positions will be substituted simultaneously within the peptide. A peptide consisting essentially of the indicated amino acid sequence may have one or two non-anchor amino acids interchanged (see anchor motif below) without the ability to bind to a human major histocompatibility complex (MHC) molecule. class I or class II is substantially changed or negatively affected, compared to the unmodified peptide. In another embodiment, a peptide consisting essentially of the amino acid sequence set forth herein may have one or two amino acids changed to their conservative pairs (see below) without the ability to bind to a human major histocompatibility complex molecule ( MHC) class I or class II is substantially changed or negatively affected, compared to the unmodified peptide. Those amino acid residues that do not substantially contribute to interactions with the T cell receptor can be modified by replacing them with other amino acids whose incorporation does not substantially affect the reactivity of T cells and does not suppress binding to the relevant MHC. Thus, apart from the stated condition, the peptide of the invention may be any peptide (in which term the inventors include oligopeptides or polypeptides), including the amino acid sequences or a portion n / ccnn / zznz / E / YiAi or a variant thereof as indicated. Table 6: Variants and motifs of the peptides according to SEQ ID NO. 4, 29 and 30. Position 1 2 3 4 5 6 7 8 9 SEQ ID NO. 4 S V D V S P P K V Variants I L A L I L L L L A A I A L A A A M I ​​M L M M A T I T L T T A Q I Q L Q Q A Position 1 2 3 4 5 6 7 8 9 SEQ ID NO. 29 F L Q E Y L D A I Variants 1 L I V I I A M L M V M M A A L A V A A A V L V V V V A T L T V T T A Q L Q V Q Q A Position 1 2 3 4 5 6 7 8 9 SEQ ID NO. 30 V V D E G P T G V Variants L I A M L M I M M A L L n / ccnn / zznz / Ε / γΐΛΐ L I L L A A L A I A A A T L T I T T A Q L Q I Q Q A n / ccnn / zznz / Ε / γΐΛΐ Longer (elongated) peptides may also be suitable. It is also possible that MHC class I epitopes, although typically 8 to 11 amino acids in length, are generated by the processing of longer peptides or proteins that include the actual epitope. It is preferred that the residues flanking the epitope of interest be residues that do not substantially affect the proteolytic digestion necessary to expose the epitope during processing. The peptides of the invention can be extended up to four amino acids, that is, 1, 2, 3 or 4 amino acids can be added in any combination between 4:0 and 0:4. Below in Table 7 are combinations of the elongations according to the invention: Table 7: Combinations of the elongations of the peptides of the invention C-terminal N-terminal 4 0 3 0o 1 C-terminal N-terminal 2 0o1o2 1 0 O 1 O 2 0 3 0 0 o 1o2o3o4 N-terminal C-terminal 4 0 3 0 o 1 2 0o 1 02 1 0 o 1 o 2 o 3 0 0 o 1o2o3o4 n / ccnn / zznz / E / YiAi The amino acids for elongation / extension can be the peptides of the original protein sequence or any other amino acid. Elongation is intended to improve the stability or solubility of peptides. Thus, the epitopes of the present invention may be identical to natural tumor-specific or tumor-associated epitopes or may include epitopes that differ by at most four residues from the reference peptide, as long as they retain substantially the same antigenic activity. In an alternative embodiment, the peptide is elongated on one or both sides by more than 4 amino acids, preferably to a total length of up to 30 amino acids. This can result in peptides that bind to MHC class II. Binding to MHC class II can be analyzed with methods known in the art. Accordingly, the present invention also provides peptides and variants of MHC class I epitopes in which the peptide or variant has a total length of between 8 and 100, preferably between 8 and 30, and more preferably between 8 and 14, this is 8, 9, 10, 11, 12, 13, 14 amino acids, which in the case of class II binding peptides can also be 15, 16, 17, 18, 19, 20, 21 or 22 amino acids. Of course, the peptide or variant according to the present invention will have the ability to bind to a human major histocompatibility complex (MHC) class I or II molecule. Binding of a peptide or variant to an MHC complex can be analyzed with methods known in the art. Preferably, when peptide-specific T cells according to the present invention are tested against the substituted peptides, the peptide concentration at which the substituted peptides achieve a half-maximal increase in lysis over background is at most of about 1 mM, preferably at most about 1 μΜ, more preferably at most about 1 nM, and even more preferably at most about 100 pM, and more preferably at most about 10 pM. It is also preferred that the substituted peptide be recognized by the T lymphocytes of more than one individual, at least two, and more preferably three individuals. In a preferred embodiment of the invention the peptide consists or consists essentially of an amino acid sequence according to SEQ ID NO. 1 to SEQ ID NO. 67. "Consists essentially of" means that a peptide according to the present invention, in addition to the sequence according to any of SEQ ID NO. 1 to SEQ ID NO. 67 or a variant thereof, contains additional segments of amino acids located at the N- and / or C-terminus that are not necessarily part of the peptide that functions as an epitope for the epitope of MHC molecules. However, such segments may be important in facilitating the efficient introduction of the peptide according to the present invention into cells. In one embodiment of the present invention, the peptide is a part of a fusion protein comprising, for example, the N-terminal 80 amino acids of the invariant chain associated with the HLA-DR antigen (p33, hereinafter "l!" ) as shown in NCBI, GenBank accession number X00497. In other fusions, the peptides of the present invention can be fused with n / ccnn / zznz / E / YiAi an antibody as described herein, or with a functional part thereof, in particular by integrating it into the sequence of the antibody, to be specifically targeted by said antibody, or for example, with an antibody that is specific for dendritic cells as described herein. Additionally, the peptide or variant can be further modified to improve stability and / or binding to MHC molecules in order to trigger a more potent immune response. Methods for achieving such optimization of a peptide sequence are well known in the art and include, for example, the introduction of inverse peptide bonds or non-peptide bonds. In a reverse peptide bond the amino acid residues are not linked by peptide bonds (-CO-NH-) but the peptide bond is inverted. These retro-inverse peptidomimetics can be synthesized with methods known in the art, such as those described by Meziere and collaborators (1997) (Meziere et al., 1997), and which are incorporated herein by reference. This strategy involves the synthesis of pseudopeptides that contain changes in the main structure, but not in the orientation of the side chains. Meziere and colleagues (Meziere et al., 1997) demonstrate that these pseudopeptides are useful for MHC binding and T helper cell responses. Retroinverse peptides, which contain NH-CO bonds instead of CO-NH peptide bonds, are much more resistant to proteolysis. Non-peptide bonds are, for example: -CH2-NH, -CH2S-, CH2CH2-, -CH=CH-, -COCH2-, -CH(OH)CH2- and -CH2SO-, US Patent No. 4, 897, 445 provides a method for the solid phase synthesis of non-peptide bonds (-CH2-NH) in polypeptide chains that involves obtaining polypeptides with standard procedures and the synthesis of the non-peptide bond by the reaction of an aminoaldehyde and an amino acid in the presence of NaCNBH3. Peptides comprising the sequences described above can be synthesized with other chemical groups added at the amino and / or carboxy termini, in order to improve the stability, bioavailability and / or affinity of the peptides. peptides. For example, hydrophobic groups such as carbobenzoxyl, dansyl, or tbutyloxycarbonyl groups can be added to the amino termini of peptides. Similarly, an acetyl group or a 9fluorenylmethoxycarbonyl group can be placed at the amino termini of peptides. Also, for example, the hydrophobic t-butyloxycarbonyl group, or an amido group can be added at the carboxy termini of the peptides. Additionally, the peptides of the invention can be synthesized to alter their steric configuration. For example, the D-isomer of one or more of the amino acid residues of the peptide may be used instead of the usual L-isomer. And even more, at least one of the amino acid residues of the peptides of the invention can be replaced by one of the known non-natural amino acid residues. Alterations such as these may serve to increase the stability, bioavailability and / or binding capacity of the peptides of the invention. Similarly, a peptide or variant of the invention can be chemically modified by reaction with specific amino acids before or after synthesis of the peptide. Examples of such modifications are well known in the art and are summarized for example in R. Lundblad, Chemical Reagents for Protein Modification, 3rd edition, CRC Press, 2004 (Lundblad, 2004), which is incorporated herein by reference. Chemical modification of amino acids includes, but is not limited to, modification by acylation, amidination, pyridoxylation of lysine, reductive alkylation, trinitrobenzylation of amino groups with 2,4,6trinitrobenzenesulfonic acid (TNBS), transformation of carboxyl groups to amide groups, and oxidation of the sulfhydryl group with performic acid to convert cysteine ​​to cysteic acid, formation of mercurial derivatives, formation of mixed disulfides with other thiol compounds, reaction with maleimide, carboxymethylation with iodoacetic acid or iodoacetamide and carbamoylation with cyanate at alkaline pH, but not limited thereto . In this regard, those skilled in the art are referred to Chapter 15 of Current Protocols In Protein Science, Eds. Coligan et n / ccnn / zznz / Ε / γΐΛΐ al. (John Wiley and Sons NY 1995-2000) (Coligan et al., 1995), where you will find a more extensive methodology related to the chemical modification of proteins. In summary, the modification of for example arginyl residues of proteins is often based on the reaction of adjacent dicarbonyl compounds such as f e n i I g I i o xal, 2,3-butanedione and 1,2cyclohexanedione to form an adduct. Another example is the reaction of methylglyoxal with arginine residues. The cisterna can be modified without the simultaneous modification of other nucleophilic sites as occurs with lysine and histidine. Thus, a large number of reagents are available for modification of the tank. The websites of companies such as Sigma-Aldrich (http: / / www.sigma-aldrich.com) offer information on specific reagents. Selective reduction of protein disulfide bridges is also common. The heat treatment to which biopharmaceutical products are subjected sometimes generates and oxidizes disulfide bridges. Woodward's reagent K can be used to modify specific glutamic acid residues. N-(3(dimethylamino)propyl)-N'-ethylcarbomide can be used to form intramolecular cross-links between a lysine residue and a glutamic acid residue. For example, diethylpyrocarbonate is a reagent used for the modification of histidyl residues in proteins. Histidine can also be modified with 4-hydroxy-2-nonenal. The reaction of lysine residues and other α-amino groups is useful, for example, for the attachment of peptides to surfaces or for the formation of cross-links between proteins / peptides. Lysine is the attachment site for poIi(etiIen)gIicoI and the main modification site in protein glycosylation. Methionine residues of proteins can be modified, for example, with iodoacetamide, bromoethylamine and chloramine T. Tyrosyl residues can be modified with tetranitromethane and N-acetylimidazole. Cross-linking via dityrosine formation can be accomplished with hydrogen peroxide / copper ions. Recent studies on the modification of tryptophan have used N-bromosuccinimide, 2-hydroxy-5-nitrobenzylbromide or 3bromo-3-methyl-2-(2-nitrophenylmercapto). )-3H-índole (BPNS-skatole). Modification of therapeutic proteins and peptides with PEG is often associated with a prolongation of half-life in circulation, while cross-linking of proteins with glutaraldehyde, polyethylene glycol diacrylate and formaldehyde is used in the preparation of hydrogels. Chemical modification of allergens for immunotherapy purposes is often achieved by carbamylation with potassium cyanate. A peptide or variant that is modified or includes non-peptide bonds is a preferred embodiment of the invention. In general, peptides and variants (at least those containing peptide bonds between amino acid residues) can be synthesized, for example, using solid phase peptide synthesis by the Fmoc-polyamide method, as shown by Lukas et al. (Lukas et al. al., 1981) and the references shown therein. The provisional protection of the N-amino group is achieved with the 9fluorenylmethyloxycarbonyl (Fmoc) group. Repeated cleavage of this very basic pH-sensitive protecting group is carried out with 20% piperidine in Ν,Ν-dimethylformamide. The functional groups of the side chains could be protected if they were transformed into butyl ethers (in the case of serine, threonine and tyrosine), butyl esters (in the case of glutamic and aspartic acid), butyloxycarbonyl derivatives (in the case of lysine and histidine), tritylated derivatives (in that of cysteine) and 4-methoxy-2,3,6-trimethylbenzenesulfonyl derivatives (in that of arginine). When the C-terminal residues are glutamine or asparagine, the 4,4'-dimethoxybenzhydryl group is used to protect the amido functional groups of the side chain. The solid phase support is based on a polydimethyl-acrylamide polymer made up of the three monomers dimethylacrylamide (structural monomer), bisacryloylethylenediamine (cross-linker) and acryloylsarcosine methyl ester (functionalizer). The cleavage agent that holds the peptide attached to the resin is a derivative of 4-hydroxymethylphenoxyacetic acid, sensitive to acidic pH. All amino acid derivatives are added as preformed symmetric anhydride derivatives except asparagine and n / ccnn / zznz / Ε / γΐΛΐ glutamine, which are added using a reverse coupling procedure with N,N-di¡cyclohex¡l- carbomide / 1-hydroxybenzotriazole. All coupling and deprotection reactions are monitored with ninhydrin, trinitrobenzenesulfonic acid, or isotine assay procedures. Once the synthesis is completed, the peptides are separated from the resin support and at the same time the protecting groups of the side chains are removed by treatment with 95% trifluoroacetic acid with a mixture of 50% scavengers. The sea avengers normally used are etandhiol, phenol, anisole and water, depending on the exact choice of the constituent amino acids of the peptide being synthesized. Peptide synthesis is also possible by combining solid phase and solution phase methodologies (see, for example, (Bruckdorfer et al., 2004) and the references cited therein). The trifluoroacetic acid is removed by evaporation in vacuo and trituration is carried out with diethyl ether to obtain the crude peptide. All scavengers are eliminated with a simple extraction procedure that, with the I i o f i I i z a t i o n of the aqueous phase, provides the crude peptide free of them. Reagents for peptide synthesis are generally available for example from CalbiochemNovabiochem (Nottingham, UK). Purification can be carried out by any technique or combination of techniques such as recrystallization, size exclusion chromatography, ion exchange chromatography, hydrophobic interaction chromatography, and (usually) reversed phase high performance liquid chromatography using e.g. acetonitrile / water gradient separation. Analysis of the peptides can be carried out using thin layer chromatography, electrophoresis, in particular capillary electrophoresis, solid phase extraction (CSPE), reversed phase high performance liquid chromatography, analysis of amino acids after acid hydrolysis and analysis with mass spectrometry. by fast atom bombardment (FAB), as well as analysis with MALDI and ESI-Q-TOF mass spectrometry. To select the overpresented peptides, an n / ccnn / zznz / E / YiAi presentation profile is calculated that shows the median presentation of the sample, as well as the variation of the duplicates. The profile juxtaposes samples of the tumor entity of interest with normal reference tissue samples. Each of those profiles can then be consolidated into an overpresentation score by calculating the p-value of a linear mixed-effects model (Pinheiro et al., 2015) adjusting for multiple analysis with the False Discovery Rate ( Benjamini and Hochberg, 1995). For the identification and relative quantification of HLA ligands by mass spectrometry, HLA molecules were purified from cryogenic tissue samples and HLA-associated peptides were isolated. Isolated peptides were separated and their sequences identified by online nano-electrospray ionization (nanoESI) liquid chromatography-mass spectrometry. The resulting peptide sequences were verified by comparing the fragmentation pattern of natural TUMAPs recorded from pancreatic cancer samples (N = 18 A*02-positive samples) with the fragmentation patterns of synthetic reference peptides of identical sequence. Since the peptides were directly identified as ligands for HLA molecules from primary tumors, these results provide direct evidence for the natural processing and presentation of the identified peptides in primary tumor tissue obtained from 18 pancreatic cancer patients. The patented XPRESIDENT® v2 drug discovery platform. 1 (see for example US 2013-0096016, which is incorporated in its entirety herein) allows the identification and selection of peptide vaccine candidates that are overrepresented based on the relative quantification of the levels of HLA-restricted peptides in cancer tissues regarding various normal tissues and organs. This was achieved by developing label-free differential quantification with acquired LC-MS data processed with a proprietary data analysis platform that combines algorithms for sequence identification, spectral clustering, ion counting, retention time alignment , charge state deconvolution and n / ccnn / zznz / Ε / γΐΛΐ normalization. Presentation levels were calculated including error estimates for each peptide and each sample. Peptides presented exclusively in tumor tissue and peptides overpresented in tumor tissue with respect to non-cancerous tissues and organs were identified. HLA-peptide complexes present in pancreatic cancer tissue samples were purified and HLA-associated peptides were isolated and then analyzed with LC-MS (see examples). All TUMAPs contained in the present application were identified with this strategy in primary pancreatic cancer samples to confirm their presentation in primary pancreatic cancer. TUMAPs identified in multiple normal and pancreatic cancer tumor tissues were quantified with ion counting from label-free LC-MS data. The method assumes that the LC-MS signal areas of a peptide are correlated with its abundance in the sample. All quantitative signals produced by each peptide in several LC-MS experiments were normalized with measures of central tendency, averaged per sample, and combined into a bar plot, called the display profile. The presentation profile combines various analysis methods such as protein database searching, spectral clustering, charge (discharge) state deconvolution, and retention time alignment and normalization. The present invention provides peptides that are useful for the treatment of cancers / tumors, preferably pancreatic cancer, that overrepresent or exclusively present the peptides of the invention. Using mass spectrometry techniques, the natural presentation by HLA molecules of these peptides has been demonstrated in human samples of primary pancreatic cancer. It has been shown that the parent gene(s) / protein(s) (also called "whole proteins" or "underlying proteins") from which the peptides are derived are markedly overexpressed in cancerous tissues with respect to normal tissues - in the present invention “Normal tissues” means that they are healthy pancreatic cells or cells from other normal tissues – which demonstrates the high degree of relationship of the originating genes with the tumor (see example 2). Furthermore, the peptides themselves are strongly overpresented in the tumor tissue - in the present invention "tumor tissue" is understood as a sample taken from a patient suffering from pancreatic cancer, but not from normal tissues (see Example 1). HLA-binding peptides can be recognized by the immune system, specifically by T lymphocytes. T lymphocytes destroy cells that present the HLA / recognized peptide complex, for example, pancreatic tumor cells that present the derived peptides. The peptides of the present invention have demonstrated their ability to stimulate T lymphocyte responses and / or are overrepresented and, therefore, can be used for the production of antibodies and / or TCRs, specifically soluble TCRs, in accordance with the present invention (see Example 3 and Example 4). Likewise, when the peptides are forming a complex with the corresponding MHC, they can also be used for the production of antibodies and / or TCRs, specifically soluble TCRs, in accordance with the present invention. The relevant methods are known to those skilled in the art and can also be found in the relevant literature. Thus, the peptides of the present invention are useful for generating an immune response in a patient with which to destroy tumor cells. The immune response can be induced in the patient with the direct administration of the described peptides or of suitable precursor substances (for example, elongated peptides, proteins or nucleic acids encoding said peptides), ideally in combination with an agent that enhances immunogenicity ( an adjuvant). The immune response generated by such therapeutic vaccination is expected to be highly specific against tumor cells because normal tissues do not contain the target peptides of the present invention in a comparable number of copies, which avoids the risk of harmful autoimmune reactions against the cells. normal of the patient. n / ccnn / zznz / E / YiAi A “pharmaceutical composition” is a composition suitable for administration to a human being in a medical context. Preferably, said pharmaceutical composition is sterile and is manufactured in accordance with Good Manufacturing Practice (GMP) guidelines. The pharmaceutical compositions may comprise the peptides in free form or in the form of a pharmaceutically acceptable salt (see also above). As used herein, "pharmaceutically acceptable salt" refers to a derivative of the described peptides in which the peptide is modified to obtain acidic or basic salts of the agent. For example, acid salts are prepared from the free base (usually the neutral form of the drug has a neutral -NH2 group) by reacting it with a suitable acid. Suitable acids for the preparation of acid salts include both organic acids, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, acid citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, ptoluenesulfonic acid, salicylic acid and the like, such as inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like. Conversely, the preparation of basic salts from acidic groups that may be present in a peptide are prepared using a pharmaceutically acceptable base such as sodium hydroxide, potassium hydroxide, ammonium hydroxide, calcium hydroxide, trimethylamine or the like. In an especially preferred embodiment, the pharmaceutical compositions comprise the peptides in the form of salts of acetic acid (acetates), trifluoroacetates or hydrochloric acid (chlorides). Preferably, the medicament of the present invention is an immunotherapeutic agent such as a vaccine. The vaccine can be administered directly to the patient, in the affected organ or systemically i. gave. m, s. c., i. p. and i. v., or applied ex vivo to cells derived from the patient or a human cell line that is then administered to the patient, or used in vitro to select a subpopulation of immune cells derived from the patient that are then n / ccnn / zznz / E / YiAi They administer it again. If the nucleic acid is administered to cells in vitro, it may be useful for these cells to be transfected to simultaneously express immunostimulatory cytokines, such as interleukin-2. The peptide may be substantially pure, or combined with an immunostimulatory adjuvant (see below) or used in combination with immunostimulatory cytokines, or administered by another suitable delivery system, such as liposomes. The peptide can also be conjugated to a suitable carrier such as keyhole limpet hemocyanin (KLH) or mannan (see WO 95 / 18145 and (Longenecker et al., 1993)). The peptide may also be labeled, or be a fusion protein, or be a hybrid molecule. Peptides whose sequence is offered in the present invention are expected to stimulate CD4 or CD8 T lymphocytes. However, the stimulation of CD8 T cells is more efficient if they have the help of CD4 T helper cells. Thus, in the case of MHC class I epitopes that stimulate CD8 T cells the fusion partner or sections of a suitable hybrid molecule provide epitopes that stimulate CD4-positive T cells. CD4 and CD8 stimulatory epitopes are well known in the art and include those identified in the present invention. In one aspect, the vaccine comprises at least one peptide having the amino acid sequence set forth in SEQ ID NO. 1 to SEQ ID NO. 67 and at least one additional peptide, preferably two to 50, more preferably two to 25, even more preferably two to 20 and even more preferably two, three, four, five, six, seven, eight, nine, ten, eleven, twelve , thirteen, fourteen, fifteen, sixteen, seventeen or eighteen peptides. Peptides can be derived from one or more specific TAAs and can bind to MHC class I molecules. Another aspect of the invention provides a nucleic acid (for example a polynucleotide) that encodes a peptide or peptide variant of the invention. The polynucleotide may be, for example, DNA, cDNA, PNA, RNA or combinations thereof, single-stranded and / or double-stranded, or native or stabilized forms of polynucleotides, such as, for example, polynucleotides with a phosphorothioate backbone and which n / ccnn / zznz / Ε / γΐΛΐ can contain introns as long as it encodes the peptide. Of course, only peptides containing natural amino acid residues linked by natural peptide bonds can be encoded by a polynucleotide. Still another aspect of the invention provides an expression vector capable of expressing a polypeptide according to the invention. Various methods have been developed to link polynucleotides, especially DNA, to vectors, for example through complementary cohesive ends. For example, complementary homopolymer extensions can be added to the DNA segment to insert it into the DNA vector. The vector and the DNA segment are then joined by hydrogen bonding between complementary homopolymeric tails to form recombinant DNA molecules. Another alternative method to join the DNA segment to the vectors is synthetic linkers that contain one or more restriction sites. Commercial synthetic linkers containing various targets for restriction endonucleases are available from various suppliers such as International Biotechnologies Inc. New Haven, CT, USA. A desirable method for modifying the DNA encoding the polypeptide of the invention employs the polymerase chain reaction as set forth by Saiki RK et al. (Saiki et al., 1988). This method can be used to introduce the DNA into a suitable vector, for example by designing appropriate restriction sites, or it can be used to modify the DNA in other useful ways known in the art. If viral vectors are chosen, poxviral or adenoviral vectors are preferable. The DNA (or RNA in the case of retroviral vectors) can be expressed in a suitable host to produce a polypeptide comprising the peptide or variant of the invention. Thus, the DNA encoding the peptide or variant of the invention can be used according to known techniques, suitably modified following the teachings contained herein to construct an expression vector that is used to transform a n / ccnn / zznz / E / YiAi host cell in order to express and produce the polypeptide of the invention. Such techniques include those disclosed in United States Patent Nos. 4,440,859; 4,530,901; 4,582,800; 4,677,063; 4,678,751; 4,704,362; 4,710,463; 4,757,006; 4,766,075 and 4.81 0.648. The DNA (or RNA in the case of retroviral vectors) encoding the polypeptide constituting the compound of the invention can be linked to a wide variety of different DNA sequences to introduce it into a suitable host. The accompanying DNA will depend on the nature of the host, the way the DNA is introduced inside and whether it is intended to be integrated or maintained as an episome. In general, DNA is inserted into an expression vector, such as a plasmid, in the appropriate orientation and correct reading frame to ensure expression. If necessary, the DNA can be linked to control nucleotide sequences that regulate transcription or translation and that are recognized by the desired host, although in general such controls are usually already included in the expression vector itself. The vector is then introduced into the host using standard techniques. In general, the vector is not able to transform all the hosts, which will make it necessary to select the host cells that have been transformed. A selection technique consists of incorporating into the expression vector a DNA sequence with the necessary control elements that encodes a selectable trait in the transformed cell, such as antibiotic resistance. Another alternative is to incorporate the gene for that selectable trait into another vector with which the host cell is cotransformed. Host cells that have been transformed with the recombinant DNA of the invention will be cultured for sufficient time and under appropriate conditions known to those skilled in the art in view of the teachings described herein so that the polypeptide can be expressed and , finally, be recovered. There are many known expression systems, such as n / ccnn / zznz / E / YiAi bacteria (E. coli, Bacillus subtilis, etc.), yeasts (Saccharomyces cerevisiae, etc.), filamentous fungi (Aspergillus genus, etc.), plant, animal or insect cells. Preferably the system will consist of mammalian cells, such as the CHO cells available from the ATCC Cell Biology Collection. A typical constitutive expression plasmid vector for mammalian cells comprises the CMV or SV40 promoter with a suitable poly-A tail and a resistance marker such as neomycin. An example is pSVL offered by Pharmacia, Piscataway, NJ, USA. An example of an inducible mammalian expression vector is pMSG, also supplied by Pharmacia. Other yeast plasmid vectors are pRS403-406 and pRS413-416, generally provided by Stratagene Cloning Systems, La Jolla, CA 92037, USA. Plasmids pRS403, pRS404, pRS405 and pRS406 are yeast integrative plasmids (Ylp) that incorporate the yeast selectable markers HIS3, TRP1, LEU2 and URA3. Plasmids pRS413-416 are yeast centromeric plasmids (Ycp). Vectors provided with the CMV promoter (e.g. from Sigma-Aldrich) provide transient or stable expression, expression in the cytoplasm or secretion, and labeling of the N-terminal or C-terminal ends in various combinations of FLAG, 3xFLAG, c-myc or MAT. These fusion proteins allow detection, purification and analysis of the recombinant protein. Double-label fusions add flexibility to detection. The potent promoter regulatory region of human cytomegalovirus (CMV) offers very high constitutive expression levels of the protein, up to 1 mg / L in COS cells. In less potent cell lines protein levels are usually around ~0.1 mg / l. The presence of the SV40 origin of replication results in elevated levels of DNA replication in COS cells that tolerate SV40 replication. CMV vectors, for example, may contain the pMB1 origin (derived from pBR322) for replication in bacterial cells, the b-lactamase gene for selection for resistance to ampicillin, hGH polyA, and the f1 origin. Vectors containing the preprotrypsin (PPT) leader sequence can channel the n / ccnn / zznz / E / YiAi secretion of FLAG fusion proteins into the culture medium, where they can be purified by anti-FLAG antibodies, resins and plates. Other vectors and expression systems suitable for use with a variety of host cells are known in the art. In another embodiment two or more peptides or peptide variants of the invention are encoded and expressed in successive order (similar to “bead necklace” constructs). In doing so, peptides or peptide variants can be linked or fused together via linker amino acid segments, such as LLLLLL, or can be linked without any additional peptides between them. These constructs can also be used for cancer therapy, and could induce immune responses involving both MHC I and MHC II. The present invention also relates to a host cell transformed with a polynucleotide vector of the present invention. The host cell can be prokaryotic or eukaryotic. Bacterial cells may be the most suitable prokaryotic host cells under certain circumstances; These are typically E. coli strains, such as strains DH5 available from Bethesda Research Laboratories Inc., Bethesda, MD, USA, and RR1 available from the American Type Culture Collection (ATCC), Rockville, MD, USA. USA (ATCC no. 31343). Preferred eukaryotic host cells are yeast, insect and mammalian cells, preferably vertebrate cells such as mouse, rat, monkey or human colon and fibroblast cell lines. Yeast host cells include YPH499, YPH500 and YPH501, which generally can be obtained from Stratagene Cloning Systems, La Jolla, CA 92037, USA. Preferred mammalian host cells include the available Chinese hamster ovary (CHO) cells. from ATCC as CCL61, NIH / 3T3 Swiss mouse embryonic cells available from ATCC as CRL 1658, monkey kidney COS-1 cells available from ATCC as CRL 1650 and 293 cells which are human embryonic kidney cells. Preferred insect cells are Sf9 cells which can be transfected with baculoviral expression vectors. A general review regarding the choice of the most suitable host cells can be found, for example, in the manual by Paulina Balbás and Argelia Lorence “Methods in Molecular Biology Recombinant Gene Expression, Reviews and Protocols”, Part One, Second Edition, ISBN 978-1-58829-262-9, and other bibliography known to those skilled in the art. Transformation of suitable host cells with the DNA construct of the present invention is accomplished by known methods that typically depend on the type of vector used. Regarding the transformation of prokaryotic host cells, see for example Cohén and collaborators (Cohén et al., 1972) and (Green and Sambrook, 2012). The transformation of yeast cells described in Sherman and collaborators (Sherman et al., 1986). The Beggs method (Beggs, 1978) is also useful. Reagents suitable for transfecting vertebrate cells, for example calcium phosphate and DEAE-dextran or liposome formulations, can be purchased from Stratagene Cloning Systems, or Life Technologies Inc., Gaithersburg, MD 20877. , USA Electroporation is also useful for the transformation and / or transfection of cells and its application in the transformation of yeast, bacteria, insect and vertebrate cells is well known. Successfully transformed cells, that is, those containing a DNA construct of the present invention, can be identified with well-known techniques such as PCR. Another alternative is to detect the presence of the protein in the supernatant using antibodies. It will be appreciated that certain host cells of the invention are useful for the preparation of peptides of the invention, for example bacterial, yeast and insect cells. However, other host cells may be useful for certain therapeutic methods. For example, antigen presenting cells such as dendritic cells can be used to express the peptides of the invention such that they can be loaded onto the appropriate MHC molecules. Thus, the present invention provides a host cell comprising a nucleic acid or an expression vector according to the invention. n / ccnn / zznz / E / YiAi In a preferred embodiment the host cell is an antigen-presenting cell, in particular a dendritic cell or antigen-presenting cell. APCs loaded with a recombinant fusion protein containing prosthetic acid phosphatase (PAP) were approved by the US Food and Drug Administration (FDA) on April 29, 2010 to treat asymptomatic metastatic hormone-refractory prostate cancer. or minimally symptomatic (Sipuleucel-T) (Rini et al., 2006; Small et al., 2006). Another aspect of the invention provides a method for the production of a peptide or its variant, said method comprising the cultivation of a host cell and the isolation of the peptide from said cell or its culture medium. In another embodiment, the peptide, nucleic acid or expression vector of the invention is used in medicine. For example, the peptide or its variant can be prepared for injection intravenously (i.v.), subcutaneous (s.c.), intradermal (i.d.), intraperitoneal (i.p.) or intramuscular (i.m.). Preferred methods for peptide injection include s.c., i.d., i.p., i.m. and i.v. Preferred methods for DNA injection include i.d., i.m., s.c., i.p. and i.v. Depending on the peptide or DNA in question, doses of, for example, between 50 pg and 1.5 mg, preferably 125 pg to 500 pg of peptide or DNA, can be administered. Doses in these ranges have been used successfully in several trials (Walter et al., 2012). The polynucleotide used for active vaccination may be substantially pure, or contained in a vector or a suitable delivery system. The nucleic acid may be DNA, cDNA, PNA, RNA or a combination thereof. The methods for designing and introducing that nucleic acid are well known to those skilled in the art. A general perspective can be consulted, for example, in Teufel and collaborators (Teufel et al., 2005). Polynucleotide vaccines are easy to prepare, but the mechanism by which such vectors induce the immune response is not exactly known. Suitable vectors and delivery systems include those of viral DNA and / or RNA, such as systems based on adenovirus, vaccinia virus, retrovirus, herpesvirus, adeno-associated virus or hybrids that contain n / ccnn / zznz / E / YiAi elements. various viruses. Non-viral delivery systems include cationic lipids and cationic polymers which are well known as techniques for DNA introduction. Physical introduction methods, such as the “gene gun”, can also be used. The peptide or peptides encoded by the nucleic acid may be a fusion protein, for example with a T cell stimulating epitope for the respective opposite CDR as indicated above. The medicament of the invention may also include one or more adjuvants. Adjuvants are substances that non-specifically enhance or stimulate the immune response (for example, immune responses mediated by CD8-positive T lymphocytes and T helper lymphocytes (TH) against an antigen, so they could be considered useful in the drug of the Suitable adjuvants include, but are not limited to: 1018 ISS, aluminum salts, AMPLIVAX®, AS15, BCG, CP-870, 893, CpG7909, CyaA, dSLIM, flagellin or flagellin-derived TLR5 ligands, FLT3, GM-CSF, IC30, IC31, Imiquimod (ALDARA®), resiquimod, ImuFact IMP321, interleukins such as IL-2, IL-13, IL-21, alpha or beta interferon or pegylated derivatives thereof, IS Patch, ISS , ISCOMATRIX, ISCOMs, Juvlmmune®, LipoVac, MALP2, MF59, monophosphoryl lipid A, Montanide IMS 1312, Montanide ISA 206, Montanide ISA 50V, Montanide ISA-51, water-in-oil and oil-in-water emulsions, OK-432, OM-174, OM-1 97-MP-EC, ONTAK, OspA, PepTel® vector system, dextran and poly(lactide co-glycoIide) [PLG] microparticles, talactoferrin SRL172, virosomes and other virus-like particles, YF -17D, VEGF trap, R848, beta-glucan, Pam3Cys, QS21 stimulus from Aquila, which is derived from saponin, extracts of mycobacteria and synthetic mimetics of the bacterial wall, and other patented adjuvants such as Detox from Ribi, Quil or Superfos. Adjuvants such as Freund's adjuvant or GM-CSF are preferred. Several immunological adjuvants (e.g., MF59) specific for dendritic cells, as well as their preparation, have been described previously (Allison and Krummel, 1995). Cytokines can also be used. Several cytokines have been attributed a direct influence on the migration of dendritic cells towards lymphoid tissues (for example, TNF-), as part of a process that accelerates their maturation until they become on antigen-presenting cells of T lymphocytes (e.g., GM-CSF, IL-1 and IL-4) (U.S. Patent No. 5,849, 589, incorporated herein in its entirety by reference) and in which they act as immunoadjuvants (for example, IL-12, IL-15, IL-23, IL-7, IFN-alpha, IFN-beta) (Gabrilovich et al., 1996). Immunostimulatory CpG oligonucleotides have also been reported to enhance the effects of adjuvants in vaccines. Without being limited to theory, CpG oligonucleotides act by activating the innate (non-adaptive) immune system through Toll-like receptors (TLR), primarily TLR9. TLR9 activation triggered by CpGs enhances antigen-specific humoral and cellular responses against a wide range of antigens, including peptide or protein antigens, live or killed viruses, dendritic cell vaccines, autologous cell vaccines, and polysaccharide conjugates, both in prophylactic and therapeutic vaccines. More importantly, they enhance the maturation and differentiation of dendritic cells, resulting in greater activation of TH1 cells and more potent generation of cytotoxic T lymphocytes (CTL), even without the help of CD4 T cells. The tendency towards the TH1 response caused by TLR9 stimulation is maintained even in the presence of vaccine adjuvants such as aluminum or incomplete Freund's adjuvant (IFA) that normally promote a bias towards the TH2 response. CpG oligonucleotides show even greater adjuvant activity when formulated or co-administered with other adjuvants or in formulations such as microparticles, nanoparticles, lipid emulsions or similar formulations, which are especially necessary to induce a potent response when the antigen is relatively weak. They also accelerate the immune response and allow antigen doses to be reduced by approximately two orders of magnitude, and antibody responses comparable to those achieved with the full n / ccnn / zznz / E / YiAi dose of CpG-free vaccine have been obtained in some experiments. (Krieg, 2006). United States Patent no. 6,406,705 B1 describes the combined use of CpG oligonucleotides, non-nucleic acid adjuvants and an antigen to induce an antigen-specific immune response. A preferred component of the pharmaceutical composition of the present invention is a TLR9 CpG antagonist known as dSLIM (double hairpin immunomodulator), manufactured by Mologen (Berlin, Germany). Other molecules that bind to TLRs such as RNAs that bind TLR 7, TLR 8 and / or TLR 9 can also be used. Examples of useful adjuvants also include chemically modified CpG (e.g., CpR, Idera), dsRNA analogs such as poly(l:C), and derivatives thereof (e.g., AmpliGen®, Hiltonol®, poly-(ICLC ), poly(IC-R), poly(l:C12U), non-CpG bacterial RNA or DNA, as well as antibodies and immunoactive small molecules such as cyclophosphamide, sunitinib, Bevacizumab®, celebrex, NCX-4016, sildenafil, tadalafil, vardenafil, sorafenib, temozolomide, temsirolimus, XL-999, CP-547632, pazopanib, VEGF Trap, ZD2171, AZD2171, anti-CTLA4, other antibodies that recognize key structures of the immune system (for example, anti-CD40, anti-TGF-beta, anti-TNF-alpha receptor) and SC58175, which can act therapeutically and / or as adjuvants. The amounts and concentrations of adjuvants and additives useful in the context of the present invention can be easily determined by those skilled in the art without too much experimentation. Preferred adjuvants are anti-CD40, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, CpG oligonucleotides and derivatives, poly-(l:C) and derivatives, RNA, sildenafil, and particulate formulations with PLG or virosomes. In a preferred embodiment of the pharmaceutical composition according to the invention the adjuvant is selected from the group consisting of colony-stimulating factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim), cyclophosphamide, imiquimod, resimiquimod and interferonalpha. n / ccnn / zznz / Ε / γΐΛΐ In a preferred embodiment of the pharmaceutical composition according to the invention, the adjuvant is selected from the group consisting of colony-stimulating factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim), cyclophosphamide, imiquimod. and resiquimod. In another preferred embodiment of the pharmaceutical composition according to the invention, the adjuvant is cyclophosphamide, imiquimod or resiquimod. The most preferred adjuvants are: Montanide IMS 1312, Montanide ISA 206, Montanide ISA 50V, Montanide ISA-51, poly-ICLC (Hiltonol®) and anti-CD40 mAb or combinations of the above. This composition is intended for parenteral administration, such as subcutaneously, intradermally or intramuscularly, or for oral administration. To do this, the peptides and optionally other molecules are dissolved or suspended in a pharmaceutically acceptable vehicle, preferably aqueous. In addition, the composition may contain excipients, such as buffers, binders, disintegrants, diluents, flavors, lubricants, etc. Peptides can also be administered together with immunostimulatory substances, such as cytokines. A wide list of excipients can be used in such a composition, such as those taken from A. Kibbe, Handbook of Pharmaceutical Excipients, (Kibbe, 2000). The composition can be used for the prevention, prophylaxis and / or treatment of adenomatous or cancerous diseases. Preferred formulations can be found in EP21 12253, for example. It is important to keep in mind that the immune response triggered by the vaccine according to the invention attacks cancer at different cellular stages and at different stages of development. In addition, different signaling pathways related to cancer are attacked. This represents an advantage over vaccines that are only directed against one or a few targets, which can allow the tumor to easily adapt to the attack (tumor evasion). Furthermore, not all tumors express the same pattern of antigens, so the combination of several tumor-associated peptides ensures that the tumor in question contains at least some of the targets. The composition has been designed such that n / ccnn / zznz / E / YiAi is expected to express several of the antigens and encompass several independent pathways required for tumor growth and maintenance. Thus, the vaccine can easily be used in off-the-shelf form for a broader patient population. This means that no further evaluation of biomarkers of antigen expression other than HLA typing will be necessary to select patients who will end up being treated with the vaccine, but it is still ensured that the stimulated immune response will attack simultaneously. to several targets, which is important for efficacy (Banchereau et al., 2001; Walter et al., 2012). As used herein, the term “carrier” refers to a molecule that specifically binds to a (e.g., antigenic) determinant. In one embodiment, a support is capable of directing the entity to which it has been attached (for example, a (second) antigen-bound portion) to a target site, for example to a specific type of tumor cell or tumor stroma carrier. of the antigenic determinant (for example, the complex of a peptide according to the present application). In another embodiment, a support is capable of activating signaling through its target antigen, for example a T cell receptor complex antigen. The supports include, among others, antibodies and fragments thereof, the antigen binding domains of a antibody, comprising a variable region of the antibody heavy chain and another variable region of the antibody light chain, binding proteins comprising at least one ankyrin repeat motif and molecules with a single antigen binding domain (SDAB), aptamers, TCR (soluble) and cells (modified) such as allogeneic or autologous T lymphocytes. To evaluate whether a molecule is a support that binds to a target, binding assays can be performed. “Specific” binding means that the support binds to the peptide-MHC complex of interest better than to other natural peptide-MHC complexes, to the extent that a support provided with an active molecule that is capable of killing a cell carrying the specific target cannot kill another cell that lacks that specific n / ccnn / zznz / E / YiAi target even if it presents another or other peptide-MHC complexes. Binding to other peptide-MHC complexes is irrelevant if the peptide in the cross-reactive peptide-MHC complex is not natural, i.e., not derived from the human HLA-peptidome. Tests to evaluate the destruction of target cells are well known in the art. They should be performed with target cells (primary cells or cell lines) with intact peptide-MHC presentation, or cells loaded with peptides such that natural peptide-MHC levels are achieved. Each support may comprise a marker that allows it to be detected once attached by determining the presence or absence of a signal generated by said marker. For example, the support may be labeled with a fluorescent dye or any other suitable cell labeling molecule. Such marker molecules are well known in the art. For example in the case of fluorescence labeling, such as that facilitated by a fluorescent dye, visualization of the bound aptamer can be achieved by fluorescence or laser scanning microscopy or by flow cytometry. Each support can be conjugated with a second active molecule, such as IL-21, anti-CD3 and anti-CD28. For more information on polypeptide supports see, for example, the general information section of WO201 4 / 071 978A1 and the references cited therein. The present invention also relates to aptamers. Aptamers (see for example WO 2014 / 191359 and the literature cited therein) are short single-stranded nucleic acid molecules, which can be folded into defined three-dimensional structures and which recognize specific target structures. They appear to be suitable alternatives for the development of targeted therapies. Aptamers have demonstrated selective binding to a range of complex targets with high affinity and specificity. In the past decade, aptamers have been discovered that recognize molecules located on the cell surface that constitute a means for the development of diagnostic and therapeutic strategies. The toxicity and immunogenicity of aptamers are, as far as n / ccnn / zznz / E / YiAi is known, practically zero, making them promising candidates for biomedical applications. And they are aptamers, for example aptamers that recognize the prostate-specific membrane antigen, which have been successfully used in targeted therapies and have demonstrated their functionality in in vivo xenograft models. In addition, aptamers have been discovered that recognize specific tumor cell lines. DNA aptamers can be selected to reveal broad-spectrum recognition properties against various cancer cells, and particularly those derived from solid tumors, while primary healthy, non-oncogenic cells are not recognized. If the discovered aptamers recognized not only a specific tumor subtype but also interacted with a series of tumors, they would become an applicable tool for broad-spectrum diagnosis and therapeutics. Furthermore, investigations of their binding to cells using flow cytometry have shown that aptamers have excellent apparent affinity at the nanomolar scale. Aptamers are useful for diagnostic and therapeutic purposes. Furthermore, it has been possible to demonstrate that some aptamers are taken up by tumor cells and can act as molecular vehicles for the targeted delivery of chemotherapeutic agents such as siRNA into tumor cells. Aptamers can be selected that are directed against complex targets such as cells and tissues and peptide complexes that comprise, and preferably consist of, a sequence according to any of SEQ ID NO. 1 to SEQ ID NO. 7, according to the claim with the MHC molecule, using the cell-SELEX technique (acronym for Systematic Evolution of Ligands by Exponential enrichment). The peptides of the present invention can be used to generate and develop specific antibodies against MHC / peptide complexes. These can be used as therapy, directing toxins or radioactive substances against diseased tissue. Another application of these antibodies would be to direct radionuclides against diseased tissue in imaging applications such as PET. This use can help detect small metastases or determine the size and precise location of diseased tissues. Therefore, there is another aspect of the invention that provides a method of producing a recombinant antibody that specifically binds to a human major histocompatibility complex (MHC) class I or II that forms a complex with an HLA-restricted antigen, comprising said method: immunizing a genetically modified non-human mammal comprising cells expressing said human major histocompatibility complex (MHC) class I or II with a soluble form of an MHC class I or II molecule linked to said HLA-restricted antigen; isolation of mRNA molecules from antibody-producing cells of said non-human mammal; production of a phage library containing protein molecules encoded by said mRNA molecules; and isolation of at least one phage from said phage library, wherein at least said phage contains said antibody that specifically binds to said human major histocompatibility complex (MHC) class I or II bound to said HLA-restricted antigen. There is a further aspect of the invention that provides an antibody that specifically binds to a human major histocompatibility complex (MHC) class I or II that forms a complex with an HLA-restricted antigen, wherein the antibody is preferably an antibody polyclonal, monoclonal antibody, bispecific antibody and / or a chimeric antibody. In WO 03 / 068201, WO 2004 / 084798, WO 01 / 72768, WO 03 / 070752, and in publications (Cohén et al., 2003a; Cohén et al., 2003b; Denkberg et al., 2003) are disclosed methods for producing such antibodies and single-chain class I major histocompatibility complexes, as well as other tools for the production of such antibodies, which for the purposes of the present invention are all explicitly incorporated in their entirety. Preferably the antibody binds to the complex with a binding affinity of less than 20 nanomolar, preferably less than 10 n / ccnn / zznz / E / YiAi nanomolar, which is considered "specific" in the context of the present invention. The present invention relates to a peptide comprising a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 67, or to a variant thereof that is at least 88% homologous (preferably identical) to SEQ ID NO. 1 to SEQ ID NO. 67 or a variant thereof that induces cross-reaction of T lymphocytes with said peptide, wherein said peptide is not an underlying entire polypeptide. The present invention further relates to a peptide comprising a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 67 or a variant thereof that is at least 88% homologous (preferably identical) to SEQ ID NO. 1 to SEQ ID NO. 67, wherein said peptide or variant has a total length of 8 to 100, preferably 8 to 30, and more preferably 8 to 14 amino acids. The present invention further relates to peptides according to the present invention that have the ability to bind to a major human histocompatibility complex (MHC) class I or II molecule. The present invention further relates to peptides according to the present invention wherein the peptide consists or consists essentially of an amino acid sequence according to SEQ ID NO. 1 to SEQ ID NO. 67. The present invention further relates to peptides according to the present invention, wherein said peptides are (chemically) modified and / or include non-peptide bonds. The present invention further relates to the peptides according to the present invention, wherein said peptides are part of a fusion protein, in particular they comprise N-terminal amino acids of the invariant chain associated with the HLA-DR antigen (1), or wherein the peptide is fused to (or in the sequence of) an antibody, such as, for example, an antibody that is specific for dendritic cells. The present invention further relates to a nucleic acid, n / ccnn / zznz / Ε / γΐΛΐ 100 that encodes the peptides according to the present invention, provided that the peptide is not the complete (whole) human protein. The present invention further relates to the nucleic acid according to the present invention which is DNA, cDNA, PNA, RNA or combinations of the above. The present invention further relates to an expression vector capable of expressing a nucleic acid according to the present invention. The present invention further relates to a peptide according to the present invention, a nucleic acid according to the present invention or an expression vector according to the present invention for use in medicine, in particular for the treatment of pancreatic cancer. The present invention further relates to a host cell comprising a nucleic acid according to the present invention or an expression vector according to the invention. The present invention further relates to a host cell according to the present invention which is an antigen-presenting cell, and preferably a dendritic cell. The present invention further relates to a method for producing a peptide according to the present invention, comprising culturing the host cell according to the present invention and isolating the peptide from the host cell or its medium. crop. The present invention further relates to the method according to the present invention wherein the antigen is loaded onto MHC class I or II molecules expressed on the surface of an antigen-presenting cell by contacting a sufficient amount of antigen with an antigen-presenting cell. The present invention further relates to the method according to the invention, wherein the antigen-presenting cell comprises an expression vector capable of expressing said peptide containing SEQ ID NO. 1 to SEQ ID NO. 67, or a variant of said amino acid sequence. n / ccnn / zznz / Ε / γΐΛΐ 101 The present invention further relates to activated T lymphocytes, produced with the method according to the present invention, which selectively recognize a cell expressing a polypeptide comprising an amino acid sequence according to the present invention. The present invention further relates to a method for destroying target cells in a patient whose target cells aberrantly express a polypeptide comprising any of the amino acid sequences according to the present invention, the method comprising administration to the patient. of an effective number of T lymphocytes according to the present invention. The present invention also relates to the use as a medicine or in the process of manufacturing a medicine of any of the described peptides, of a nucleic acid according to the present invention, of an expression vector according to the present invention , of a cell according to the present invention, or of an activated cytotoxic T lymphocyte according to the present invention. The present invention further relates to a use according to the present invention in which the medicament is active against cancer. The present invention further relates to a use according to the present invention in which said medicament is a vaccine. The present invention further relates to a use according to the invention in which the medicament is active against cancer. The present invention further relates to the use according to the invention, wherein said tumor cells are pancreatic cancer cells or other solid or hematological tumor cells such as pancreatic cancer, brain cancer, kidney cancer, kidney cancer. colon or rectum, or leukemia. The present invention also relates to specific marker proteins and biomarkers based on the peptides according to the present invention, here called "targets" that can be used for the diagnosis and / or prognosis of pancreatic cancer. Furthermore, the present invention relates to the use of these new targets for the treatment of cancer. n / ccnn / zznz / E / YiAi 102 The term “antibody” or “antibodies” is used herein broadly and includes both polyclonal and monoclonal antibodies. In addition to intact or “whole” immunoglobulin molecules, the term “antibodies” also includes fragments (e.g., CDRs, Fv, Fab and Fe fragments) or polymers of those immunoglobulin molecules and humanized versions thereof, provided that exhibit any of the desired properties (for example, specific binding of a pancreatic cancer marker polypeptide, release of a toxin in a pancreatic cancer cell that expresses a cancer marker gene at a high level, and / or inhibits the activity of a pancreatic cancer marker polypeptide) according to the invention. If possible, the antibodies of the invention can be purchased from commercial sources. The antibodies of the invention can also be made with known methods. The person skilled in the art understands that both whole pancreatic cancer marker polypeptides and fragments thereof can be used to prepare the antibodies of the invention. The polypeptide necessary to generate an antibody of the invention can be partially or completely purified from a natural source or can be produced with recombinant DNA techniques. For example, a cDNA encoding a peptide according to the present invention, such as a peptide according to the polypeptide of SEQ ID NO. 1 to SEO ID NO. 67, or a variant or fragment thereof, can be expressed in prokaryotic (for example, bacteria) or eukaryotic (for example, yeast, insect or mammalian cells), from which the recombinant protein will be purified with the that a monoclonal or polyclonal antibody preparation will be generated that specifically binds to the pancreatic cancer marker polypeptide used to generate the antibody according to the invention. A person skilled in the art will know that the generation of two or more different sets of monoclonal or polyclonal antibodies maximizes the probability of obtaining an antibody having the specificity and affinity necessary for the intended use (by n / ccnn / zznz / E / YiAi 103 example, ELISA, immunohistochemistry, in vivo imaging techniques, immunotoxin treatment). The antibodies are analyzed for the desired activity with known methods, according to the intended purpose of the antibodies (e.g. ELISA, immunohistochemistry, immunotherapy, etc.; for more details on antibody generation and analysis, see e.g. , Greenfield, 2014 (Greenfield, 2014). For example, antibodies can be analyzed with ELISA tests, Western blot, immunohistochemical staining of frozen or formalin-fixed cancer tissue sections. After initial in vitro characterization, Antibodies intended for therapeutic or diagnostic use in vivo are tested with known clinical test methods. The term "monoclonal antibody" as used herein refers to an antibody obtained from a remarkably homogeneous population of antibodies, that is, the individual antibodies comprising the population are identical except for possibly naturally occurring mutations that may be present in small numbers. Monoclonal antibodies herein specifically include "chimeric" antibodies in which a portion of the heavy and / or light chain is identical or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular class or subclass of antibodies. , while the rest of the chain or chains is identical or homologous to corresponding sequences in antibodies derived from other species or belonging to another class or subclass of antibodies, as well as to fragments of such antibodies, as long as they exhibit the desired antagonistic activity ( United States Patent No. 4,816,567, which is incorporated herein in its entirety). The monoclonal antibodies of the invention can be prepared with hybridoma-based methods. In the hybridoma method, a mouse or other suitable host animal is vaccinated with an immunizing agent that stimulates lymphocytes to produce or be capable of producing antibodies that specifically bind to the immunizing agent. Another alternative is to immunize lymphocytes in n / ccnn / zznz / Ε / γΐΛΐ 104 vi tro. Monoclonal antibodies can also be made with recombinant DNA methods, such as those described in US Patent No. 4,816,567. The DNA encoding the monoclonal antibodies of the invention can be easily isolated and sequenced with conventional procedures (for example, with oligonucleotide probes capable of specifically binding to the genes encoding the heavy and light chains of mouse antibodies). In vitro methods are also suitable for the preparation of monovalent antibodies. Digestion of antibodies to produce fragments thereof, particularly Fab fragments, can be carried out with ordinary techniques known to those skilled in the art. For example, digestion can be done with papain. Examples of papain digestion are described in WO 94 / 29348 and in US Patent No. 4,342,566. Digestion of antibodies with papain typically produces two identical antigen-binding fragments called Fab fragments, each endowed with an antigen-binding site, as well as a residual Fe fragment. Treatment with pepsin results in an F(ab') fragment. )2 and another fragment pFc'. Antibody fragments, whether linked to other sequences or not, may also include insertions, deletions, substitutions and other selected modifications of particular regions or of specific amino acid residues, provided that the activity of the fragments is not significantly altered or affected with respect to to the intact antibody or antibody fragment. These modifications may offer some additional properties, such as eliminating or adding amino acids capable of establishing sulfur bridges to increase biolongevity, alter secretion characteristics, etc. In any case, the antibody fragment must possess a bioactive property, such as binding activity, regulation of binding to the binding domain, etc. Active or functional regions of the antibody can be identified by mutagenesis of a specific region of the protein, followed by expression and analysis of the expressed polypeptide. Such n / ccnn / zznz / E / YiAi 105 methods are obvious to one skilled in the art and may include targeted mutagenesis of the nucleic acid encoding the antibody fragment. Antibodies of the invention may also comprise humanized antibodies or human antibodies. Humanized forms of non-human (e.g., mouse) antibodies are chimeric forms of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab' or other antigen-binding sequences of antibodies) that They contain a small sequence derived from non-human immunoglobulins. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues of a complementarity determining region (CDR) of the recipient are replaced by residues of a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit that is endowed with the desired specificity, affinity and capacity. In some cases, the structural residues (FR) of the Fv fragment of human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues that are not present in either the recipient antibody or the imported CDR or structural sequences. In general, the humanized antibody will comprise substantially all of at least one, and usually two, variable domains, in which all or nearly all of the CDR regions will correspond to those of the non-human immunoglobulin and all or nearly all of the FR regions will be those of the non-human immunoglobulin. of a consensus sequence of human immunoglobulin. The humanized antibody will ideally also comprise at least a portion of an immunoglobulin constant region (Fe), typically of a human immunoglobulin. Methods for humanizing non-human antibodies are well known in the art. In general, a humanized antibody has one or more amino acid residues of non-human origin. These non-human amino acid residues are often referred to as “import” residues, which are typically extracted from the “import” variable domain. Humanization can basically be carried out by replacing rodent CDRs or CDR sequences with n / ccnn / zznz / E / YiAi 106 corresponding sequences of a human antibody. Therefore, such “humanized” antibodies are chimeric antibodies (U.S. Patent No. 4,816,567), in which a notably smaller portion of an intact human variable domain has been replaced by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues have been replaced by residues from analogous sites in rodent antibodies. Transgenic animals (for example, mice) can be used that after immunization are capable of producing a complete repertoire of human antibodies without producing endogenous immunoglobulins. For example, homozygous deletion of the antibody heavy chain binding region gene in chimeric and germline mutant mice has been reported to result in complete inhibition of endogenous antibody production. Transfer of the human germline immunoglobulin gene array to such germline mutant mice will result in the production of human antibodies upon exposure to the antigen. Human antibodies can also be produced in phage libraries. The antibodies of the invention are preferably administered to a subject by incorporating them into a pharmaceutically acceptable carrier. Normally an appropriate amount of a pharmaceutically acceptable salt is added to the formulation to make it isotonic. Examples of pharmaceutically acceptable carriers are saline, Ringer's solution and dextrose solution. It is preferable that the pH of the solution is between about 5 and 8, and more preferably between about 7 and 7.5. Other carriers include sustained release preparations such as semipermeable matrices of solid hydrophobic polymers containing the antibody, in shaped matrices, for example, films, liposomes or microparticles. It will be apparent to those skilled in the art that certain vehicles are preferable depending, for example, on the route of administration and the concentration of the antibody to be administered. n / ccnn / zznz / Ε / γΐΛΐ 107 Antibodies can be administered to the subject, patient or cells by injection (intravenous, intraperitoneal, subcutaneous, intramuscular, etc.), or with other methods such as infusion that ensure their effective release into the bloodstream. Antibodies can also be administered intratumorally or peritumorally to exert a systemic and local therapeutic effect. Local or intravenous injection is preferred. The most appropriate doses and administration schedules can be determined empirically; Decision making in this regard is part of the knowledge of the subject. Those skilled in the art know that the dose of antibodies to be administered depends, for example, on the subject who is going to receive the antibody, the route of administration, the specific type of antibody and other medications that are being administered. The typical daily dose of antibody when used alone may range from 1 pg / kg to 100 mg / kg body weight or more per day, depending on the above factors. Following administration of the antibody, preferably for the treatment of pancreatic cancer, the efficacy of the therapeutic antibody can be evaluated in several ways well known to the skilled physician. For example, the size, number and / or distribution of cancer in the subject receiving treatment can be monitored using standard oncological imaging techniques. Any antibody administered for therapeutic purposes that stops tumor growth, reduces its extension and / or prevents the appearance of new tumors in contrast to the evolution of the disease if the administration of the antibody did not occur, is an effective antibody for the treatment of cancer. Another aspect of the invention provides a method of producing a soluble T cell receptor (sTCR) that recognizes a specific peptide-MHC complex. Such soluble T cell receptors can be generated from specific T cell clones, whose affinity can be increased by targeted mutagenesis to the complementarity-determining regions. A phage library can be used to select the T cell receptor (US 2010 / 01 13300, (Liddy et al., 2012)). In order to stabilize the T cell receptors in the phage library and in case of practical use as a drug, the alpha and n / ccnn / zznz / E / YiAi chains 108 beta can be linked for example through non-native disulfide bonds, other covalent bonds (single-chain T cell receptor), or through dimerization domains (Boulter et al., 2003; Card et al., 2004; Willcox et al., 1999 ). The T cell receptor can bind to toxins, drugs, cytokines (see, for example, US 2013 / 0115191) and domains that recruit effector cells such as an anti-CD3 domain, etc., in order to execute particular functions in cells. Diana. Likewise, it can be expressed in T lymphocytes destined for transfer to a recipient. More information can be found in WO 2004 / 033685A1 and WO 2004 / 074322A1. A combination of sTCR is described in WO 2012 / 056407A1. Other production methods are disclosed in WO 201 3 / 057586A1. Furthermore, the peptides and / or TCRs or antibodies or other binding molecules of the present invention can be used to verify the histopathological diagnosis of cancer based on a biopsy sample. Antibodies or TCRs can also be used for in vivo diagnostic assays. Generally, the antibody is labeled with a radionuclide (such as 1111n, Te, 14C, 131l, 3H, 32P, or 35S) so that the tumor can be localized with immunoscintigraphy. In one embodiment, antibodies or fragments thereof bind to the extracellular domains of two or more targets of a protein selected from the group consisting of the aforementioned proteins, and the affinity value (Kd) is less than 1 x 10 μΜ. Antibodies for diagnostic use can be labeled with suitable probes to enable detection with different optical methods. Methods for probe detection include, but are not limited to, fluorescence, optical, confocal, and electron microscopy; magnetic resonance and spectroscopy; fluoroscopy, computed tomography and positron emission tomography. Suitable probes include, but are not limited to, fluorescein, rhodamine, eosin and other fluorophores, radioisotopes, gold, gadolinium and other lanthanides, paramagnetic iron, fluorine-18 and other positron-emitting radionuclides. Furthermore, the probes may be bi- or multifunctional and detectable by more than one of the methods listed. Antibodies can be marked n / ccnn / zznz / Ε / γΐΛΐ 109 directly or indirectly with said probes. Attachment of probes to antibodies includes covalent attachment of the probe, incorporation of the probe into the antibody, and covalent attachment of a chelating compound to bind the probe, among other methods known in the art. For immunohistochemistry techniques, the pathological tissue sample can be fresh or frozen or can be embedded in paraffin and fixed with a preservative such as formalin. The fixed or embedded section containing the sample is contacted with a labeled primary antibody and a secondary antibody, so that the antibody is used to detect in situ expression of the proteins. Another aspect of the present invention includes an in vitro method for producing activated T lymphocytes, said method comprising contacting T lymphocytes under in vitro conditions with antigen-loaded human MHC molecules expressed on the surface of a suitable antigen-presenting cell for time. sufficient to activate T lymphocytes in an antigen-specific manner, the antigen being a peptide according to the invention. Preferably a sufficient amount of the antigen is used with an antigen-presenting cell. Preferably, the mammalian cell lacks the TAP peptide transporter or is present at a reduced level or functions defectively. Suitable cells lacking the TAP peptide transporter include T2, RMA-S and Drosophila cells. TAP is the transporter related to antigen processing. The T2 peptide loading-deficient human cell line is available from the American Type Culture Collection, 12301 Parklawn Drive, Rockville, Maryland 20852, USA under catalog number CRL 1992; Drosophila Schneider line 2 cell line is available from ATCC under catalog number CRL 19863; The mouse cell line RMA-S is described in Ljunggren and collaborators (Ljunggren and Karre, 1985). Preferably, the host cell does not substantially express MHC class I molecules prior to transfection. It's also n / ccnn / zznz / E / YiAi Preferably, the stimulatory cell expresses an important molecule that provides a costimulatory signal for T cells, such as B7. 1, B7. 2, ICAM-1 and LFA 3. Nucleic acid sequences of numerous MHC class I molecules and costimulatory molecules are publicly available in the GenBank and EMBL databases. If an MHC class I epitope is used as the antigen, the T cells will be CD8-positive T cells. If an antigen-presenting cell is transfected to express such an epitope, the cell will preferably comprise an expression vector capable of expressing a peptide containing SEQ ID NO. 1 to SEQ ID NO. 67, or a variant amino acid sequence thereof. There are other methods to generate T lymphocytes in vitro. For example, using autologous lymphocytes infiltrated in the tumor to generate CTL. Plebanski and collaborators (Plebanski et al., 1995) use autologous peripheral blood lymphocytes (PLB) for the preparation of T lymphocytes. Likewise, the production of autologous T lymphocytes is possible by stimulating dendritic cells with the peptide or polypeptide, or by through infection with recombinant viruses. B cells can also be used for the production of autologous T cells. Likewise, macrophages stimulated with peptide or polypeptide or infected with recombinant viruses can be used for the preparation of autologous T lymphocytes. S. Walter and collaborators (Walter et al., 2003) describe in vitro priming of T cells using artificial antigen-presenting cells (aAPCs), which is another suitable way to generate T cells against the peptide of choice. In the present invention, aAPCs were generated by attaching preformed MHC:peptide complexes to the surface of polystyrene particles (microbeads) with biotin:streptavidin. This system allows the exact control of MHC density on aAPCs, allowing the triggering of antigen-specific T cell responses with high or low avidity from blood samples, in a selective and highly efficient manner. In addition to MHC:peptide complexes, aAPCs must incorporate n / ccnn / zznz / E / YiAi coupled to their surface. 111 other proteins with co-stimulatory activity such as antiCD28 antibodies. Such aAPC systems often also require the participation of suitable soluble factors, for example cytokines, such as interleukin-1 2. Allogeneic cells can also be used to prepare T lymphocytes; A method is described in detail in WO 97 / 26328 and is incorporated herein by reference. For example, in addition to Drosophila cells and T2 cells, other cells such as CHO cells, baculovirus-infected insect cells, bacteria, yeast, and vaccinia virus-infected target cells can be used to present antigens. Plant viruses can also be used (see for example Porta et al. (Porta et al., 1994), who describe the development of the pea mosaic virus as a high-throughput system for the presentation of foreign peptides). Activated T cells that are directed against the peptides of the invention are useful as a treatment. Thus, another aspect of the invention provides activated T lymphocytes obtainable by the aforementioned methods of the invention. Activated T lymphocytes produced with the aforementioned method will selectively recognize a cell that aberrantly expresses a polypeptide comprising an amino acid sequence of SEQ ID NO. 1 to SEQ ID NO. 67. Preferably, the T lymphocyte recognizes the cell by interacting through its TCR with the HLA / peptide complex, for example by binding to it. T cells are useful in a method of destroying target cells in a patient whose target cells aberrantly express a polypeptide comprising an amino acid sequence of the invention and to whom an effective number of activated T cells is administered. The T lymphocytes administered can come from the same patient and be activated in the manner described above, that is, they can be autologous T lymphocytes. Another alternative is that the T lymphocytes are not from the patient and come from another individual. Of course, it is preferable that said individual be healthy. By “healthy individual” the inventors mean an individual who is in good health n / ccnn / zznz / E / YiAi 112 generally, preferably with a competent immune system and, more preferably, not suffering from any disease that can be detected by testing. Under in vivo conditions, the target cells of CD8-positive T lymphocytes according to the present invention can be tumor cells (which sometimes express MHC class II) and / or stromal cells surrounding the tumor (tumor cells) (which sometimes They also express MHC class II (Dengjel et al., 2006). The T lymphocytes of the present invention can be used as active ingredients of a therapeutic composition. Therefore, the invention also provides a method for destroying target cells of a patient that aberrantly express a polypeptide comprising an amino acid sequence of the invention, said method comprising administering to the patient an effective number of T lymphocytes such as defined above. By "aberrantly expressed" the inventors also mean that the polypeptide is overexpressed compared to normal levels of expression or that the gene is repressed in the tissue from which the tumor derives but is instead expressed in it. By "overexpressed" the inventors mean that the level of the polypeptide is at least 1.2 times higher than the level in normal tissue; preferably at least 2 times greater, and more preferably at least 5 or 10 times greater than that of normal tissue. T lymphocytes can be obtained by methods known in the art, such as, for example, those described above. The protocols for the so-called transfer of T lymphocytes to a recipient are perfectly known. Reviews can be found in: Gattioni et al. and in Morgan et al. (Gattinoni et al., 2006; Morgan et al., 2006). Another aspect of the present invention includes the use of the peptides complexed with MHC to generate a T cell receptor whose nucleic acid is cloned and introduced into a host cell, preferably a T cell. That modified T cell can then be transferred to a patient as a treatment against n / ccnn / zznz / Ε / γΐΛΐ 113 cancer. Any molecule of the invention, whether peptide, nucleic acid, antibody, expression vector, cell, activated T cell, T cell receptor or the nucleic acid that encodes it, is useful for the treatment of disorders characterized by cells that evade the response. immune. Consequently, any molecule of the present invention can be used as a medicine or in the preparation of a medicine. The molecule can be used alone or combined with another molecule or molecules of the invention or with any known molecule or molecules. The present invention provides a medicament that is useful for the treatment of cancer, particularly pancreatic cancer and other malignancies. The present invention also contemplates equipment that comprises: (a) a container with a pharmaceutical composition as described above, in solution or freeze-dried form; (b) optionally, a second container containing a diluent or reconstitution solution for the lyophilized formulation; and (c) optionally, (I) instructions for use of the solution or (II) reconstitution and / or use of the lyophilized formulation. The kit may further comprise one or more of the following components: (III) a buffer, (IV) a diluent, (V) a filter, (VI) a needle, or (V) a syringe. The container is preferably a bottle, vial, syringe or test tube; It can be a multipurpose container. It is preferred that the pharmaceutical composition be lyophilized. The kits of the present invention preferably comprise a lyophilized formulation of the present invention in a suitable container and instructions for its reconstitution and / or use. Suitable containers include, for example, bottles, vials (for example, double chamber vials), syringes (such as double chamber syringes) and test tubes. The container can be made of various materials such as glass or plastic. Preferably the kit and / or container contain or are accompanied by instructions for reconstitution and / or use. For example, the package insert may indicate that the formulation n / ccnn / zznz / E / YiAi Lyophilized 114 must be reconstituted to obtain certain concentrations of peptides such as those described on preceding pages. The label may further indicate that the formulation may be administered or is intended for subcutaneous administration. The container containing the formulation may be a multi-use vial that allows for multiple administrations (e.g., 2 to 6 administrations) of the reconstituted formulation. The kit may further comprise a second container containing a suitable diluent (for example, a sodium bicarbonate solution). After mixing the diluent and the lyophilized formulation, the final concentration of the peptide in the reconstituted formulation is preferably at least 0.15 mg / ml / peptide (= 75 pg) and preferably at most 3 mg / ml / peptide (= 1500 pg). ). The kit may also include other commercially and user-desirable materials, such as other buffers, diluents, filters, needles, syringes, and package inserts with instructions for use. The kits of the present invention may have a single container that contains the formulation of the pharmaceutical compositions according to the present invention, accompanied or not by other components (for example, other compounds or pharmaceutical compositions of these other compounds) or they may have a different container for each component. Preferably, the kits of the invention include a formulation of the invention adapted to be used and administered together with a second compound (such as adjuvants (for example, GM-CSF), a chemotherapy agent, a natural product, a hormone or an antagonist , an anti-angiogenesis inhibitor or agent, an apoptosis inducer or a chelator) or a pharmaceutical composition thereof. The components of the kit may be pregrouped or each component may be in a separate container prior to administration to the patient. The components of the kit may be provided in one or more liquid solutions, preferably in an aqueous solution and, more preferably, in a sterile aqueous solution. Equipment components may also be provided in solid form, and may n / ccnn / zznz / E / YiAi 115 converted into liquids by adding the appropriate solvents, which are preferably provided in a separate container. The container of a therapeutic device may be a vial, test tube, flask, bottle, syringe, or any other means of containing a solid or liquid. If there is more than one component, the kit will normally contain a second vial or other container to allow separate dosing. The kit may also contain another container for a pharmaceutically acceptable liquid. Preferably the therapeutic kit will contain an apparatus (for example, one or more needles, syringes, dropper, pipette, etc.) to allow the administration of the agents of the invention that are components of the present kit. The present formulation can be any that is suitable for the administration of the peptides through any acceptable route such as oral (enteral), nasal, ophthalmic, subcutaneous, intradermal, intramuscular, intravenous or transdermal. Subcutaneous administration is preferred and, more preferably, intradermal perhaps via an infusion pump. Since the peptides of the invention come from tumor tissue related to pancreatic cancer, the drug of the invention is preferably used to treat pancreatic cancer. The present invention further relates to a method for producing a personalized pharmaceutical product for a specific patient, which comprises the preparation of a pharmaceutical composition consisting of at least one peptide chosen from a file (database) of preselected TUMAPs, wherein at least one peptide of the pharmaceutical composition is selected for its suitability for that patient. In one embodiment, the pharmaceutical composition is a vaccine. The method can also be adapted to produce T lymphocyte clones for applications aimed at obtaining the finished product, such as the isolation of TCR, or soluble antibodies and other treatment options. A “personalized pharmaceutical product” specifically means therapies personalized for a patient that will only be used to treat them, such as personalized cancer vaccines and adoptive cellular therapies using the patient's autologous tissue. n / ccnn / zznz / E / YiAi 116 As used herein, the term “warehouse” designates a group of peptides that have been preselected for their immunogenicity and / or overpresentation in a specific type of tumor. The term “file” does not imply that the specific peptides included in the vaccine have been pre-made and stored in a physical location, although it does consider that possibility. It is expressly contemplated that the peptides can be made de novo for each individualized vaccine produced, or that they can be pre-made and stored. The archive (for example, in the form of a database) is composed of tumor-associated peptides that are strongly overexpressed in the tumor tissue of pancreatic cancer patients carrying various HLA-A, HLA-B and HLA-C alleles. . It may contain MHC class I and class II peptides or elongated MHC class I peptides. In addition to tumor-associated peptides obtained from various pancreatic cancer tissues, the file may contain HLA-A*02 and HLA marker peptides. -A*24. These peptides allow us to quantitatively compare the magnitude of T cell-dependent immunity induced by TUMAPs and, consequently, to draw important conclusions about the vaccine's ability to trigger antitumor responses. Second, they act as important positive control peptides from an exogenous antigen in the event that no vaccine-induced T cell response is observed against TUMAPs derived from patient autoantigens. And third, it sometimes allows conclusions to be drawn regarding the patient's immunocompetence status. TUMAPs in the archive are identified through a strategy that combines integrated functional genomics with gene expression analysis, mass spectrometry and T cell immunology (XPresident®). The strategy ensures that only TUMAPs actually present in a high percentage of tumors are chosen to continue the analysis, discarding those that are not expressed or do so very little in normal tissue. For the selection of the initial peptide, pancreatic cancer samples from patients and blood taken from healthy donors were analyzed in a stepwise manner: n / ccnn / zznz / E / YiAi 117 1. The HLA ligands of the cancerous material were identified with mass spectrometry. 2. A genome-wide analysis of messenger ribonucleic acid (mRNA) expression was performed to discover genes that were overexpressed in malignant tissue (pancreatic cancer) compared to a range of normal organs and tissues. 3. The identified HLA ligands were compared with gene expression data. Peptides overexpressed or selectively expressed by the tumor tissue, preferably those encoded by overexpressed or selectively expressed genes such as those detected in the second step were considered TUMAP candidates for the multipeptide vaccine. 4. A literature search was carried out to find additional data that supported the relevance of the peptides identified as TUMAP. 5. The relevance of the overexpression at the mRNA level was confirmed by re-detecting the TUMAPs selected in step 3 in the tumor tissue and verifying that they were not detected (or very little) in the healthy tissues 6. To evaluate whether the selected peptides were likely to induce T cell responses in vivo, in vitro immunogenicity tests were carried out with human T cells from healthy donors and patients with pancreatic cancer. In another aspect, peptides are preselected for their immunogenicity before being included in the file. By way of example and without limitation, the immunogenicity of the peptides included in the file is determined with a method that involves the repeated in vitro stimulation of CD8 + T lymphocytes from healthy donors with artificial antigen-presenting cells loaded with the peptide complexes. / MHC and anti-CD28 antibody. This method is preferred for rare cancers and patients with an unusual expression profile. In contrast to the fixed composition multipeptide cocktails being developed the file allows for significantly higher concordance of the n / ccnn / zznz / E / YiAi 118 real expression of antigens in the tumor with the vaccine. One peptide or combinations of several off-the-shelf peptides can be used for each patient as part of a multitarget strategy. In theory, a strategy based on the selection of, say, 5 different antigenic peptides from a library of 50 would generate about 17 million possible pharmaceutical compositions. In one aspect, peptides are selected for inclusion in the vaccine based on their suitability for each patient according to a method according to the present invention, as set forth herein and below. HLA phenotype, transcriptomic, and peptidomic data are collected from tumor material and patient blood samples to identify the most suitable TUMAP-containing peptides contained in the “file” and unique to the patient (i.e., mutated). Peptides will be chosen that are selectively expressed or overexpressed in the patient's tumor and, if possible, that exhibit potent immunogenicity in vitro if tested with the patient's PBMC. Preferably, the peptides included in the vaccine will be identified with the method consisting of: (a) identification of tumor-associated peptides (TUMAP) present in a tumor sample from the patient in question; (b) comparison of the identified peptides with (a) a peptide file (database) as described above; and (c) selection of at least one peptide from the database that presents a correlation with a tumor-associated peptide identified in the patient. For example, TUMAPs presented by the tumor sample are identified by: (a1) comparing the expression data of the tumor sample with the expression data of a normal tissue sample of the same tissue type of the tumor sample to identify proteins that are overexpressed or aberrantly expressed in the tumor sample; and (a2) correlation of the expression data with sequences of MHC ligands bound to MHC class I and / or class II molecules in the tumor sample to identify MHC ligands derived from proteins that are overexpressed or aberrantly expressed by the tumor. Preferably, the sequences of the MHC ligands are n / ccnn / zznz / E / YiAi 119 identify by eluting the bound peptides from the MHC molecules isolated from the tumor sample and sequencing the eluted ligands. Preferably, the tumor sample and the normal tissue are obtained from the same patient. In addition to, or as an alternative to, peptide selection using the database model, TUMAPs can also be identified in the patient de novo and then included in the vaccine. As an example, candidate TUMAPs can be identified in the patient by (a) comparing the expression data of the tumor sample with the expression data of a normal tissue sample that corresponds to the tissue type of the tumor sample to identify proteins that are overexpressed or aberrantly expressed in the tumor sample; and (a2) correlation of the expression data with sequences of MHC ligands bound to MHC class I and / or class II molecules in the tumor sample to identify MHC ligands derived from proteins that are overexpressed or aberrantly expressed by the tumor. As another example, proteins carrying mutations that are unique to the tumor sample can be identified compared to the corresponding normal tissue of the patient, as well as TUMAPs that allow the mutation to be specifically recognized. For example, the genome of the tumor and that of the corresponding normal tissue can be sequenced by whole-genome sequencing: To discover non-synonymous mutations in the protein-coding regions of genes, genomic DNA and RNA are extracted from tissues. tumor cells and normal and non-mutated germline genomic DNA from peripheral blood mononuclear cells (PBMC). The next generation sequencing (NGS) strategy applied is limited to the re-sequencing of the protein coding regions (exorna re-sequencing). To this end, exonic DNA is captured from human samples with targeted enrichment kits supplied by the supplier and sequenced with, for example, an H¡Seq2000 sequencer (lllumina). Additionally, tumor mRNA is sequenced to determine direct quantification of gene expression and validation that the mutated genes are expressed in n / ccnn / zznz / E / YiAi tumors. 120 patient. The resulting millions of sequence reads are processed with computer algorithms. The results list contains mutations and gene expression. Tumor-specific somatic mutations are determined by comparing them with germline variations derived from PBMCs and prioritized. De novo identified peptides can be analyzed for immunogenicity as described above with the file, and candidate TUMAPs possessing appropriate immunogenicity are chosen for inclusion in the vaccine. In an exemplary embodiment, the peptides included in the vaccine are identified by: (a) identification of tumor-associated peptides (TUMAP) present in a tumor sample from the patient in question using the method described above; (b) comparison of the peptides identified in a) the archive (database) of peptides that have been preselected for their immunogenicity and their overpresentation in tumors compared to normal tissue; (c) selection of at least one peptide from the database that presents a correlation with a tumor-associated peptide identified in the patient; and (d) optionally, selection of at least one peptide identified de novo in step (a) to confirm its immunogenicity. In an exemplary embodiment, the peptides included in the vaccine are identified by: (a) identification of tumor-associated peptides (TUMAP) present in a tumor sample from the patient in question; and (b) optionally, selection of at least one peptide identified de novo in step (a) to confirm its immunogenicity. Once the peptides are chosen for the custom peptide-based vaccine, the vaccine is made. The vaccine preferably is a liquid formulation consisting of the individual peptides dissolved in between 20% and 40% DMSO, preferably in between 30% and 35% DMSO, such as about 33% DMSO. Each peptide is dissolved in DMSO before becoming part of the product. The concentration of each peptide solution is chosen depending on the number of peptides that will be part of the product. n / ccnn / zznz / E / YiAi 121 Each peptide and DMSO solution is mixed in equal parts to obtain a solution containing all peptides in the product with a concentration of ~2.5 mg / ml per peptide. The mixed solution is diluted 1:3 with water for injection to reach a concentration of 0.826 mg / ml per peptide in 33% DMSO. The diluted solution is filtered with a sterile 0.22 pm filter. The final bulk solution is obtained. The final bulk solution is packaged in vials and stored at -20°C until use. One vial contains 700 μΙ of solution containing 0.578 mg of each peptide. Of which 500 μΙ (approx. 400 μg per peptide) will be applied with the intradermal injection. In addition to being useful for the treatment of cancer, the peptides of the present invention are also useful for diagnosis. Since the peptides are generated by pancreatic cancer cells and it has been determined that said peptides are not present or are present at low levels in normal tissues, said peptides can be used to diagnose the presence of cancer. The presence of the claimed peptides in tissue biopsies can help the histopathologist diagnose cancer. Detection of certain peptides by antibodies, mass spectrometry or other methods known in the art can alert the histopathologist that the sample is malignant or inflamed or diseased in general, or can be used as a biomarker for pancreatic cancer. The presence of groups of peptides may allow classification or subclassification of diseased tissues. Detection of the peptides in a sample of diseased tissue can help decide whether treatments that involve the immune system may be beneficial, especially if T cells are known or predicted to be involved in the mechanism of action. Loss of MHC expression is a known mechanism by which infected or cancerous cells manage to evade the surveillance of the immune system. Thus, the presence of the peptides indicates that this mechanism is not used by the cells analyzed. The peptides of the present invention can be used to analyze the responses of lymphocytes against them, such as n / ccnn / zznz / E / YiAi 122 T cell responses or antibody responses against the peptide or the peptide bound to MHC molecules. These lymphocyte responses can be used as prognostic markers to decide subsequent treatment steps. These responses can also be used as indirect markers in immunotherapy strategies aimed at stimulating lymphocyte responses through different means, such as vaccination with proteins, nucleic acids, autologous materials, or the transfer of donor lymphocytes. In the field of gene therapy, lymphocyte responses against peptides can be taken into account for the evaluation of side effects. Regular monitoring of lymphocyte responses may also be a valuable tool for transplant monitoring, for example to detect graft-versus-host and host-versus-graft diseases. The present invention will now be described with the following examples with reference to the attached figures that describe the preferred embodiments thereof, without intending to limit the invention. For purposes of the present invention, all references cited herein are incorporated by reference in their entirety. Figure 1A-C shows the overpresentation of several peptides in normal tissues (dark gray) and in pancreatic cancer (light gray). Figure 1D shows all cell lines (dark gray), normal tissues (gray) and cancerous tissues (light gray) where the example peptide (FLFDGSANLV) (SEQ ID NO. 9) has been detected. Figure 1 A) Gene: CTLA / CTLB, Peptide: FLAQQESEI(A*02) (SEQ ID NO. 1); Tissues shown from left to right: 1 adipose tissue, 3 adrenal glands, 2 arteries, 3 bone marrows, 7 brains, 3 breasts, 13 colons, 1 ovary, 4 esophagus, 2 gallbladders, 3 hearts, 12 kidneys, 4 samples of leukocytes, 19 livers, 43 lungs, 1 lymph node, 1 ovary, 2 peripheral nerves, 1 peritoneum, 1 pituitary gland, 3 pleurae, 1 prostate, 6 rectums, 3 skeletal muscles, 3 skins, 2 small intestines, 4 spleens, 5 stomachs , 1 testicle, 2 thymuses, 3 thyroid glands, 2 uteruses, 2 veins, 6 pancreas, n / ccnn / zznz / E / YiAi 123 pancreatic tumors; Figure 1 B) Gene: PLEC, Peptide: SLQEEHVAVA (A*02), (SEO ID NO. 2); Tissues shown from left to right: 1 adipose tissue, 3 adrenal glands, 2 arteries, 3 bone marrows, 7 brains, 3 breasts, 13 colons, 1 ovary, 4 esophagus, 2 gallbladders, 3 hearts, 12 kidneys, 4 samples of leukocytes, 19 livers, 43 lungs, 1 lymph node, 1 ovary, 2 peripheral nerves, 1 peritoneum, 1 pituitary gland, 3 pleurae, 1 prostate, 6 rectums, 3 skeletal muscles, 3 skins, 2 small intestines, 4 spleens, 5 stomachs , 1 n / ccnn / zznz / E / YiAi testicle, 2 thymuses, 3 thyroid glands, 2 uteri, 2 veins, 6 pancreas, 18 pancreatic tumors; Figure 1C) Gene: COL6A3, Peptide: FLVDGSSAL (A*02) (SEQ ID NO. 10); Tissues shown from left to right: 1 adipose tissue, 3 adrenal glands, 2 arteries, 3 bone marrows, 7 brains, 3 breasts, 13 colons, 1 ovary, 4 esophagus, 2 gallbladders, 3 hearts, 12 kidneys, 4 samples of leukocytes, 19 livers, 43 lungs, 1 lymph node, 1 ovary, 2 peripheral nerves, 1 peritoneum, 1 pituitary gland, 3 pleurae, 1 prostate, 6 rectums, 3 skeletal muscles, 3 skins, 2 small intestines, 4 spleens, 5 stomachs , 1 testicle, 2 thymuses, 3 thyroid glands, 2 uteruses, 2 veins, 6 pancreas, 18 pancreatic tumors; Figure 1 D) COL6A3, Peptide: FLFDGSANLV (A*02) (SEQ ID NO. 9); Tissues shown from left to right: 5 pancreatic cancer cell lines, 7 normal tissues (1 colon, 6 lungs), 85 cancerous tissues (2 breast cancers, 6 colon cancers, 4 esophageal cancers, 3 liver cancers, 56 lung cancers, 5 pancreatic cancers, 3 rectal cancers, 1 melanoma, 5 gastric cancers). The set of normal tissues was the same as in A-C, but tissues in which there was no detection are not shown. The discrepancies between the lists of tumor types in Figure 1D and Table 4 would be a consequence of the greater rigor applied in the selection criteria of the latter (for more details, see Table 4). Figure 1D shows a list of all the samples in which the presentation of peptide Y was detected, regardless of the overpresentation parameters and the technical quality control of the 124 sample. Figure 1E-I shows all cell lines (dark gray), normal tissues (gray) and tumor tissues (light gray) where all the peptides shown by way of example have been detected. Figure 1E) Peptide: SVDVSPPKV (A*02) (SEQ ID NO. 4); Tissues arranged from left to right: 1 cell line, 3 primary cultures, 1 skin, 1 bile duct cancer, 3 brain cancers, 1 breast cancer, 4 esophageal cancers, 5 kidney cancers, 11 lung cancers, 1 cancer lymph node, 1 ovarian cancer, 3 pancreatic cancers, 1 prostate cancer, 3 skin cancers, 2 urinary bladder cancers, 3 uterine cancers; Figure 1 F) Peptide: LLVDDSFLHTV (A*02) (SEQ ID NO. 5); Tissues arranged from left to right: 2 cell lines, 1 primary culture, 1 bile duct cancer, 2 brain cancers, 1 breast cancer, 3 esophageal cancers, 2 gallbladder cancers, 2 kidney cancers, 2 liver cancers, 3 lung cancers, 7 ovarian cancers, 2 pancreatic cancers, 3 skin cancers, 1 gastric cancer, 1 uterine cancer, Figure 1G) Peptide: IVDDLTINL (A*02) (SEQ ID NO. 8); Tissues arranged from left to right: 1 cell line, 1 colon cancer, 2 esophageal cancers, 2 gallbladder cancers, 5 lung cancers, 1 lymph node cancer, 1 pancreatic cancer, 2 skin cancers, 4 cancers stomach, 1 urinary bladder cancer, 4 uterine cancers, Figure 1H) Peptide: LLAGQTYHV (A*02) (SEQ ID NO. 13); Tissues arranged from left to right: 6 cell lines, 1 lung, 1 placenta, 2 bile duct cancers, 3 breast cancers, 2 colon cancers, 2 esophageal cancers, 2 gallbladder cancers, 1 liver cancer, 36 cancers lung, 3 ovarian cancers, 3 pancreatic cancers, 1 rectal cancer, 3 urinary bladder cancers; and Figure 11) Peptide: VLAKPGVISV (A*02) (SEQ ID NO. 14); Tissues arranged from left to right: 7 cell lines, 1 lung, 1 bile duct cancer, 4 breast cancers, 1 colon cancer, 2 esophageal cancers, 1 gallbladder cancer, 36 lung cancers, 1 ovarian cancer , 3 pancreatic cancers, 2 rectal cancers, 1 gastric cancer, 1 urinary bladder cancer. Figure 2 shows exemplary expression profiles n / ccnn / zznz / Ε / γΐΛΐ 125 (relative expression compared to normal kidney) of genes originating from the present invention that are strongly overexpressed or expressed exclusively in pancreatic cancer in a set of normal tissues (dark gray) and from 11 pancreatic cancer samples ( grey). Figure 2A) LAMC2; Tissues from left to right: 1 adrenal gland, 1 artery, 1 bone marrow, 1 brain (whole), 1 breast, 1 colon, 1 esophagus, 1 heart, 3 kidneys, 1 leukocyte sample, 1 liver, 1 lung, 1 lymph node, 1 ovary, 1 pancreas, 1 placenta, 1 prostate, 1 salivary gland, 1 skeletal muscle, 1 skin, 1 small intestine, 1 spleen, 1 stomach, 1 testicle, 1 thymus, 1 thyroid gland, 1 urinary bladder, 1 cervix, 1 uterus, 1 vein, and 18 pancreas tumors; Figure 2B) VCAN; Tissues from left to right: 1 adrenal gland, 1 artery, 1 bone marrow, 1 brain (whole), 1 breast, 1 colon, 1 esophagus, 1 heart, 3 kidneys, 1 leukocyte sample, 1 liver, 1 lung, 1 lymph node, 1 ovary, 1 pancreas, 1 placenta, 1 prostate, 1 salivary gland, 1 skeletal muscle, 1 skin, 1 small intestine, 1 spleen, 1 stomach, 1 testicle, 1 thymus, 1 thyroid gland, 1 urinary bladder, 1 cervix, 1 uterus, 1 vein, and 18 pancreas tumors; Figure 2C) FAP; Tissues from left to right: 1 adrenal gland, 1 artery, 1 bone marrow, 1 brain (whole), 1 breast, 1 colon, 1 esophagus, 1 heart, 3 kidneys, 1 leukocyte sample, 1 liver, 1 lung, 1 lymph node, 1 ovary, 1 pancreas, 1 placenta, 1 prostate, 1 salivary gland, 1 skeletal muscle, 1 skin, 1 small intestine, 1 spleen, 1 stomach, 1 testicle, 1 thymus, 1 thyroid gland, 1 urinary bladder, 1 cervix, 1 uterus, 1 vein, and 18 pancreas tumors; Figure 3 shows exemplary immunogenicity data: flow cytometry results after staining with peptide-specific multimers. Figure 3 (C and D) shows exemplary results of peptide-specific CD8+ T cell responses from a healthy HLA-A*02+ donor obtained under in vitro conditions. CD8+ T cells were n / ccnn / zznz / E / YiAi 126 sensitized with artificial APCs covered with anti-CD28 mAb and HLAA*02 forming a complex with the peptide of SEQ ID NO. 3 (C, left box) or the peptide of SEQ ID NO. 50 (D, left panel), respectively. After three cycles of stimulation, cells that reacted to the peptide were detected by 2D staining of the multimers with A*02 / SEQ ID NO. 3 (C) or A*02 / SEC ID NO. 50 (D). The right insets (C and D) show control staining of cells stimulated with A*02 / irrelevant peptide complexes. CD8+ lymphocytes were selected from single cells (singlets). With Boolean selections, false positives detected with specific multimers of different peptides could be excluded. The frequencies of specific multimer+ cells among CD8+ lymphocytes are indicated. n / ccnn / zznz / E / YiAi Examples Example 1: Identification and quantification of tumor-associated peptides presented on the cell surface Fabric samples Patients' tumor tissues were obtained from Asterand (Detroit, USA and Royston, Herts, UK); Geneticist Inc. (Glendale, California, USA); Heidelberg Hospital; Tübingen University Hospital. Normal tissues were obtained from BioOptions Inc. (California, USA); BioServe (Beltsville, Maryland, USA); Capital BioScience Inc. (Rockville, Maryland, USA); Geneticist Inc. (Glendale, California, USA); Geneva University Hospital; Heidelberg University Hospital; Kyoto Prefectural University of Medicine (KPUM); Munich University Hospital; ProteoGenex Inc. (Culver City, California, USA); Tübingen University Hospital. Patients provided written informed consent before surgery or autopsy. Tissues were cryogenic in liquid nitrogen immediately after excision and remained at -70SC until isolation of TUMAPs. 127 Isolation of HLA peptides from tissue samples HLA peptide pools from cryogenic tissue samples were obtained by immunoprecipitation from solid tissues following a slightly modified protocol (Falk et al., Nature 351 (1991): 290-296; Seeger et al., Immunogenetics 49 (1999). : 571-576) with the HLA-A*02 specific antibody BB7.2, the HLA-A, B and C specific antibody W6 / 32, CNBr-activated sepharose, acid treatment and u 11 raf i 11 rae i or n. Analysis by mass spectrometry HLA peptide mixtures were separated based on their hydrophobicity with reversed-phase chromatography (nanoAcquity UPLC system, Waters) and the eluted peptides were analyzed with an LTQ-Orbitrap hybrid mass spectrometer (ThermoElectron) equipped with an ESI source. Peptide mixtures were loaded directly onto a fused silica microcapillary column (75 pm i.d. x 250 mm) packed with 1.7 pm C18 reversed phase material (Waters) applying a flow rate of 400 ni per minute. Subsequently, the peptides were separated with a binary gradient of 180 minutes in two phases with 10% to 33% B with a flow rate of 300 ni per minute. The gradient was composed of solvent A (0.1% formic acid in water) and solvent B (0.1% formic acid in acetonitrile). For introduction into the nano-ESI source, a gold-coated glass capillary (PicoTip, New Objective) was used. The LTQ-Orbitrap mass spectrometers were operated in data-dependent mode with the TOP5 method. Briefly, a scan cycle was started with a full high-mass precision scan on the orbitrap (R = 30,000), followed by MS / MS scans also on the orbitrap (R = 7,500) with the top 5 precursor ions. abundant and dynamic exclusion of preselected ions. Tandem mass spectra were interpreted with SEQUEST and additional manual control. The identified peptide sequence was confirmed by comparing the fragmentation pattern generated by the natural peptide with the fragmentation pattern of a synthetic reference peptide of identical sequence. n / ccnn / zznz / E / YiAi 128 The relative quantification of label-free LC-MS was carried out by ion counting, that is, by extraction and analysis of LC-MS characteristics (Mueller et al., 2007). The method assumes that the LC-MS signal areas EM of a peptide are correlated with its abundance in the sample. The extracted features were further processed with charge state deconvolution and retention time alignment (Mueller et al., 2008; Sturm et al., 2008). Finally, all LC-MS features were cross-checked with the sequence identification results to combine the quantitative data from different samples and tissues with the peptide presentation profiles. The quantitative data were two-thirds normalized according to the central tendency to account for variation between technical and biological duplicates. Thus, each identified peptide can be associated with quantitative data that allows relative quantification between samples and tissues. Furthermore, all acquired quantitative data of the peptide candidates were manually reviewed to check data consistency and verify the accuracy of the automated analysis. A presentation profile was calculated for each peptide showing the average presentation of the sample as well as the variations of the duplicates. The profile overlays pancreatic cancer samples with reference normal tissue samples. Presentation profiles of overrepresented peptides are shown in Figure 2 as an example. The presentation scores of the exemplary peptides are shown in Table 8. Table 8: Degrees of presentation. The table lists the peptides that are overpresented to varying degrees in tumors compared to a group of normal tissues: Very highly overpresented in tumors compared to normal tissues (++ +); highly overpresented in tumors compared to normal tissues (++); overpresented in tumors compared to normal tissues (+). n / ccnn / zznz / Ε / γΐΛΐ SEQ ID NO. Sequence Presentation of peptide 1 FLAQQESEI +++ 129 2 SLQEEHVAVA ++ 3 ALLTFMEQV +++ 4 SVDVSPPKV + 5 LLVDDSFLHTV +++ 7 AQQESEIAGI +++ 8 IVDDLTINL +++ 9 FLFDGSANLV +++ 10 FLVDGSSAL +++ 11 FLYKIIDEL +++ 12 FVSEIVDTV +++ 13 LLAGQTYHV + + 14 VLAKPGVISV + 15 SLANNVTSV + 16 APVNVTTEVKSV +++ 17 FLKSGDAAIV +++ 18 SLLDDELMSL ++ 19 HLAPETDEDDL +++ 20 RLAGDGVGAV ++ 21 HLMDQPLSV +++ 23 SLSAFTLFL + 24 GLLEELVTV +++ 25 SLKEEVGEEA I + 26 SLKEEVGEEAIV ++ 29 FLQEYLDAI +++ 31 SLAAAAGKQEL +++ 32 SLAAAAGKQELA +++ 33 SLDSRLELA +++ 34 MLMPVHFLL +++ 35 VMDSGDGVTHTV + 36 KQEYDESGPSIVH +++ 37 GLLKKINSV +++ 38 NLVEKTPALV +++ 39 TLLSNLEEA + 40 FILDSAETTT L++ + n / ccnn / zznz / Ε / γΐΛΐ 130 41 FLLDGSEGV +++ 42 KLVDKSTEL +++ 43 RLDQRVPQI ++ 46 TFAPVNVTTEVKSV + 47 KMDASLGNLFA +++ 48 ALTQTGGPHV +++ 49 NLKGTFATL +++ 50 ALAAILTRL +++ 51 ALMLQGVDL +++ 52 RMVEEIGVEL ++ 56 GLLDYATGAIG SV++ + 57 FLGKVVIDV +++ 58 GLAAFKAFL +++ 59 KLFNLSKEDDV +++ 61 ALEKDYEEVGV +++ 62 ALEKDYEEV +++ 63 FAGDDAPR +++ 64 FLVSNMLLAEA +++ 66 ALLSGLREA +++ 67 KMFFLIDKV +++ 68 KLLTEVHAA ++ + 70 FLVDGSWSV +++ 71 FLLDGSANV +++ 74 KIQEILTQV +++ 75 RLDDLKMTV ++ 76 RLLDSVSRL + 77 GLTDNIHLV +++ 79 VLAPRVLRA + 80 TLYPHTSQV + 81 AMSSKFFLV +++ 82 SISDVIAQV +++ 83 FLIDSSEGV +++ 84 NLLDLDYEL +++ 131 85 TVAEVIQSV ++ 86 SLLAQNTSWLL ++ 87 LLLGSPAAA +++ n / ccnn / zznz / Ε / γΐΛΐ Example 2. Expression profile of the genes that encode the peptides of the invention The overpresentation or specific presentation of a peptide in tumor cells with respect to normal cells is sufficient for it to be useful in immunotherapy, and some peptides are tumor specific even though the protein from which they come is also present in the tissues. normal. Furthermore, obtaining mRNA expression profiles adds another level of security to the selection of peptide targets for immunotherapy. Specifically for therapeutic options subject to a high safety risk, such as affinity-matured TCRs, the ideal target peptide will be one derived from a protein that is exclusive to the tumor and is not found in normal tissues. RNA sources and preparation The excised tissue samples were provided by various institutions (see Example 1); All patients provided written informed consent. Tumor tissue samples were snap frozen in liquid nitrogen immediately postoperatively and homogenized by hand in a mortar and pestle with liquid nitrogen. Total RNA was prepared from these samples with TRI Reagent (Ambion, Darmstadt, Germany) and then purified with RNeasy (QIAGEN, Hilden, Germany); Both methods were carried out following the manufacturer's instructions. Total RNA from healthy human tissues was obtained through commercial channels (Ambion, Huntingdon, UK; Clontech, Heidelberg, Germany; Stratagene, Amsterdam, Netherlands; BioChain, Hayward, California, USA). The RNA from several individuals (from 2 to 123 individuals) was mixed in such a way that the RNA from each of them was represented in the same proportion. 132 The quality and quantity of the RNA samples was assessed with the Agilent 2100 Bioanalyzer (Agilent, Waldbronn, Germany) and the RNA 6000 Pico LabChip Kit (Agilent). Microarray experiments Gene expression analysis of all RNA samples from tumor and normal tissue was performed with Affymetrix Human Genome (HG) LJ133A or HG-U133 Plus 2.0 oligonucleotide microarrays (Affymetrix, Santa Clara, California, USA). . All steps were carried out following the Affymetrix manual. In summary, double-stranded cDNA was synthesized from 5-8 pg of total RNA with SuperScript RTII (Invitrogen) and the oligo-dT-T7 primer (MWG Biotech, Ebersberg, Germany) following the instructions in the manual. In vitro transcription was carried out with the BioArray High Yield RNA Transcript Labeling Kit (ENZO Diagnostics, Inc., Farmingdale, NY, USA) in the case of U133A arrays and with the GeneChip IVT Labeling Kit (Affymetrix) in the U133 Plus 2.0 matrices, and then the cRNA was fragmented, hybridized and stained with streptavidin-phycoerythrin and a biotinylated anti-streptavidin antibody (Molecular Probes, Leiden, Netherlands). Images were analyzed with the Agilent 2500A GeneArray Scanner (U133A) or the Affymetrix GeneChip Scanner 3000 (U133 Plus 2.0), and the data were analyzed with GCOS software (Affymetrix), applying pre-programmed settings to all parameters. For normalization, 100 housekeeping genes supplied by Affymetrix were used. Relative expression values ​​were calculated from the log signal ratios given by the software and the normal kidney sample was arbitrarily set to 1.0. Figure 1 shows examples of expression profiles of genes originating from the present invention that are highly overexpressed or that are expressed exclusively in pancreatic cancer. The expression levels of other genes shown by way of example are set out in Table 9. Table 9: Degrees of expression. The table lists the peptides derived from genes that are very highly overpresented in tumors compared to tissues n / ccnn / zznz / Ε / γΐΛΐ 133 normal (+++); highly overpresented in tumors in normal tissues (++); overrepresented compared to normal tissues (+). comparison tumors in n / ccnn / zznz / Ε / γΐΛΐ SEQ ID NO. Sequence Gene expression 3 ALLTFMEQV ++ 4 SVDVSPPKV + 6 VLISLKQAPLV + 13 LLAGQTYHV + 15 SLANNVTSV + 16 APVNVTTEVKSV + 20 RLAGDGVGAV + 23 SLSAFTLFL + 25 SLKEEVGEEAI ++ 27 YLQGQRLDNV + 30 VVDEGPTG V ++ 36 KQEYDESGPSIVH + 43 RLDQRVPQI + 44 VLLDKIKNLQV + 46 TFAPVNVTTEVKSV ++ 47 KMDASLGNLFA + 48 ALTQTGGPHV + 50 ALAAILTRL +++ 51 ALMLQGVDL ++ 52 RMVEEIGVEL + 57 FLGKVVIDV + 58 GLAAFKAFL + 59 KLFNLSKEDDV + 61 ALEKDYEEVGV +++ 62 ALEKDYEEV +++ 66 ALLSGLREA ++ 67 KMFFLIDKV + 71 FLLDGSANV + 73 TLVAIVVGV++ 134 75 RLDDLKMTV ++ 76 RLLDSVSRL +++ 78 TLSSIKVEV +++ 81 AMSSKFFLV ++ n / ccnn / zznz / E / YiAi Example 3. In vitro immunogenicity of peptides presented by MHC class I In order to gather information on the immunogenicity of the TUMAPs of the present invention, the inventors carried out studies with an in vitro T cell priming assay based on repeated stimulations of CD8+ T cells with loaded artificial antigen presenting cells (aAPCs). with peptide / MHC complexes and anti-CD28 antibody. In this way, the inventors have so far been able to demonstrate the immunogenicity of 22 TUMAPs restricted to HLA-A*0201 of the invention, which demonstrates that these peptides are epitopes of T lymphocytes against which CD8+ precursor T lymphocytes exist in humans (Table 10). In vitro sensitization of CD8 + T lymphocytes To carry out in vitro stimulations with artificial antigen-presenting cells loaded with peptideMHC complex (pMHC) and anti-CD28 antibody, the inventors first isolated CD8+ T lymphocytes from HLA-A*02 leukapheresis products by positive selection with CD8 microbeads ( Miltenyi Biotec, Bergisch-Gladbach, Germany) from healthy donors obtained from the University Clinic of Mannheim, Germany, after informed consent. The isolated CD8+ lymphocytes or PBMC were incubated until use in T cell medium (TCM) consisting of RPMIGlutamax (Invitrogen, Karlsruhe, Germany) supplemented with 10% heat-inactivated human AB serum (PAN-Biotech, Aidenbach, Germany), penicillin 100 U / ml / streptomycin 100 pg / ml (Cambrex, Cologne, Germany), sodium pyruvate 1 mM (CC Pro, Oberdorla, Germany), gentamicin 20 pg / ml (Cambrex). In this step, 2.5 ng / ml IL-7 was also added to the TCM medium (PromoCell, Heidelberg, 135 Germany) and IL-2 10 U / ml (Novartis Pharma, Nuremberg, Germany). The preparation of the pMHC / anti-CD28-coated microbeads, the T cell stimulations and the readout were carried out in a very defined in vitro system with four different pMHC molecules in each stimulation condition and 8 different pMHC molecules in each reading condition. The purified costimulatory antibody Ab 9.3, a mouse IgG2a anti-human CD28 (Jung et al., 1987), was chemically biotinylated with sulfo-N-hydroxysuccinimidobiotin following the manufacturer's recommendations (Perbio, Bonn, Germany). The microbeads used consisted of 5.6 pm diameter polystyrene particles coated with streptavidin (Bangs Laboratories, Illinois, USA). The pMHCs used in the positive and negative control stimulations were A*0201 / MLA-001 (modified Melan-A / MART-1 peptide ELAGIGILTV (SEQ ID NO. 88)) and A*0201 / DDX5-001 (YLLPAIVHI DDX5, SEQ ID NO. 88), respectively. 96-well plates were coated with 800,000 microbeads / 200 μΙ in the presence of 4 x 12.5 ng of different biotinylated pMHC, washed, and then 600 ng of biotinylated anti-CD28 was added in a volume of 200 μΙ. Stimulations were initiated in 96-well plates in which 1x106CD8+ T cells were simultaneously incubated with 2x105coated and washed microbeads in 200 μΙ TCM supplemented with 5 ng / ml IL-12 (PromoCell) for 3 days at 37°C. Half of the medium was renewed with fresh TCM supplemented with 80 U / ml IL-2 and incubation continued for another 4 days at 37°C. This stimulation cycle was carried out a total of three times. To read the pMHC multimers with 8 different pMHC molecules per condition, a two-dimensional combinatorial coding strategy was used as described elsewhere (Andersen et al., 2012), with small modifications involving coupling with 5 different fluorochromes. Finally, multimer analyzes were carried out by staining the cells with the near-IR vital dye Live / dead® (Invitrogen, Karlsruhe, Germany), with anti-CD8-FITC antibody clone SK1 (BD, Heidelberg, Germany). and fluorescent pMHC multimers. For the analysis, a BD LSRII SORP cytometer was equipped with the appropriate filters and lasers. n / ccnn / zznz / E / YiAi cells 136 peptide-specific cells were calculated as a percentage of total CD8 + T lymphocytes. Evaluation of multimeric analysis was performed with FlowJo software (Tree Star, Oregon, USA). In vitro sensitization of specific CD8+ multimer+ lymphocytes was detected by comparing the results with the negative control stimulations. Immunogenicity for a given antigen was confirmed if at least one evaluable in vitro-stimulated well from a healthy donor contained a specific CD8+ T cell line after in vitro stimulation (i.e., the well contained at least 1% multimer+ specificity among CD8+ T cells and the percentage of specific multimer+ cells was at least 10x the median of the negative control stimulations). In vitro immunogenicity of pancreatic cancer peptides In the case of the HLA class I peptides analyzed, in vitro immunogenicity can be demonstrated with the generation of T lymphocyte lines specific for that peptide. Figure 3 shows as an example the results of flow cytometry of three peptides of the invention after staining of specific TUMAP multimers together with that of the corresponding negative controls. The results for 2 peptides of the invention are summarized in Table 10. Table 10: In vitro immunogenicity of HLA class I peptides of the invention Exemplary results of the in vitro immunogenicity experiments carried out by the applicant of the peptides of the invention. <20% = +; 20% - 49% = ++; 50% - 69%= +++; >= 70% = + + + + n / ccnn / zznz / Ε / γΐΛΐ SEQ ID Donor Wells 69 ++ ++++ 87 + +++ 137 The results for another 7 peptides of the invention are summarized in Table 10B. Table 10B: In vitro immunogenicity of HLA class I peptides of the invention. Exemplary results of the in vitro immunogenicity experiments carried out by the applicant of the peptides of the invention. <20% = +; 20% - 49% = ++; 50% - 69%= + + + ; >= 70% = + + + + n / ccnn / zznz / E / YiAi SEQ ID NO. Sequence Positive wells [%] 3 ALLTFMEQV +4- 20 RLAGDGVGAV ++++ 21 HLMDQPLSV + 23 SLSAFTLFL +4- 34 MLMPVHFLL + 37 GLLKKINSV + 50 ALAAILTRL +++ Example 4. Peptide synthesis All peptides were synthesized by standard solid-phase synthesis with the Fmoc strategy. The identity and purity of each peptide was determined with mass spectrometry and analytical RP-HPLC. The peptides were obtained in the form of white or off-white lyophilized (trifluoro salt) with a purity greater than 50%. All TUMAPs were preferably administered as trifluoroacetate or acetate salts, although other types of salts are also feasible. Example 5. MHC binding assays Candidate peptides for T cell treatments according to the present invention were subjected to further analysis to determine their MHC binding capacity (affinity). The different peptide-MHC complexes were produced with UV ligand exchange, a technique in which a UV-sensitive peptide is cleaved 138 after exposing it to said radiation and is exchanged for the peptide of interest that is intended to be analyzed. Only peptide candidates that can bind and stabilize peptide receptor MHC molecules prevent dissociation of MHC complexes. To determine the performance of the exchange reaction, an ELISA was carried out based on the detection of the light chain (p2m) of the stabilized MHC complexes. The test was carried out following the general description of Rodenko and collaborators (Rodenko et al., 2006). MAXISorp 96-well plates (NUNC) were incubated overnight with 2 pg / ml streptavidin in PBS at room temperature, washed 4 times, and blocked for 1 hour at 37°C with blocking buffer containing 2% BSA. . Refolded HLA-A*0201 / MLA-001 monomers were used as standards, in the range of 15 to n / ccnn / zznz / Ε / γΐΛΐ. 500 ng / ml. The peptide-MHC monomers resulting from the UV exchange reaction were diluted 1:100 with blocking buffer. Samples were incubated for 1 h at 37 °C, washed four times, incubated with 2 pg / ml HRP-conjugated anti-p2m antibody for 1 h at 37 °C, washed again, and revealed with TMB solution that was stopped with NH2SO4. The absorption was measured at 450 nm. Candidate peptides exhibiting a high exchange yield (preferably greater than 50% and more preferably greater than 75%) are generally preferred for the generation and production of antibodies or fragments thereof, and / or T cell receptors. or functional fragments thereof, since they show sufficient avidity towards MHC molecules and prevent the dissociation of MHC complexes. Table 11: Percentages of binding to MHC class I. <20% = +; 20% - 49% = ++; 50% - 75%= + + +; >= 75% = + + + + SEQ ID NO. Sequence Peptide change 1 FLAQQESEI ++ 2 SLQEEHVAVA ++ 3 ALLTFMEQV +++ 4 SVDVSPPKV ++ 139 5 LLVDDSFLHTV +++ 6 VLISLKQAPLV ++ 7 AQQESEIAGI ++ 8 IVDDLTINL ++ 9 FLFDGSANLV ++ 10 FLVDGSSAL ++ 11 FLYKIIDEL +++ 12 FVSEIVDTV +++ 13 LLAGQTYHV ++ n / ccnn / zznz / Ε / γΐΛΐ 14 VLAKPGVISV ++ 15 SLANNVTSV ++ 16 APVNVTTEVKSV ++ 17 FLKSGDAAIV ++ 18 SLLDDELMSL ++ 20 RLAGDGVGAV ++ 21 HLMDQPLSV ++ 22 TLDGAAVNQV ++ 23 SLSAFTLFL ++ 24 GLLEELVTV ++ 25 SLKEEV GEEAI ++ 26 SLKEEVGEEAIV ++ 27 YLQGQRLDNV ++ 28 YLQGQRLDNVV ++ 29 FLQEYLDAI +++ 30 VVDEGPTGV ++ 31 SLAAAAGKQEL ++ 32 SLAAAAGKQELA + 33 SLDRLELA ++ 34 MLMPVHFLL ++++ 35 VMDSGDGVTHTV ++ 37 GLLKKINSV ++ 38 NLVEKTPALV +++ 39 TLL SNLEEA++ 140 40 FILDSAETTTL ++ 41 FLLDGSEGV +++ 42 KLVDKSTEL ++ 43 RLDQRVPQI ++ 44 VLLDKIKNLQV ++ 46 TFAPVNVTTEVKSV ++ 47 KMDASLGNLFA ++++ 48 ALTQTGGPHV ++ 49 NLKGTFATL + 50 ALAAILTRL +++ 51 ALML QGVDL++ n / ccnn / zznz / E / YiAi 52 RMVEEIGVEL ++ 53 SSFGGLGGGSV + 54 VLLSEIEVA ++ 55 YLDAMMNEA ++ 56 GLLDYATGAIGSV +++ 57 FLGKVVIDV ++++ 58 GLAAFKAFL +++ 59 KLFNLSKEDDV ++ 60 YLEEDVYQL ++ 64 FLVSNMLLAEA +++ 65 YLYDSET KNA++66 ALLSGLREA +++ 67 KMFFLIDKV +++ List of bibliographical references Agesen, T. 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Claims

1. A peptide comprising an amino acid sequence selected from the group consisting of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, SEC ID NO. 66 to SEC ID NO. 87, and variant sequences thereof that are at least 88% homologous to SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO. 87, wherein said variants bind to one or more major histocompatibility complex (MHC) molecules and / or induce cross-reactivity of T lymphocytes with said variant peptide; and a pharmaceutically acceptable salt thereof, wherein said peptide is not an entire polypeptide.

2. The peptide according to claim 1, wherein said peptide has the ability to bind to an MHC class I or II molecule, and wherein said peptide, when bound to said MHC, is capable of being recognized by CD4 and / or CD8 T lymphocytes.

3. The peptide or variant thereof according to claim 1 or 2, wherein the amino acid sequence thereof comprises a continuous segment of amino acids according to any of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO.

87.

4. The peptide or a variant thereof according to any one of claims 1 to 3, wherein said peptide or variant thereof has a total length of 8 to 100, preferably 8 to 30, more preferably 8 to 16 amino acids, and even more preferably wherein said peptide consists or consists essentially of an amino acid sequence according to any one of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO. 152 87.

5. The peptide or variant thereof according to any of claims 1 to 4, wherein said peptide is modified and / or includes non-peptide linkages.

6. The peptide or variant thereof according to any of claims 1 to 5, wherein said peptide forms part of a fusion protein, in particular comprising N-terminal amino acids of the invariant chain (l1) associated with the HLA-DR antigen.

7. A nucleic acid, encoding a peptide or variant thereof according to any of claims 1 to 6, optionally linked to a heterologous promoter sequence.

8. An expression vector that expresses the nucleic acid according to claim 7.

9. A recombinant host cell comprising the peptide according to claim 1 to 6, the nucleic acid according to claim 7 or the expression vector according to claim 8, wherein said host cell is preferably an antigen-presenting cell such as a dendritic cell.

10. The peptide or variant thereof according to any of claims 1 to 6, the nucleic acid according to claim 7, the expression vector according to claim 8 or the host cell according to claim 9 for use in medicine.

11. A method for producing the peptide or variant thereof according to any of claims 1 to 6, the method comprising culturing the host cell according to claim 9 having said peptide according to claims 1 to 6, or expressing the nucleic acid according to claim 7 or the expression vector according to claim 8, and isolating the peptide or variant thereof from said host cell or its culture medium.

12. An in vitro method for producing activated T lymphocytes, the method comprising contacting in vitro T lymphocytes with antigen loaded on human MHC class I or II molecules expressed on the surface of a suitable antigen-presenting cell 153 or on an artificial construct that mimics an antigen-presenting cell for a period of time sufficient to activate said T lymphocytes in an antigen-specific manner, wherein said antigen is a peptide according to any one of claims 1 to 4.

13. An activated T lymphocyte, produced by the method according to claim 12, selectively recognizing a cell having a polypeptide comprising a given amino acid sequence in any of claims 1 to 4.

14. A method for destroying target cells in a patient whose target cells possess a polypeptide comprising a given amino acid sequence in any of claims 1 to 4, the method comprising administering to the patient an effective number of activated T lymphocytes according to claim 13.

15. An antibody, in particular a soluble or membrane-bound antibody, specifically recognizing the peptide or variant thereof according to any of claims 1 to 5, preferably the peptide or variant thereof according to any of claims 1 to 5 when bound to an MHC molecule.

16. A use of a peptide according to any of claims 1 to 6, of the nucleic acid according to claim 7, of the expression vector according to claim 8, of the cell according to claim 9, of the activated T lymphocyte according to claim 13 or of the antibody according to claim 15, for the treatment of cancer or for the manufacture of a cancer drug.

17. Use according to claim 16, wherein said cancer is selected from the group consisting of: pancreatic cancer, lung cancer, kidney cancer, brain cancer, colorectal or rectal cancer, esophageal cancer, breast cancer, ovarian cancer, gastric cancer, liver cancer, prostate cancer, melanoma, leukemias, and other tumors exhibiting overexpression of a protein from which a peptide is derived according to any of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO.

87.

18. A kit comprising: (a) A container comprising a pharmaceutical composition containing the peptide(s) or variant(s) according to any of claims 1 to 6, the nucleic acid(s) according to claim 7, the expression vector(s) according to claim 8, the cell(s) according to claim 10, the activated T lymphocyte(s) according to claim 13, or the antibody according to claim 15, in solution or in lyophilized form; (b) optionally, a second container containing a diluent or reconstitution solution for the lyophilized formulation; (c) optionally, at least one further peptide selected from the group consisting of SEC ID NO. 1 to 87; and (d) optionally, (I) instructions for use of the solution or (II) for reconstitution and / or use of the lyophilized formulation.

19. The equipment according to claim 18, further comprising one or more of the following components: (III) a buffer, (IV) a diluent, (V) a filter, (VI) a needle, or (V) a syringe.

20. The apparatus according to claim 18 or 19, wherein said peptide is selected from the group consisting of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO.

87.

21. A method for producing a personalized cancer vaccine for a specific patient, wherein said method comprises: (a) identifying tumor-associated peptides (TUMAPs) present in a tumor sample from the patient in question; (b) comparing the peptides identified in step a) with a file or database of peptides that have been preselected for their immunogenicity and / or their overrepresentation in tumors compared to normal tissues; (c) selecting at least one peptide from the file that matches the TUMAP identified in the patient; and (d) formulating the personalized vaccine based on the peptides selected in step c).

22. The method according to claim 21, wherein said TUMAPs are identified by: (a1) comparing the expression data of the tumor sample with the expression data of a corresponding normal tissue sample of the same tissue type as the tumor sample to identify proteins that are overexpressed or aberrantly expressed in the tumor sample; and (a2) correlating the expression data with the sequences of MHC ligands bound to MHC class I and / or class II molecules in the tumor sample to identify MHC ligands derived from proteins that are overexpressed or aberrantly expressed by the tumor.

23. The method according to claim 21 or 22, wherein the MHC ligand sequences are identified by eluting the bound peptides from the MHC molecules isolated from the tumor sample and sequencing the eluted ligands.

24. The method according to any of claims 21 to 23, wherein the normal tissue corresponding to the tissue type of the tumor sample is obtained from the same patient.

25. The method according to any of claims 21 to 24, wherein the peptides included in the file are identified by the following steps: aa. Performing a whole-genome analysis of messenger ribonucleic acid (mRNA) expression using highly parallel methods, such as obtaining expression profiles by means of microarrays or sequencing, comprising identifying genes that are overexpressed in malignant tissue compared to normal tissue or tissues; ab. Selecting peptides encoded by selectively expressed or overexpressed genes detected as described in step aa; and ac. Determining the induction of in vivo T-cell responses by the selected peptides, comprising in vitro immunogenicity assays with human T cells n / ccnn / zznz / E / γΐΛΐ 156 from healthy donors or from said patient; or ba.Identification of HLA ligands from said tumor material by mass spectrometry; bb. Execution of a whole-genome analysis of messenger ribonucleic acid (mRNA) expression using highly parallel methods, such as obtaining expression profiles by means of microarrays or sequencing, which includes the identification of genes that are overexpressed in the malignant tissue compared to normal tissue(s); be. Comparison of the identified HLA ligands with said gene expression data; bd. Selection of the peptides encoded by the selectively expressed or overexpressed genes detected in step be; be. Re-detection of the selected TUMAPs from step bd in the tumor tissue and verification that they are not detected or are infrequently detected in healthy tissues, and confirmation of the relevance of overexpression at the mRNA level; and bf.Determination of the induction of T lymphocyte responses in vivo by the selected peptides, which includes in vitro immunogenicity assays with human T lymphocytes from healthy donors or from said patient.

26. The method according to any of claims 21 to 25, wherein the immunogenicity of the peptides included in the file is determined by a method comprising in vitro immunogenicity assays, immunomonitoring of the patient to determine individual HLA binding, staining of MHC multimers, ELISPOT assays and / or intracellular cytokine staining.

27. The method according to any one of claims 21 to 26, wherein said file comprises a plurality of peptides selected from the group consisting of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO.

87.

28. The method according to any of claims 21 to 27, further comprising identifying at least one mutation that is unique to the tumor sample with respect to the corresponding normal tissue of the patient in question, and selecting a peptide that correlates with the mutation for inclusion in the vaccine or for the creation of cell therapies.

29. The method according to claim 28, wherein at least one such mutation is identified by means of whole genome sequencing.

30. A T-cell receptor, preferably soluble or membrane-bound, that is reactive with an HLA ligand, and said ligand having at least 75% identity with an amino acid sequence selected from the group consisting of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO.

87.

31. The T lymphocyte receptor according to claim 30, wherein said amino acid sequence is at least 88% identical to SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO.

87.

32. The T lymphocyte receptor according to claim 30 or 31, wherein said amino acid sequence consists of any of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO.

87.

33. The T lymphocyte receptor according to any of claims 30 to 32, wherein said T lymphocyte receptor is provided as a soluble molecule and is optionally endowed with another effector function such as an immunostimulatory domain or a toxin.

34. A nucleic acid, encoding a TCR according to any of claims 30 to 33, optionally linked to a heterologous promoter sequence.

35. An expression vector capable of expressing the nucleic acid according to claim 34.

36. A host cell comprising the nucleic acid according to claim 34 or the nucleic acid encoding an antibody according to claim 15 or the expression vector according to claim 35, wherein said host cell n / ccnn / zznz / E / γΐΛΐ 158 is preferably a T lymphocyte or an NK cell.

37. A method for producing the T lymphocyte receptor according to any of claims 30 to 33, the method comprising culturing a host cell according to claim 36, and isolating said T lymphocyte receptor from said host cell and / or its culture medium.

38. A pharmaceutical composition comprising at least one active ingredient selected from the group consisting of: a) a peptide selected from the group consisting of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO. 87; b) a T-cell receptor reactive with a peptide and / or with the peptide-MHC complex according to a); c) a fusion protein comprising a peptide according to (a), and N-terminal amino acids 1 to 80 of the HLA-DR antigen-associated invariant chain (1i);d) nucleic acid encoding any of a) ac) or expression vector comprising said nucleic acid, e) host cell comprising the expression vector of d, f) activated T lymphocyte, obtained by a method comprising contacting in vitro T lymphocytes with a peptide according to a) expressed on the surface of a suitable antigen-presenting cell for a period of time sufficient to activate said T lymphocyte in an antigen-specific manner, as well as a method for transferring said activated T lymphocytes to the same patient from whom they are derived or to other patients;g) an antibody, or soluble T-cell receptor, reactive to a peptide and / or the peptide-MHC complex according to a) and / or a cell presenting a peptide according to a), and potentially modified by its fusion with, for example, immunoactivating domains or toxins, h) an aptamer recognizing a peptide selected from the group consisting of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, SEC ID NO. 66 to SEC ID NO. 87 and / or a complex formed by a peptide selected from the group consisting of SEC ID NO. 65, SEC ID NO. 1 to SEC ID NO. 20, SEC ID NO. 23 to SEC ID NO. 64, and SEC ID NO. 66 to SEC ID NO. 87 with an MHC molecule, i) a peptide or conjugated or labeled support in accordance with any of a) ah) and a pharmaceutically acceptable vehicle, and optionally, pharmaceutically acceptable excipients and / or stabilizers.; 39. An aptamer specifically recognizing the peptide or variant thereof according to any of claims 1 to 5, preferably the peptide or variant thereof according to any of claims 1 to 5 that binds to an MHC molecule.