Patent Publication Number: US-11655281-B2

Title: Immunotherapy with B*07 restricted peptides and combination of peptides against cancers and related methods

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 17/472,290, filed 10 Sep. 2021, which is a continuation of U.S. patent application Ser. No. 16/526,114, filed 30 Jul. 2019, which claims priority to U.S. Provisional Application No. 62/717,462, filed 10 Aug. 2018, and U.S. Provisional Application No. 62/712,691, filed 31 Jul. 2018, as well as German Patent Application No. 102018119555.9, filed 10 Aug. 2018, and German Patent Application No. 102018118550.2, filed 31 Jul. 2018. The disclosures of the priority applications are incorporated in their entirety herein by reference. 
     This application is also related to PCT/EP2019/070430, filed 30 Jul. 2019, the content of which is incorporated herein by reference in its entirety. 
    
    
     REFERENCE TO SEQUENCE LISTING SUBMITTED AS A COMPLIANT ASCII TEXT FILE (.txt) 
     Pursuant to the EFS-Web legal framework and 37 C.F.R. § 1.821-825 (see M.P.E.P. § 2442.03(a)), a Sequence Listing in the form of an ASCII-compliant text file (entitled “Substitute_Sequence_Listing_2912919-096010_ST25.txt” created on Dec. 16, 2022, and 78,021 bytes in size) is submitted concurrently with the instant application, and the entire contents of the Sequence Listing are incorporated herein by reference. 
     BACKGROUND 
     Field 
     The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), 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 for eliciting anti-tumor immune responses, or as targets for the development of pharmaceutically/immunologically active compounds and cells. 
     Description of Related Art 
     According to the World Health Organization (WHO), cancer ranged among the four major non-communicable deadly diseases worldwide in 2012. For the same year, colorectal cancer, breast cancer and respiratory tract cancers were listed within the top 10 causes of death in high income countries. 
     In 2012, 14.1 million new cancer cases, 32.6 million patients suffering from cancer (within 5 years of diagnosis) and 8.2 million cancer deaths were estimated worldwide (Bray et al., 2013; Ferlay et al., 2013). 
     Within the groups of brain cancer, leukemia and lung cancer the current invention specifically focuses on glioblastoma (GBM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), non-small cell and small cell lung cancer (NSCLC and SCLC), respectively. 
     GBM is the most common central nervous system malignancy with an age-adjusted incidence rate of 3.19 per 100,000 inhabitants within the United States. GBM has a very poor prognosis with a 1-year survival rate of 35% and a 5-year survival rate lower than 5%. Male gender, older age and ethnicity appear to be risk factors for GBM (Thakkar et al., 2014). 
     CLL is the most common leukemia in the Western world where it comprises about one third of all leukemia. Incidence rates are similar in the US and Europe, and estimated new cases are about 16,000 per year. CLL is more common in Caucasians than in Africans, rarer in Hispanics and Native Americans and seldom in Asians. In people of Asian origin, CLL incidence rates are 3-fold lower than in Caucasians (Gunawardana et al., 2008). The five-year overall survival for patients with CLL is about 79%. 
     AML is the second most common type of leukemia diagnosed in both adults and children. Estimated new cases in the United States are about 21,000 per year. The five-year survival rate of people with AML is approximately 25%. 
     Lung cancer is the most common type of cancer worldwide and the leading cause of death from cancer in many countries. Lung cancer is subdivided into small cell lung cancer and non-small cell lung cancer. NSCLC includes the histological types adenocarcinoma, squamous cell carcinoma and large cell carcinoma and accounts for 85% of all lung cancers in the United States. The incidence of NSCLC is closely correlated with smoking prevalence, including current and former smokers and the five-year survival rate was reported to be 15% (Molina et al., 2008; World Cancer Report, 2014). 
     Considering the severe side-effects and expense associated with treating cancer, there is a need to identify factors that can be used in the treatment of cancer in general and acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer in particular. There is also a need to identify factors representing biomarkers for cancer in general and acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer in particular, leading to better diagnosis of cancer, assessment of prognosis, and prediction of treatment success. 
     Immunotherapy of cancer represents an option of specific targeting of cancer cells while minimizing side effects. Cancer immunotherapy makes use of the existence of tumor associated antigens. 
     The current classification of tumor associated antigens (TAAs) comprises the following major groups: 
     a) Cancer-testis antigens: The first TAAs ever identified that can be recognized by T cells belong to this class, which was originally called cancer-testis (CT) antigens because of the expression of its members in histologically different human tumors and, among normal tissues, only in spermatocytes/spermatogonia of testis and, occasionally, in placenta. Since the cells of testis do not express class I and II HLA molecules, these antigens cannot be recognized by T cells in normal tissues and can therefore be considered as immunologically tumor-specific. Well-known examples for CT antigens are the MAGE family members and NY-ESO-1. 
     b) Differentiation antigens: These TAAs are shared between tumors and the normal tissue from which the tumor arose. Most of the known differentiation antigens are found in melanomas and normal melanocytes. Many of these melanocyte lineage-related proteins are involved in biosynthesis of melanin and are therefore not tumor specific but nevertheless are widely used for cancer immunotherapy. Examples include, but are not limited to, tyrosinase and Melan-A/MART-1 for melanoma or PSA for prostate cancer. 
     c) Over-expressed TAAs: Genes encoding widely expressed TAAs have been detected in histologically different types of tumors as well as in many normal tissues, generally with lower expression levels. It is possible that many of the epitopes processed and potentially presented by normal tissues are below the threshold level for T-cell recognition, while their over-expression in tumor cells can trigger an anticancer response by breaking previously established tolerance. Prominent examples for this class of TAAs are Her-2/neu, survivin, telomerase, or WT1. 
     d) Tumor-specific antigens: These unique TAAs arise from mutations of normal genes (such as β-catenin, CDK4, etc.). Some of these molecular changes are associated with neoplastic transformation and/or progression. Tumor-specific antigens are generally able to induce strong immune responses without bearing the risk for autoimmune reactions against normal tissues. On the other hand, these TAAs are in most cases only relevant to the exact tumor on which they were identified and are usually not shared between many individual tumors. Tumor-specificity (or -association) of a peptide may also arise if the peptide originates from a tumor-(-associated) exon in case of proteins with tumor-specific (-associated) isoforms. 
     e) TAAs arising from abnormal post-translational modifications: Such TAAs may arise from proteins which are neither specific nor overexpressed in tumors but nevertheless become tumor associated by posttranslational processes primarily active in tumors. Examples for this class arise from altered glycosylation patterns leading to novel epitopes in tumors as for MUC1 or events like protein splicing during degradation which may or may not be tumor specific. 
     f) Oncoviral proteins: These TAAs are viral proteins that may play a critical role in the oncogenic process and, because they are foreign (not of human origin), they can evoke a T-cell response. Examples of such proteins are the human papilloma type 16 virus proteins, E6 and E7, which are expressed in cervical carcinoma. 
     T-cell based immunotherapy targets peptide epitopes derived from tumor-associated or tumor-specific proteins, which are presented by molecules of the major histocompatibility complex (MHC). The antigens that are recognized by the tumor specific T lymphocytes, that is, the epitopes thereof, can be molecules derived from all protein classes, such as enzymes, receptors, transcription factors, etc. which are expressed and, as compared to unaltered cells of the same origin, usually up-regulated in cells of the respective tumor. There are two classes of MHC-molecules, MHC class I and MHC class II. MHC class I molecules are composed of an alpha heavy chain and beta-2-microglobulin, MHC class II molecules of an alpha and a beta chain. Their three-dimensional conformation results in a binding groove, which is used for non-covalent interaction with peptides. 
     MHC class I molecules can be found on most nucleated cells. They present peptides that result from proteolytic cleavage of predominantly endogenous proteins, defective ribosomal products (DRIPs) and larger peptides. However, peptides derived from endosomal compartments or exogenous sources are also frequently found on MHC class I molecules. This non-classical way of class I presentation is referred to as cross-presentation in the literature (Brossart and Bevan, 1997; Rock et al., 1990). MHC class II molecules can be found predominantly on professional antigen presenting cells (APCs), and primarily present peptides of exogenous or transmembrane proteins that are taken up by APCs e.g. during endocytosis and are subsequently processed. 
     Complexes of peptide and MHC class I are recognized by CD8-positive T cells bearing the appropriate T-cell receptor (TCR), whereas complexes of peptide and MHC class II molecules are recognized by CD4-positive-helper-T cells bearing the appropriate TCR. It is well known that the TCR, the peptide and the MHC are thereby present in a stoichiometric amount of 1:1:1. 
     CD4-positive helper T cells play a key role in inducing and sustaining effective responses by CD8-positive cytotoxic T cells. The identification of CD4-positive T-cell epitopes derived from tumor associated antigens (TAA) is of great importance for the development of pharmaceutical products for triggering anti-tumor immune responses (Gnjatic et al., 2003). At the tumor site, T helper cells, support a cytotoxic T cell-(CTL-) friendly cytokine milieu (Mortara et al., 2006) and attract effector cells, e.g. CTLs, natural killer (NK) cells, macrophages, and granulocytes (Hwang et al., 2007). 
     In the absence of inflammation, expression of MHC class II molecules is mainly restricted to cells of the immune system, especially professional antigen-presenting cells (APC), e.g., monocytes, monocyte-derived cells, macrophages, dendritic cells. In cancer patients, cells of the tumor have been found to express MHC class II molecules (Dengjel et al., 2006). 
     Longer (elongated) peptides of the invention can act as MHC class II active epitopes. 
     T-helper cells, activated by MHC class II epitopes, play a key role in orchestrating the effector function of CTLs in anti-tumor immunity. T-helper cell epitopes that trigger a T-helper cell response of the TH1 type support effector functions of CD8-positive killer T cells, which include cytotoxic functions directed against tumor cells displaying tumor-associated peptide/MHC complexes on their cell surfaces. In this way tumor-associated T-helper cell peptide epitopes, alone or in combination with other tumor-associated peptides, can serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. 
     It was shown in mammalian animal models, e.g., mice, that even in the absence of CD8-positive T lymphocytes, CD4-positive T cells are sufficient for inhibiting manifestation of tumors via inhibition of angiogenesis by secretion of interferon-gamma (IFNγ) (Beatty and Paterson, 2001; Mumberg et al., 1999). There is evidence for CD4 T cells as direct anti-tumor effectors (Braumuller et al., 2013; Tran et al., 2014). 
     Since the constitutive expression of HLA class II molecules is usually limited to immune cells, the possibility of isolating class II peptides directly from primary tumors was previously not considered possible. However, Dengjel et al. were successful in identifying a number of MHC Class II epitopes directly from tumors (WO 2007/028574, EP 1 760 088 B1). 
     Since both types of response, CD8 and CD4 dependent, contribute jointly and synergistically to the anti-tumor effect, the identification and characterization of tumor-associated antigens recognized by either CD8+ T cells (ligand: MHC class I molecule+peptide epitope) or by CD4-positive T-helper cells (ligand: MHC class II molecule+peptide epitope) is important in the development of tumor vaccines. 
     For an MHC class I peptide to trigger (elicit) a cellular immune response, it also must bind to an MHC-molecule. This process is dependent on the allele of the MHC-molecule and specific polymorphisms of the amino acid sequence of the peptide. MHC-class-I-binding peptides are usually 8-12 amino acid residues in length and usually contain two conserved residues (“anchors”) in their sequence that interact with the corresponding binding groove of the MHC-molecule. In this way each MHC allele has a “binding motif” determining which peptides can bind specifically to the binding groove. 
     In the MHC class I dependent immune reaction, peptides not only have to be able to bind to certain MHC class I molecules expressed by tumor cells, they subsequently also have to be recognized by T cells bearing specific T cell receptors (TCR). 
     For proteins to be recognized by T-lymphocytes as tumor-specific or -associated antigens, and to be used in a therapy, particular prerequisites must be fulfilled. The antigen should be expressed mainly by tumor cells and not, or in comparably small amounts, by normal healthy tissues. In a preferred embodiment, the peptide should be over-presented by tumor cells as compared to normal healthy tissues. It is furthermore desirable that the respective antigen is not only present in a type of tumor, but also in high concentrations (i.e. copy numbers of the respective peptide per cell). Tumor-specific and tumor-associated antigens are often derived from proteins directly involved in transformation of a normal cell to a tumor cell due to their function, e.g. in cell cycle control or suppression of apoptosis. Additionally, downstream targets of the proteins directly causative for a transformation may be up-regulated and thus may be indirectly tumor-associated. Such indirect tumor-associated antigens may also be targets of a vaccination approach (Singh-Jasuja et al., 2004). It is essential that epitopes are present in the amino acid sequence of the antigen, in order to ensure that such a peptide (“immunogenic peptide”) that is derived from a tumor associated antigen leads to an in vitro or in vivo T-cell-response. 
     Basically, any peptide able to bind an MHC molecule may function as a T-cell epitope. A prerequisite for the induction of an in vitro or in vivo T-cell-response is the presence of a T cell having a corresponding TCR and the absence of immunological tolerance for this particular epitope. 
     Therefore, TAAs are a starting point for the development of a T cell-based therapy including but not limited to tumor vaccines. The methods for identifying and characterizing the TAAs are usually based on the use of T-cells that can be isolated from patients or healthy subjects, or they are based on the generation of differential transcription profiles or differential peptide expression patterns between tumors and normal tissues. However, the identification of genes over-expressed in tumor tissues or human tumor cell lines, or selectively expressed in such tissues or cell lines, does not provide precise information as to the use of the antigens being transcribed from these genes in an immune therapy. This is because only an individual subpopulation of epitopes of these antigens are suitable for such an application since a T cell with a corresponding TCR has to be present and the immunological tolerance for this particular epitope needs to be absent or minimal. In a very preferred embodiment of the invention it is therefore important to select only those over- or selectively presented peptides against which a functional and/or a proliferating T cell can be found. Such a functional T cell is defined as a T cell, which upon stimulation with a specific antigen can be clonally expanded and is able to execute effector functions (“effector T cell”). 
     In case of targeting peptide-MHC by specific TCRs (e.g. soluble TCRs) and antibodies or other binding molecules (scaffolds) according to the invention, the immunogenicity of the underlying peptides is secondary. In these cases, the presentation is the determining factor. 
     SUMMARY 
     In a first aspect of the present invention, the present invention relates to a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499 or a variant sequence 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: 383 and SEQ ID NO: 448 to SEQ ID NO: 499, or a variant sequence comprising one conservative amino acid sequence exchange compared with to SEQ ID NO: 1 through SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499, wherein said variants bind to MHC and/or induces T cells cross-reacting with said peptide, or a pharmaceutical acceptable salt thereof, wherein said peptide is not the underlying full-length polypeptide. 
     The present invention further relates to a peptide of the present invention comprising a sequence that is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499 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: 383 and SEQ ID NO: 448 to SEQ ID NO: 499, wherein said peptide or variant thereof has an overall length of between 8 and 100, preferably between 8 and 30, and most preferred of between 8 and 14 amino acids. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS.  1 A- 1 I  depict embodiments as described herein. 
         FIGS.  1 A through  1 I  show the over-presentation of various peptides in different cancer tissues (black dots). Upper part: Median MS signal intensities from technical replicate measurements are plotted as dots for single HLA-B*07 positive normal (grey dots, left part of figure) and tumor samples (black dots, right part of figure) on which the peptide was detected. Boxes display median, 25th and 75th percentile of normalized signal intensities, while whiskers extend to the lowest data point still within 1.5 interquartile range (IQR) of the lower quartile, and the highest data point still within 1.5 IQR of the upper quartile. Normal organs are ordered according to risk categories (blood cells, blood vessels, brain, liver, lung: high risk, grey dots; all other organs: medium risk; grey dots). Lower part: The relative peptide detection frequency in every organ is shown as spine plot. Numbers below the panel indicate number of samples on which the peptide was detected out of the total number of samples analyzed for each organ (N=87 for normal samples, N=149 for tumor samples). If the peptide has been detected on a sample but could not be quantified for technical reasons, the sample is included in this representation of detection frequency, but no dot is shown in the upper part of the figure. Tissues (from left to right) Normal samples: blood cells; bloodvess (blood vessels); brain; heart; liver, lung; adrenal gl (adrenal gland); bile duct; bladder; bone marrow; esoph (esophagus); gall bl (gallbladder); intest. la (large intestine); intest. sm (small intestine); kidney; lymph node; nerve periph (peripheral nerve); pancreas; pituit (pituitary); skin; spinal cord; spleen; stomach; thyroid; trachea; Tumor samples: AML (acute myeloid leukemia); BRCA (breast cancer); CCC (cholangiocellular carcinoma); CLL (chronic lymphocytic leukemia); CRC (colorectal cancer); GBC (gallbladder cancer); GBM (glioblastoma); GC (gastric cancer); HCC (hepatocellular carcinoma); HNSCC (head and neck squamous cell carcinoma); MEL (melanoma); NHL (non-hodgkin lymphoma); NSCLCadeno (non-small cell lung cancer adenocarcinoma); NSCLCother (NSCLC samples that could not unambiguously be assigned to NSCLCadeno or NSCLCsquam); NSCLCsquam (squamous cell non-small cell lung cancer); OC (ovarian cancer); OSCAR (esophageal cancer); PACA (pancreatic cancer); PRCA (prostate cancer); RCC (renal cell carcinoma); SCLC (small cell lung cancer); UBC (urinary bladder carcinoma); UEC (uterine and endometrial cancer). 
         FIG.  1 A ) Peptide: TPRIGPKVSL (SEQ ID NO.: 206),  FIG.  1 B ) Peptide: RPILKEQSSSSF (SEQ ID NO.: 246),  FIG.  1 C ) Peptide: RPDVVRTLL (SEQ ID NO.: 308),  FIG.  1 D ) Peptide: SPSLQSSRESL (SEQ ID NO.: 312),  FIG.  1 E ) Peptide: NPREPEKSL (SEQ ID NO.: 316),  FIG.  1 F ) Peptide: VPPQNPRPSL (SEQ ID NO.: 335),  FIG.  1 G ) Peptide: IPTSRVITL (SEQ ID NO.: 337),  FIG.  1 H ) Peptide: KPRATWTL (SEQ ID NO.: 353),  FIG.  1 I ) Peptide: SPRRLVELAGQSL (SEQ ID NO.: 359). 
         FIGS.  2 A- 2 T  depict embodiments as described herein. 
         FIGS.  2 A through  2 T  show exemplary expression profile of source genes of the present invention that are over-expressed in different cancer samples. Tumor (black dots) and normal (grey dots) samples are grouped according to organ of origin. Box-and-whisker plots represent median FPKM value, 25th and 75th percentile (box) plus whiskers that extend to the lowest data point still within 1.5 interquartile range (IQR) of the lower quartile and the highest data point still within 1.5 IQR of the upper quartile. Normal organs are ordered according to risk categories. FPKM: fragments per kilobase per million mapped reads. Normal samples: blood cells; bloodvess (blood vessels); brain; heart; liver; lung; adipose (adipose tissue); adrenal gl (adrenal gland); bile duct; bladder; bone marrow; esoph (esophagus); eye; gall bl (gallbladder); head&amp;neck; intest. la (large intestine); intest. sm (small intestine); kidney; lymph node; nerve periph (peripheral nerve); pancreas; parathyr (parathyroid gland); perit (peritoneum); pituit (pituitary); pleura; skel. mus (skeletal muscle); skin; spleen; stomach; thyroid; trachea; ureter; breast; ovary; placenta; prostate; testis; thymus; uterus. Tumor samples: AML (acute myeloid leukemia); BRCA (breast cancer); CCC (cholangiocellular carcinoma); CLL (chronic lymphocytic leukemia); CRC (colorectal cancer); GBC (gallbladder cancer); GBM (glioblastoma); GC (gastric cancer); HCC (hepatocellular carcinoma); HNSCC (head and neck squamous cell carcinoma); MEL (melanoma); NHL (non-hodgkin lymphoma); NSCLCadeno (non-small cell lung cancer adenocarcinoma); NSCLCother (NSCLC samples that could not unambiguously be assigned to NSCLCadeno or NSCLCsquam); NSCLCsquam (squamous cell non-small cell lung cancer); OC (ovarian cancer); OSCAR (esophageal cancer); other (other cancers, e.g. multiple myeloma); PACA (pancreatic cancer); PRCA (prostate cancer); RCC (renal cell carcinoma); SCLC (small cell lung cancer); UBC (urinary bladder carcinoma); UEC (uterine and endometrial cancer). 
         FIG.  2 A ) Gene symbol: KLK2, Peptide: RPRSLQCVSL (SEQ ID No.: 1),  FIG.  2 B ) Gene symbol: TGM4, Peptide: GPKKFIVKL (SEQ ID No.: 4),  FIG.  2 C ) Gene symbol: PRAME, Peptide: LPSLSHCSQL (SEQ ID No.: 5),  FIG.  2 D ) Gene symbol: MMP12, Peptide: AVHEIGHSL (SEQ ID No.: 14),  FIG.  2 E ) Gene symbol: FAM178B, Peptide: WPRLPGAGL (SEQ ID No.: 19),  FIG.  2 F ) Gene symbol: LOC645382/LOC645399/PRAMEF10, Peptide: APSRLLEL (SEQ ID No.: 21),  FIG.  2 G ) Gene symbol: MAGEC1, Peptide: SPSFSSTLLSL (SEQ ID No.: 26),  FIG.  2 H ) Gene symbol: CYP4Z1/CYP4Z2P, Peptide: FPAPPAHWF (SEQ ID No.: 16),  FIG.  2 I ) Gene symbol: UPK2, Peptide: APLLPIRTLPL (SEQ ID No.: 58),  FIG.  2 J ) Gene symbol: ALPPL2, Peptide: DAAHPGPSV (SEQ ID No.: 82),  FIG.  2 K ) Gene symbol: MMP1, Peptide: HAIEKAFQL (SEQ ID No.: 90),  FIG.  2 L ) Gene symbol: COL10A1, Peptide: TPIPFDKILY (SEQ ID No.: 100),  FIG.  2 M ) Gene symbol: LAMC2, Peptide: RSYQHSLRL (SEQ ID No.: 116),  FIG.  2 N ) Gene symbol: LAMC2, Peptide: SPQLSYFEY (SEQ ID No.: 137),  FIG.  2 O ) Gene symbol: SLC45A2, Peptide: VPFNLITEY (SEQ ID No.: 138),  FIG.  2 P ) Gene symbol: QRFPR, Peptide: HPFKMKWQY (SEQ ID No.: 142),  FIG.  2 Q ) Gene symbol: KBTBD8, Peptide: TPMTVPRI (SEQ ID No.: 159),  FIG.  2 R ) Gene symbol: KBTBD8, Peptide: YAYTSRVIL (SEQ ID No.: 166),  FIG.  2 S ) Gene symbol: NLRP2, Peptide: LPKAALLV (SEQ ID No.: 241),  FIG.  2 T ) Gene symbol: DCAF4L2, Peptide: APSMLRKNQL (SEQ ID No.: 358). 
         FIGS.  3 A- 3 G  depict embodiments as described herein. 
         FIGS.  3 A through  3 G  show exemplary results of peptide-specific in vitro CD8+ T cell responses of a healthy HLA-B*07+ donor. CD8+ T cells were primed using artificial APCs coated with anti-CD28 mAb and HLA-B*07 in complex with SEQ ID No.: 388 peptide (SPSVSQLSVL) ( FIG.  3 A , left panel), SEQ ID No.: 406 peptide (LPDGSRVEL) ( FIG.  3 B , left panel), SEQ ID No.: 23 peptide (VPRPTSTVGL) ( FIG.  3 C , left panel), SEQ ID No.: 33 peptide (LPRGLSPARQL) ( FIG.  3 D , left panel), SEQ ID No.: 61 peptide (LPRIPFSTF) ( FIG.  3 E , left panel), SEQ ID No.: 64 peptide (VPRPIFSQLYL) ( FIG.  3 F , left panel), SEQ ID No.: 68 peptide (FPNEVSVVL) ( FIG.  3 G , left panel). After three cycles of stimulation, the detection of peptide-reactive cells was performed by 2D multimer staining with B*07/SEQ ID No.: 388 ( FIG.  3 A ), B*07/SEQ ID No.: 406 ( FIG.  3 B ), B*07/SEQ ID No.: 23 ( FIG.  3 C ), B*07/SEQ ID No.: 33 ( FIG.  3 D ), B*07/SEQ ID No.: 61 ( FIG.  3 E ), B*07/SEQ ID No.: 64 ( FIG.  3 F ) or B*07/SEQ ID No.: 68 ( FIG.  3 G ). Right panel ( FIG.  3 A through  3 G ) show control staining of cells stimulated with irrelevant B*07/peptide complexes. Viable singlet cells were gated for CD8+ lymphocytes. Boolean gates helped excluding false-positive events detected with multimers specific for different peptides. Frequencies of specific multimer+ cells among CD8+ lymphocytes are indicated. 
     
    
    
     DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT 
     The following tables show the peptides according to the present invention, their respective SEQ ID NOs, and the prospective source (underlying) genes for these peptides. In Table 1a, peptides with SEQ ID NO: 1 to SEQ ID NO: 357 bind to HLA-B*07. In Table 1 b, peptides with SEQ ID NO: 448 to SEQ ID NO: 497 bind to HLA-B*07. The peptides in Table 2 have been disclosed before in large listings as results of high-throughput screenings with high error rates or calculated using algorithms but have not been associated with cancer at all before. In Table 2a, peptides with SEQ ID NO: 358 to SEQ ID NO: 383 bind to HLA-B*07. In Table 2b, peptides with SEQ ID NO: 498 to SEQ ID NO 499: bind to HLA-B*07. The peptides in Table 3 are additional peptides that may be useful in combination with the other peptides of the invention. In Table 3, peptides with SEQ ID NO: 384 to SEQ ID NO: 445 bind to HLA-B*07. 
     
       
         
           
               
             
               
                 TABLE 1a 
               
             
            
               
                   
               
               
                 Peptides accordinq to the present invention. 
               
            
           
           
               
               
               
               
            
               
                 Seq 
                   
                   
                   
               
               
                 ID 
                   
                   
                   
               
               
                 No 
                 Sequence 
                 Gene(s) 
                 HLA allotype 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 1 
                 RPRSLQCVSL 
                 KLK2 
                 B*07 
               
               
                   
               
               
                 2 
                 VPGSDPARYEFL 
                 MAGEA10 
                 B*07 
               
               
                   
               
               
                 3 
                 MPYVVLTAL 
                 SLC6A3 
                 B*07 
               
               
                   
               
               
                 4 
                 GPKKFIVKL 
                 TGM4 
                 B*07 
               
               
                   
               
               
                 5 
                 LPSLSHCSQL 
                 PRAME 
                 B*07 
               
               
                   
               
               
                 6 
                 LPLNSSTSL 
                 MMP12 
                 B*07 
               
               
                   
               
               
                 7 
                 RPSQLAPATL 
                 LOC100507003 
                 B*07 
               
               
                   
               
               
                 8 
                 MPKTNLSKM 
                 LOC100507003 
                 B*07 
               
               
                   
               
               
                 9 
                 RPDSRLLEL 
                 CTAG2 
                 B*07 
               
               
                   
               
               
                 10 
                 SPMEAELVRRIL 
                 CTAG2 
                 B*07 
               
               
                   
               
               
                 11 
                 APLPRPGAV 
                 CTAG2 
                 B*07 
               
               
                   
               
               
                 12 
                 LPNTGRIGQLL 
                 TGM4 
                 B*07 
               
               
                   
               
               
                 13 
                 LPNTGRIGQL 
                 TGM4 
                 B*07 
               
               
                   
               
               
                 14 
                 AVHEIGHSL 
                 MMP12 
                 B*07 
               
               
                   
               
               
                 15 
                 KPGFNISIL 
                 CYP4Z1, CYP4Z2P 
                 B*07 
               
               
                   
               
               
                 16 
                 FPAPPAHWF 
                 CYP4Z1, CYP4Z2P 
                 B*07 
               
               
                   
               
               
                 17 
                 SPAAPLSPASSL 
                 CRH 
                 B*07 
               
               
                   
               
               
                 18 
                 MALSVLRLAL 
                 SPINK2 
                 B*07 
               
               
                   
               
               
                 19 
                 WPRLPGAGL 
                 FAM178B 
                 B*07 
               
               
                   
               
               
                 20 
                 MVLGIGPVL 
                 SLC45A3 
                 B*07 
               
               
                   
               
               
                 21 
                 APSRLLEL 
                 LOC645382, LOC645399, PRAMEF10 
                 B*07 
               
               
                   
               
               
                 22 
                 LPQLKPAL 
                 AMTN 
                 B*07 
               
               
                   
               
               
                 23 
                 VPRPTSTVGL 
                 TRIM51, TRIM51BP, TRIM51EP, 
                 B*07 
               
               
                   
                   
                 TRIM51HP 
                   
               
               
                   
               
               
                 24 
                 VPRPTSTVGLFL 
                 TRIM51, TRIM51BP, TRIM51EP, 
                 B*07 
               
               
                   
                   
                 TRIM51HP 
                   
               
               
                   
               
               
                 25 
                 RPQGAVGGL 
                 RHOXF2, RHOXF2B 
                 B*07 
               
               
                   
               
               
                 26 
                 SPSFSSTLLSL 
                 MAGEC1 
                 B*07 
               
               
                   
               
               
                 27 
                 RIRVTSEVL 
                 ABCC11 
                 B*07 
               
               
                   
               
               
                 28 
                 LPAPTSLVL 
                 COL20A1 
                 B*07 
               
               
                   
               
               
                 29 
                 APLRVHITSL 
                 PAEP 
                 B*07 
               
               
                   
               
               
                 30 
                 YPGFTKRL 
                 ACTL8 
                 B*07 
               
               
                   
               
               
                 31 
                 RPGPSDPAA 
                 KISS1R 
                 B*07 
               
               
                   
               
               
                 32 
                 APMAPGRSPL 
                 PGR 
                 B*07 
               
               
                   
               
               
                 33 
                 LPRGLSPARQL 
                 PGR 
                 B*07 
               
               
                   
               
               
                 34 
                 APMAPGRSP 
                 PGR 
                 B*07 
               
               
                   
               
               
                 35 
                 APLPPPRAL 
                 COL20A1 
                 B*07 
               
               
                   
               
               
                 36 
                 RPFSREMDL 
                 FLT3 
                 B*07 
               
               
                   
               
               
                 37 
                 LPPPRALTL 
                 COL20A1 
                 B*07 
               
               
                   
               
               
                 38 
                 RPSFPNLTSF 
                 FLT3 
                 B*07 
               
               
                   
               
               
                 39 
                 QPRPSSEKI 
                 POU4F1, POU4F2, POU4F3 
                 B*07 
               
               
                   
               
               
                 40 
                 FPRTVKHIDAAL 
                 MMP1 
                 B*07 
               
               
                   
               
               
                 41 
                 MPAGGGPRSL 
                 CKAP4 
                 B*07 
               
               
                   
               
               
                 42 
                 APLKMLAL 
                 CCL17 
                 B*07 
               
               
                   
               
               
                 43 
                 APTPRPKVL 
                 BMPR1B 
                 B*07 
               
               
                   
               
               
                 44 
                 SPSQTVQRAV 
                 IGHE 
                 B*07 
               
               
                   
               
               
                 45 
                 TRPWSGPYIL 
                 DCT 
                 B*07 
               
               
                   
               
               
                 46 
                 QPISGNPVTL 
                 FCRL5 
                 B*07 
               
               
                   
               
               
                 47 
                 RPRQTGALM 
                 DNTT 
                 B*07 
               
               
                   
               
               
                 48 
                 RPRYSIGL 
                 BMPR1B 
                 B*07 
               
               
                   
               
               
                 49 
                 APEKARAFL 
                 SOX14 
                 B*07 
               
               
                   
               
               
                 50 
                 PEKARAFL 
                 SOX14 
                 B*07 
               
               
                   
               
               
                 51 
                 SPVFYVQTL 
                 ABCC11 
                 B*07 
               
               
                   
               
               
                 52 
                 KEDNPSGHTYTL 
                 MAGEB1 
                 B*07 
               
               
                   
               
               
                 53 
                 SPRIPFSTF 
                 ROPN1 
                 B*07 
               
               
                   
               
               
                 54 
                 VPSCGRSVEGL 
                 PTHLH 
                 B*07 
               
               
                   
               
               
                 55 
                 LPALLRSGL 
                 RAPGEF5 
                 B*07 
               
               
                   
               
               
                 56 
                 LPALLRSGLTL 
                 RAPGEF5 
                 B*07 
               
               
                   
               
               
                 57 
                 APLLPIRTL 
                 UPK2 
                 B*07 
               
               
                   
               
               
                 58 
                 APLLPIRTLPL 
                 UPK2 
                 B*07 
               
               
                   
               
               
                 59 
                 KPRTIYSSL 
                 DLX1, DLX4, DLX6 
                 B*07 
               
               
                   
               
               
                 60 
                 RPYSIYPHGVTF 
                 F5 
                 B*07 
               
               
                   
               
               
                 61 
                 LPRIPFSTF 
                 ROPN1B 
                 B*07 
               
               
                   
               
               
                 62 
                 KPQSTISGL 
                 F5 
                 B*07 
               
               
                   
               
               
                 63 
                 FPHMATTAF 
                 HEPHL1 
                 B*07 
               
               
                   
               
               
                 64 
                 VPRPIFSQLYL 
                 GREB1, GREB1L 
                 B*07 
               
               
                   
               
               
                 65 
                 FPNVYSTLVL 
                 SLC45A2 
                 B*07 
               
               
                   
               
               
                 66 
                 LPMTVISVL 
                 NMUR2 
                 B*07 
               
               
                   
               
               
                 67 
                 VPVSRPVL 
                 FCRL2, FCRL3, FCRL5 
                 B*07 
               
               
                   
               
               
                 68 
                 FPNEVSVVL 
                 HMCN1 
                 B*07 
               
               
                   
               
               
                 69 
                 RPEDGRPRL 
                 BTBD17 
                 B*07 
               
               
                   
               
               
                 70 
                 VPAQRLGLL 
                 IGKV1D-43 
                 B*07 
               
               
                   
               
               
                 71 
                 APFAPLHGGGSL 
                 NEFH 
                 B*07 
               
               
                   
               
               
                 72 
                 APCNGNVAV 
                 KRT81 
                 B*07 
               
               
                   
               
               
                 73 
                 LPVSSPVTL 
                 AKNAD1 
                 B*07 
               
               
                   
               
               
                 74 
                 VPVSHPVL 
                 FCRL3, FCRL5 
                 B*07 
               
               
                   
               
               
                 75 
                 HVRPQTNCI 
                 DCC 
                 B*07 
               
               
                   
               
               
                 76 
                 KPKVESQAL 
                 ABCC11 
                 B*07 
               
               
                   
               
               
                 77 
                 QPRLVPGETL 
                 FMN1, LOC101059984 
                 B*07 
               
               
                   
               
               
                 78 
                 HPSQESPTL 
                 DLX5 
                 B*07 
               
               
                   
               
               
                 79 
                 GPASDHPSL 
                 GREB1 
                 B*07 
               
               
                   
               
               
                 80 
                 SALPTTISF 
                 MAGEA4 
                 B*07/B*35 
               
               
                   
               
               
                 81 
                 IAYPSLREAAL 
                 MAGEA4 
                 B*07/C*03 
               
               
                   
               
               
                 82 
                 DAAHPGPSV 
                 ALPPL2 
                 B*07/B*51 
               
               
                   
               
               
                 83 
                 AVSSHHNVI 
                 POTEG 
                 B*07 
               
               
                   
               
               
                 84 
                 MPMQDIKMI 
                 PRAME 
                 B*07/B*51 
               
               
                   
               
               
                 85 
                 MPMQDIKMILKM 
                 PRAME 
                 B*07/B*35 
               
               
                   
               
               
                 86 
                 ALLLRGVTL 
                 SLC6A3 
                 B*07/C*06 
               
               
                   
               
               
                 87 
                 APVGGNVTSSF 
                 CT45A1, CT45A2, CT45A3, CT45A4, 
                 B*07/B*35 
               
               
                   
                   
                 CT45A6, LOC101060208, LOC101060210, 
                   
               
               
                   
                   
                 LOC101060211 
                   
               
               
                   
               
               
                 88 
                 KPSAVKDSIY 
                 MMP26 
                 B*07/A*26 
               
               
                   
               
               
                 89 
                 FLIPRAGWLAGL 
                 SLC45A3 
                 B*07/C*06 
               
               
                   
               
               
                 90 
                 HAIEKAFQL 
                 MMP1 
                 B*07/C*04 
               
               
                   
               
               
                 91 
                 FPRLVGPDFF 
                 MMP11 
                 B*07/B*35 
               
               
                   
               
               
                 92 
                 TSPLPPTV 
                 ENPP3 
                 B*07 
               
               
                   
               
               
                 93 
                 SVAIAHGVF 
                 SLC35D3 
                 B*07/B*15 
               
               
                   
               
               
                 94 
                 LPMSKRQEY 
                 DSCR6 
                 B*07/B*35 
               
               
                   
               
               
                 95 
                 RTKEEINEL 
                 KRT121P, KRT81, KRT83, KRT85, KRT86 
                 B*07/B*57 
               
               
                   
               
               
                 96 
                 QPSLVQAIF 
                 ANKRD28 
                 B*07/B*35 
               
               
                   
               
               
                 97 
                 LPPGTQIQI 
                 ROBO3 
                 B*07 
               
               
                   
               
               
                 98 
                 FPCSALLACF 
                 FAM107B 
                 B*07/B*35 
               
               
                   
               
               
                 99 
                 MPVSAFTVI 
                 COL10A1 
                 B*07/B*51 
               
               
                   
               
               
                 100 
                 TPIPFDKILY 
                 COL10A1 
                 B*07/B*35 
               
               
                   
               
               
                 101 
                 KPGLPGLK 
                 COL10A1 
                 B*07/C*07 
               
               
                   
               
               
                 102 
                 MAGPAIHTAPM 
                 DRAXIN 
                 B*07 
               
               
                   
               
               
                 103 
                 REPIMKADML 
                 MAGEB1 
                 B*07 
               
               
                   
               
               
                 104 
                 RPLPNSVIHV 
                 TFDP3 
                 B*07 
               
               
                   
               
               
                 105 
                 RPRYETGVCA 
                 WISP3 
                 B*07 
               
               
                   
               
               
                 106 
                 APFHIDRLF 
                 NMUR2 
                 B*07 
               
               
                   
               
               
                 107 
                 GQRLESPGGAA 
                 SOX1 
                 B*07 
               
               
                   
               
               
                 108 
                 APRGSPPI 
                 FCRL5 
                 B*07 
               
               
                   
               
               
                 109 
                 LPRALMRST 
                 IGHE 
                 B*07 
               
               
                   
               
               
                 110 
                 YPSSPASAV 
                 MAGEB17 
                 B*07/B*51 
               
               
                   
               
               
                 111 
                 YPLQQTNVY 
                 SEMA5B 
                 B*07/B*35 
               
               
                   
               
               
                 112 
                 YPSPLNKHSF 
                 SEMA5B 
                 B*07/B*35 
               
               
                   
               
               
                 113 
                 KPHLDRRGAVI 
                 TSPY1, TSPY10, TSPY2, TSPY3, TSPY4, 
                 B*07 
               
               
                   
                   
                 TSPY8 
                   
               
               
                   
               
               
                 114 
                 FVPPSGPSNPM 
                 PAX3 
                 B*07 
               
               
                   
               
               
                 115 
                 KTKSLAQQL 
                 LAMC2 
                 B*07/A*30 
               
               
                   
               
               
                 116 
                 RSYQHSLRL 
                 LAMC2 
                 B*07/C*07 
               
               
                   
               
               
                 117 
                 IPHQRSSL 
                 GCSAML 
                 B*07 
               
               
                   
               
               
                 118 
                 NPERHKPSF 
                 C1orf186 
                 B*07 
               
               
                   
               
               
                 119 
                 KATEYVHSL 
                 MYCN 
                 B*07/C*16 
               
               
                   
               
               
                 120 
                 TVRPKNAAL 
                 MYCN 
                 B*07 
               
               
                   
               
               
                 121 
                 GPFQRAAL 
                 MSX1 
                 B*07 
               
               
                   
               
               
                 122 
                 KPRTPFTTAQLL 
                 MSX1 
                 B*07 
               
               
                   
               
               
                 123 
                 RPRLRDLPAL 
                 RAPGEF5 
                 B*07 
               
               
                   
               
               
                 124 
                 KTIDGHINL 
                 FAM111B 
                 B*07/C*04 
               
               
                   
               
               
                 125 
                 SPAKQFNIY 
                 FAM111B 
                 B*07/B*35 
               
               
                   
               
               
                 126 
                 MPREDAHF 
                 MLANA 
                 B*07/B*35 
               
               
                   
               
               
                 127 
                 KSKQVITLL 
                 ENTHD1 
                 B*07/C*02 
               
               
                   
               
               
                 128 
                 SPPATLFLFLL 
                 LOXL4 
                 B*07 
               
               
                   
               
               
                 129 
                 MTLPATTLTL 
                 IGHE 
                 B*07 
               
               
                   
               
               
                 130 
                 GAYDKARYL 
                 ABCC11 
                 B*07/C*06 
               
               
                   
               
               
                 131 
                 MPFRNIRSIL 
                 LOC101060288, LOC101060295, 
                 B*07 
               
               
                   
                   
                 LOC101060308, LOC645359, PRAMEF11, 
                   
               
               
                   
                   
                 PRAMEF15, PRAMEF23, PRAMEF4, 
                   
               
               
                   
                   
                 PRAMEF5, PRAMEF6, PRAMEF9 
                   
               
               
                   
               
               
                 132 
                 LPRLPVGSLV 
                 EPYC 
                 B*07/B*51 
               
               
                   
               
               
                 133 
                 LPELPTTLTF 
                 EPYC 
                 B*07 
               
               
                   
               
               
                 134 
                 VAAAARLTL 
                 ITIH6 
                 B*07 
               
               
                   
               
               
                 135 
                 MPRLLRLSL 
                 INSL6 
                 B*07 
               
               
                   
               
               
                 136 
                 QPDHAGIFRVF 
                 HEPHL1 
                 B*07 
               
               
                   
               
               
                 137 
                 SPQLSYFEY 
                 LAMC2 
                 B*07/B*35 
               
               
                   
               
               
                 138 
                 VPFNLITEY 
                 SLC45A2 
                 B*07/B*35 
               
               
                   
               
               
                 139 
                 LVILQHQAM 
                 NMUR2 
                 B*07/A*26 
               
               
                   
               
               
                 140 
                 TPFPDIHWF 
                 HMCN1 
                 B*07/B*35 
               
               
                   
               
               
                 141 
                 YGPYGSGSGW 
                 HRNR 
                 B*07 
               
               
                   
               
               
                 142 
                 HPFKMKWQY 
                 QRFPR 
                 B*07/B*35 
               
               
                   
               
               
                 143 
                 YPMIPPAQL 
                 BTBD17 
                 B*07 
               
               
                   
               
               
                 144 
                 RPVQGIPTY 
                 HMCN1 
                 B*07/B*35 
               
               
                   
               
               
                 145 
                 VPAQRLGLLL 
                 IGKV1D-43 
                 B*07 
               
               
                   
               
               
                 146 
                 SPTRGSEF 
                 PTPRZ1 
                 B*07 
               
               
                   
               
               
                 147 
                 HVAQPAVVL 
                 CTLA4 
                 B*07/C*07 
               
               
                   
               
               
                 148 
                 KPHLIYRQ 
                 ADAMTS20 
                 B*07 
               
               
                   
               
               
                 149 
                 SPSSVFTSK 
                 NAT1 
                 B*07 
               
               
                   
               
               
                 150 
                 APLHGGGSL 
                 NEFH 
                 B*07 
               
               
                   
               
               
                 151 
                 QPTWNTQTRL 
                 CLNK 
                 B*07 
               
               
                   
               
               
                 152 
                 SSASFSSELFRH 
                 PTPRZ1 
                 B*07 
               
               
                   
               
               
                 153 
                 QPVHSLCSA 
                 DPCR1 
                 B*07/B*54 
               
               
                   
               
               
                 154 
                 RPPPSRRAVL 
                 BCAN 
                 B*07 
               
               
                   
               
               
                 155 
                 APIPRLIEG 
                 CCDC38 
                 B*07 
               
               
                   
               
               
                 156 
                 GSRPVTGSV 
                 KRT121P, KRT81, KRT83 
                 B*07 
               
               
                   
               
               
                 157 
                 RPVTGSVC 
                 KRT121P, KRT81, KRT83 
                 B*07 
               
               
                   
               
               
                 158 
                 SVPVATVEL 
                 ELL3 
                 B*07/C*01 
               
               
                   
               
               
                 159 
                 TPMTVPRI 
                 KBTBD8 
                 B*07/B*51 
               
               
                   
               
               
                 160 
                 IPVSHPVLTF 
                 FCRL3 
                 B*07 
               
               
                   
               
               
                 161 
                 ASKILETSL 
                 HMCN1 
                 B*07/C*03 
               
               
                   
               
               
                 162 
                 IPIRVDQNGAF 
                 ADAMTS6 
                 B*07/B*35 
               
               
                   
               
               
                 163 
                 FRYPNGVSL 
                 RHBG 
                 B*07/C*07 
               
               
                   
               
               
                 164 
                 RAAGRRLQL 
                 RHBG 
                 B*07 
               
               
                   
               
               
                 165 
                 RPSKEMQVTI 
                 ONECUT3 
                 B*07 
               
               
                   
               
               
                 166 
                 YAYTSRVIL 
                 KBTBD8 
                 B*07/C*12 
               
               
                   
               
               
                 167 
                 NVNPARKGL 
                 DNMT3B 
                 B*07 
               
               
                   
               
               
                 168 
                 SPSGQRDVSL 
                 ENTHD1 
                 B*07 
               
               
                   
               
               
                 169 
                 RPFSVSSISQL 
                 HMCN1 
                 B*07 
               
               
                   
               
               
                 170 
                 APEGKRLGF 
                 FMN1, LOC101059984 
                 B*07 
               
               
                   
               
               
                 171 
                 LPLGGHKSL 
                 FMN1, LOC101059984 
                 B*07 
               
               
                   
               
               
                 172 
                 SAQSLHPVL 
                 POU3F4 
                 B*07/C*12 
               
               
                   
               
               
                 173 
                 VIINNPISL 
                 HMCN1 
                 B*07/C*03 
               
               
                   
               
               
                 174 
                 IPVTSSVTL 
                 KRTAP24-1 
                 B*07 
               
               
                   
               
               
                 175 
                 AAFPHKIIF 
                 SPINK13 
                 B*07/C*12/C*02 
               
               
                   
               
               
                 176 
                 QPLDICHSF 
                 ETV4 
                 B*07/B*35 
               
               
                   
               
               
                 177 
                 VWEPQGSSRSL 
                 DLX5 
                 B*07 
               
               
                   
               
               
                 178 
                 VPYYPRANL 
                 STK31 
                 B*07 
               
               
                   
               
               
                 179 
                 PRVRLLLL 
                 PTH2 
                 B*07 
               
               
                   
               
               
                 180 
                 RLRDYISSL 
                 RALGPS2 
                 B*07/C*07 
               
               
                   
               
               
                 181 
                 LPVSPARAL 
                 ADAM12 
                 B*07 
               
               
                   
               
               
                 182 
                 RPLPVSPARAL 
                 ADAM12 
                 B*07 
               
               
                   
               
               
                 183 
                 VPRRPARAL 
                 BCAN 
                 B*07 
               
               
                   
               
               
                 184 
                 KIIASGNHL 
                 ERVV-1, ERVV-2 
                 B*07 
               
               
                   
               
               
                 185 
                 RPVLTASSF 
                 FCRL2 
                 B*07 
               
               
                   
               
               
                 186 
                 VPLPAGGGTVLT 
                 GRP 
                 B*07 
               
               
                   
               
               
                 187 
                 APPPPPPPF 
                 BEND4 
                 B*07 
               
               
                   
               
               
                 188 
                 HAAASFETL 
                 FCRLA 
                 B*07/B*35 
               
               
                   
               
               
                 189 
                 QPQCSTHIL 
                 APOB 
                 B*07 
               
               
                   
               
               
                 190 
                 RLAHVRARL 
                 GREB1 
                 B*07/C*07 
               
               
                   
               
               
                 191 
                 KPKAVKPKAA 
                 HIST1H1B 
                 B*07 
               
               
                   
               
               
                 192 
                 IPFADVKSF 
                 ROS1 
                 B*07 
               
               
                   
               
               
                 193 
                 LPALKEEAF 
                 NKX3-1 
                 B*07/B*35 
               
               
                   
               
               
                 194 
                 HPNKIKASL 
                 TRPS1 
                 B*07 
               
               
                   
               
               
                 195 
                 NPIFGRKEL 
                 CAPN6 
                 B*07 
               
               
                   
               
               
                 196 
                 RPSGTAGAAL 
                 EGFR 
                 B*07 
               
               
                   
               
               
                 197 
                 RPSGTAGAALLA 
                 EGFR 
                 B*07/B*56 
               
               
                   
               
               
                 198 
                 LPSPAHAFRAL 
                 SIGLEC15 
                 B*07 
               
               
                   
               
               
                 199 
                 SPFWIHQA 
                 MPL 
                 B*07 
               
               
                   
               
               
                 200 
                 EPFHLIVSY 
                 FCRLA 
                 B*07/B*35 
               
               
                   
               
               
                 201 
                 LPIARVLTV 
                 LRP1B 
                 B*07/B*51 
               
               
                   
               
               
                 202 
                 SPSREASAL 
                 MPL 
                 B*07 
               
               
                   
               
               
                 203 
                 KPRGPIDI 
                 COL9A1 
                 B*07 
               
               
                   
               
               
                 204 
                 FPYSGDKILV 
                 VCAN 
                 B*07/B*51 
               
               
                   
               
               
                 205 
                 LPPALLTTV 
                 VCAN 
                 B*07/B*51 
               
               
                   
               
               
                 206 
                 TPRIGPKVSL 
                 VCAN 
                 B*07 
               
               
                   
               
               
                 207 
                 VPSDITTAF 
                 VCAN 
                 B*07/B*35 
               
               
                   
               
               
                 208 
                 RNRQVATAL 
                 SUCNR1 
                 B*07 
               
               
                   
               
               
                 209 
                 KIEQIRAVL 
                 LAMB3 
                 B*07 
               
               
                   
               
               
                 210 
                 IPENRVVSY 
                 CCL24 
                 B*07/B*35 
               
               
                   
               
               
                 211 
                 IPDTIASVL 
                 SLC24A5 
                 B*07 
               
               
                   
               
               
                 212 
                 VPYAAQAAL 
                 SP5 
                 B*07 
               
               
                   
               
               
                 213 
                 RPYQDAPVA 
                 SIGLEC8 
                 B*07/B*55 
               
               
                   
               
               
                 214 
                 LPLKFFPII 
                 TMPRSS3 
                 B*07 
               
               
                   
               
               
                 215 
                 IPVAIKEL 
                 EGFR 
                 B*07 
               
               
                   
               
               
                 216 
                 LPWEQNEQV 
                 APOB 
                 B*07/B*51 
               
               
                   
               
               
                 217 
                 SPGDKRLAAYL 
                 APOB 
                 B*07 
               
               
                   
               
               
                 218 
                 VQRTPPPI 
                 USH1C 
                 B*07 
               
               
                   
               
               
                 219 
                 VPHTGRYTCL 
                 HMCN1 
                 B*07 
               
               
                   
               
               
                 220 
                 RPAPGPAPFV 
                 GRIN2D 
                 B*07 
               
               
                   
               
               
                 221 
                 LPQRPNARL 
                 LAMB3 
                 B*07 
               
               
                   
               
               
                 222 
                 MLKTTLTAF 
                 APOB 
                 B*07 
               
               
                   
               
               
                 223 
                 KAHVRIEL 
                 RNF43, SUPT4H1 
                 B*07/C*16 
               
               
                   
               
               
                 224 
                 SPIIHSILL 
                 PLEKHG4B 
                 B*07 
               
               
                   
               
               
                 225 
                 SPIIHSIL 
                 PLEKHG4B 
                 B*07 
               
               
                   
               
               
                 226 
                 APGGSSRSSL 
                 IGLL1 
                 B*07 
               
               
                   
               
               
                 227 
                 RPGTGQGGL 
                 IGLL1 
                 B*07 
               
               
                   
               
               
                 228 
                 RPTAASQSRAL 
                 IGLL1 
                 B*07 
               
               
                   
               
               
                 229 
                 FPNAGPRHLL 
                 RALGPS2 
                 B*07 
               
               
                   
               
               
                 230 
                 DVIDDIISL 
                 MITF 
                 B*07/A*25 
               
               
                   
               
               
                 231 
                 SPITLQAL 
                 APOB 
                 B*07 
               
               
                   
               
               
                 232 
                 TAYPSLRLL 
                 ST8SIA2 
                 B*07/C*06 
               
               
                   
               
               
                 233 
                 MAYDRFIAI 
                 OR10V1, OR4K1, OR51B2, OR51B5, 
                 B*07/C*03 
               
               
                   
                   
                 OR9K2 
                   
               
               
                   
               
               
                 234 
                 HPRAPGEQQRL 
                 RNF43, SUPT4H1 
                 B*07 
               
               
                   
               
               
                 235 
                 AQNPAGTAL 
                 HMCN1 
                 B*07/B*15 
               
               
                   
               
               
                 236 
                 TPELKSSIL 
                 APOB 
                 B*07 
               
               
                   
               
               
                 237 
                 LPRAGGAF 
                 LAMB3 
                 B*07 
               
               
                   
               
               
                 238 
                 LPRAGGAFLM 
                 LAMB3 
                 B*07 
               
               
                   
               
               
                 239 
                 VLPRAGGAFLM 
                 LAMB3 
                 B*07 
               
               
                   
               
               
                 240 
                 RVMLPKAAL 
                 NLRP2 
                 B*07 
               
               
                   
               
               
                 241 
                 LPKAALLV 
                 NLRP2 
                 B*07/B*51 
               
               
                   
               
               
                 242 
                 IPETASWAI 
                 FCRLA 
                 B*07 
               
               
                   
               
               
                 243 
                 MARTGGMVVI 
                 UPK2 
                 B*07 
               
               
                   
               
               
                 244 
                 VPAHLVAA 
                 ESM1 
                 B*07/B*55 
               
               
                   
               
               
                 245 
                 GPVPSPLAL 
                 GDF7 
                 B*07 
               
               
                   
               
               
                 246 
                 RPILKEQSSSSF 
                 KRT13, KRT16 
                 B*07 
               
               
                   
               
               
                 247 
                 SPVGVGQRL 
                 SOX3 
                 B*07 
               
               
                   
               
               
                 248 
                 KPYDGIPAS 
                 EGFR 
                 B*07/B*56 
               
               
                   
               
               
                 249 
                 SPRSGVLL 
                 LGR5 
                 B*07 
               
               
                   
               
               
                 250 
                 APAAPAAVPS 
                 FEZF1 
                 B*07 
               
               
                   
               
               
                 251 
                 MPVDSFNSM 
                 NFE2L3 
                 B*07/C*04 
               
               
                   
               
               
                 252 
                 QPENSLEGISL 
                 NFE2L3 
                 B*07 
               
               
                   
               
               
                 253 
                 MPVDSFNSML 
                 NFE2L3 
                 B*07 
               
               
                   
               
               
                 254 
                 RVIQGTTTL 
                 PHEX 
                 B*07/A*32 
               
               
                   
               
               
                 255 
                 VPSHWMVAL 
                 CD79B 
                 B*07 
               
               
                   
               
               
                 256 
                 SPVPSHWMVAL 
                 CD79B 
                 B*07 
               
               
                   
               
               
                 257 
                 APYGTLRKS 
                 SYT12 
                 B*07 
               
               
                   
               
               
                 258 
                 SVIGPNSRL 
                 BTLA 
                 B*07/A*26 
               
               
                   
               
               
                 259 
                 VPMPGVQAV 
                 TMEM211 
                 B*07 
               
               
                   
               
               
                 260 
                 LVQSSRSEV 
                 KRT16 
                 B*07 
               
               
                   
               
               
                 261 
                 SPSTSRTPL 
                 EGFR 
                 B*07 
               
               
                   
               
               
                 262 
                 SPSTSRTPLLSSL 
                 EGFR 
                 B*07 
               
               
                   
               
               
                 263 
                 SQRPPATSQA 
                 HTR3A 
                 B*07 
               
               
                   
               
               
                 264 
                 APRPGNWIL 
                 LAMA1 
                 B*07 
               
               
                   
               
               
                 265 
                 FPRKPYEGRV 
                 LOXL3 
                 B*07 
               
               
                   
               
               
                 266 
                 KPYEGRVEI 
                 LOXL3 
                 B*07 
               
               
                   
               
               
                 267 
                 MPVPGILL 
                 PMEL 
                 B*07 
               
               
                   
               
               
                 268 
                 EPLSVTASY 
                   
                 B*07/A*25 
               
               
                   
               
               
                 269 
                 FTVSSSSAM 
                 LOC100131514, LOC101060622, MUC3A 
                 B*07/C*03 
               
               
                   
               
               
                 270 
                 SPRGTTSTL 
                   
                 B*07 
               
               
                   
               
               
                 271 
                 SPTPVFTTL 
                 LOC100131514, LOC101060622, 
                 B*07 
               
               
                   
                   
                 LOC101060740, LOC101060797, MUC3A, 
                   
               
               
                   
                   
                 MUC3B 
                   
               
               
                   
               
               
                 272 
                 SSPRGTTSTL 
                   
                 B*07 
               
               
                   
               
               
                 273 
                 TDTPSTTPTTI 
                 MUC3A 
                 B*07 
               
               
                   
               
               
                 274 
                 KPIRTGISPLAL 
                 APOB 
                 B*07 
               
               
                   
               
               
                 275 
                 IPAPQGAVL 
                 KISS1 
                 B*07 
               
               
                   
               
               
                 276 
                 RPVWDVRSA 
                 RNASE10 
                 B*07/B*55 
               
               
                   
               
               
                 277 
                 MPPLLIVAF 
                 HCAR1 
                 B*07/B*35 
               
               
                   
               
               
                 278 
                 LIAARGSLVL 
                 NTN3 
                 B*07 
               
               
                   
               
               
                 279 
                 APADEPRTVL 
                 SAPCD2 
                 B*07 
               
               
                   
               
               
                 280 
                 LPRAFLQSL 
                 SAPCD2 
                 B*07 
               
               
                   
               
               
                 281 
                 NPRSPPATM 
                 SIGLEC15 
                 B*07 
               
               
                   
               
               
                 282 
                 AVRLPTPNL 
                 MPL 
                 B*07 
               
               
                   
               
               
                 283 
                 RPQPGWRESL 
                 FMR1NB 
                 B*07 
               
               
                   
               
               
                 284 
                 RPSAPRGPP 
                 ASCL2 
                 B*07 
               
               
                   
               
               
                 285 
                 RITWKGLLL 
                 PSG3, PSG8, PSG9 
                 B*07/C*07 
               
               
                   
               
               
                 286 
                 APARPAAAF 
                 TDRD9 
                 B*07 
               
               
                   
               
               
                 287 
                 SPIPRPLFL 
                 SYCP2 
                 B*07 
               
               
                   
               
               
                 288 
                 LHAMNSLSAM 
                 DMBX1 
                 B*07 
               
               
                   
               
               
                 289 
                 LPYEKVSRL 
                 CHST4 
                 B*07 
               
               
                   
               
               
                 290 
                 RPTHPLRSF 
                 DCC 
                 B*07 
               
               
                   
               
               
                 291 
                 SPSKSLEM 
                 L1TD1 
                 B*07 
               
               
                   
               
               
                 292 
                 LPMTHRLQL 
                 PSG4, PSG5, PSG6, PSG7 
                 B*07 
               
               
                   
               
               
                 293 
                 FPYDKPLIM 
                 MET 
                 B*07/B*51 
               
               
                   
               
               
                 294 
                 VPKPAIPSSSVL 
                 DCC 
                 B*07 
               
               
                   
               
               
                 295 
                 HPRWIEPTVM 
                 HOXA13 
                 B*07 
               
               
                   
               
               
                 296 
                 SPLLMQRTL 
                 TFEC 
                 B*07/B*51 
               
               
                   
               
               
                 297 
                 FPIKYVNDF 
                 MET 
                 B*07/B*35 
               
               
                   
               
               
                 298 
                 RVLLRWISL 
                 ILDR2 
                 B*07 
               
               
                   
               
               
                 299 
                 SPFSGGPVSF 
                 POU5F1, POU5F1B 
                 B*07 
               
               
                   
               
               
                 300 
                 HPYSDLADVF 
                 RTL1 
                 B*07 
               
               
                   
               
               
                 301 
                 FPAFLEAM 
                 RTL1 
                 B*07/B*35 
               
               
                   
               
               
                 302 
                 IPIDQILNSF 
                 RTL1 
                 B*07/B*35 
               
               
                   
               
               
                 303 
                 RPPPPCIAL 
                 RTL1 
                 B*07 
               
               
                   
               
               
                 304 
                 SPLIGDFPAF 
                 RTL1 
                 B*07/B*35 
               
               
                   
               
               
                 305 
                 AASPVGSAL 
                 SLC16A11 
                 B*07/C*03 
               
               
                   
               
               
                 306 
                 RPFPLALL 
                 CYP2W1 
                 B*07 
               
               
                   
               
               
                 307 
                 RPHQKGWLSI 
                 KLB 
                 B*07 
               
               
                   
               
               
                 308 
                 RPDVVRTLL 
                 ARSI 
                 B*07 
               
               
                   
               
               
                 309 
                 FAFYGGKSL 
                 SLC44A5 
                 B*07/C*03 
               
               
                   
               
               
                 310 
                 SPGWAQTQL 
                 MACC1 
                 B*07 
               
               
                   
               
               
                 311 
                 APRLALDPDAL 
                 AMH 
                 B*07 
               
               
                   
               
               
                 312 
                 SPSLQSSRESL 
                 KIF26B 
                 B*07 
               
               
                   
               
               
                 313 
                 VPLSSYVSI 
                 PCDHGA11 
                 B*07 
               
               
                   
               
               
                 314 
                 IALMKLAGPL 
                 TMPRSS3 
                 B*07 
               
               
                   
               
               
                 315 
                 APVVFPAL 
                 GSC 
                 B*07 
               
               
                   
               
               
                 316 
                 NPREPEKSL 
                 LOC100124692 
                 B*07 
               
               
                   
               
               
                 317 
                 MPYNSAHHCVV 
                 KLHL14 
                 B*07/B*51 
               
               
                   
               
               
                 318 
                 TPISNTGVL 
                 SIGLEC6 
                 B*07 
               
               
                   
               
               
                 319 
                 RPLDTFRVL 
                 EVX1 
                 B*07 
               
               
                   
               
               
                 320 
                 APMHIDRNIL 
                 SLC10A5 
                 B*07 
               
               
                   
               
               
                 321 
                 QPQQPGFFL 
                 MED12L 
                 B*07 
               
               
                   
               
               
                 322 
                 RAVPVGSGL 
                 TRIT1 
                 B*07/C*03 
               
               
                   
               
               
                 323 
                 TPHGITDIL 
                 NKX6-3 
                 B*07 
               
               
                   
               
               
                 324 
                 LPAPLRISL 
                 GPR45 
                 B*07 
               
               
                   
               
               
                 325 
                 SPRSNPVRL 
                 FCRL4 
                 B*07 
               
               
                   
               
               
                 326 
                 IPPFTQRVF 
                 RASSF9 
                 B*07/B*35 
               
               
                   
               
               
                 327 
                 GPRTTQSSVL 
                 SIGLEC6 
                 B*07 
               
               
                   
               
               
                 328 
                 LPLHRGDLVI 
                 DNMBP 
                 B*07/B*51 
               
               
                   
               
               
                 329 
                 QPANFIVLL 
                 LOC100124692 
                 B*07 
               
               
                   
               
               
                 330 
                 RPFSAIAEL 
                 MORC4 
                 B*07 
               
               
                   
               
               
                 331 
                 SPDSAILKL 
                 ZNF827 
                 B*07 
               
               
                   
               
               
                 332 
                 SPYAGSTAF 
                 IRX5 
                 B*07 
               
               
                   
               
               
                 333 
                 SVLPRALSL 
                 C5orf34 
                 B*07/C*07 
               
               
                   
               
               
                 334 
                 YPLSLALHF 
                 C5orf34 
                 B*07/B*35 
               
               
                   
               
               
                 335 
                 VPPQNPRPSL 
                 RUNX2 
                 B*07 
               
               
                   
               
               
                 336 
                 YPLQGPGLLSV 
                 NUP155 
                 B*07/B*51 
               
               
                   
               
               
                 337 
                 IPTSRVITL 
                 NUGGC 
                 B*07 
               
               
                   
               
               
                 338 
                 MPATPSLKV 
                 TRIM15 
                 B*07 
               
               
                   
               
               
                 339 
                 GPQRTTSV 
                 DTX1 
                 B*07 
               
               
                   
               
               
                 340 
                 APEPRAALL 
                 UAP1L1 
                 B*07 
               
               
                   
               
               
                 341 
                 LPRSPPLKVL 
                 RMI2 
                 B*07 
               
               
                   
               
               
                 342 
                 RPRPPKVL 
                 TXNRD1 
                 B*07 
               
               
                   
               
               
                 343 
                 RPRPPKVLGL 
                 TXNRD1 
                 B*07 
               
               
                   
               
               
                 344 
                 VPYPSPTCV 
                 AR 
                 B*07 
               
               
                   
               
               
                 345 
                 SAAPPGASL 
                 AR 
                 B*07/C*03 
               
               
                   
               
               
                 346 
                 IPMPRITWL 
                 FSTL4 
                 B*07 
               
               
                   
               
               
                 347 
                 SPLEKINSF 
                 BRIP1 
                 B*07 
               
               
                   
               
               
                 348 
                 HPAPPVTSA 
                 STON2 
                 B*07/B*54 
               
               
                   
               
               
                 349 
                 QPRDGWPMML 
                 STON2 
                 B*07 
               
               
                   
               
               
                 350 
                 RPKSTLMNF 
                 STON2 
                 B*07 
               
               
                   
               
               
                 351 
                 SPYADIIPSA 
                 GLI3 
                 B*07/B*54 
               
               
                   
               
               
                 352 
                 LPAFSKIGGIL 
                 IQGAP3 
                 B*07 
               
               
                   
               
               
                 353 
                 KPRATWTL 
                 RTP4 
                 B*07 
               
               
                   
               
               
                 354 
                 APAKDARASL 
                 TRIO 
                 B*07 
               
               
                   
               
               
                 355 
                 APKTSFIAA 
                 GALNT5 
                 B*07/B*55 
               
               
                   
               
               
                 356 
                 RPFLRLPSL 
                 UCHL3 
                 B*07 
               
               
                   
               
               
                 357 
                 LPPHIFAI 
                 MYO10 
                 B*07/B*51 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 1b 
               
             
            
               
                   
               
               
                 Peptides according to the present invention. 
               
            
           
           
               
               
               
            
               
                 Seq 
                   
                   
               
               
                 ID No. 
                 Sequence 
                 Gene(s) 
               
               
                   
               
               
                 448 
                 TVYGEPRKL 
                 MAGEA4 
               
               
                   
               
               
                 449 
                 RPKTSVNLISSL 
                 MMP12 
               
               
                   
               
               
                 450 
                 SAAARALLP 
                 MMP11 
               
               
                   
               
               
                 451 
                 VPILPLNHAL 
                 PGR 
               
               
                   
               
               
                 452 
                 QPVKKNTL 
                 ENPP3 
               
               
                   
               
               
                 453 
                 APALPGQVTI 
                 MEX3A 
               
               
                   
               
               
                 454 
                 SPDPAHLESL 
                 MAGEA8 
               
               
                   
               
               
                 455 
                 FPVQATIDF 
                 DSCR6 
               
               
                   
               
               
                 456 
                 VPVSHPVLTL 
                 FCRL5 
               
               
                   
               
               
                 457 
                 RPPLSQRHTF 
                 CLNK 
               
               
                   
               
               
                 458 
                 VPIPTHYFVVL 
                 ENPP3, OR2A4 
               
               
                   
               
               
                 459 
                 SPAPWRPWI 
                 DSCR6 
               
               
                   
               
               
                 460 
                 APLMPLGKTL 
                 LAMC2 
               
               
                   
               
               
                 461 
                 MPHLGPGILL 
                 ITIH6 
               
               
                   
               
               
                 462 
                 MPLLADVRL 
                 ITIH6 
               
               
                   
               
               
                 463 
                 LPTDLFNSVM 
                 ROPN1, ROPN1B 
               
               
                   
               
               
                 464 
                 VPFVPRTSV 
                 NFE2L3 
               
               
                   
               
               
                 465 
                 VPKSLPYVL 
                 GTSF1 
               
               
                   
               
               
                 466 
                 SPMEAILVSRL 
                 MAP7D2 
               
               
                   
               
               
                 467 
                 VPRNQDWLGVSRQL 
                 PMEL 
               
               
                   
               
               
                 468 
                 LPSLHVLVL 
                 DCT 
               
               
                   
               
               
                 469 
                 LPLDTRTSI 
                 CLNK 
               
               
                   
               
               
                 470 
                 RPNGEVKSEL 
                 GRM8 
               
               
                   
               
               
                 471 
                 LPLLAGTLLL 
                 ALPI, ALPP, ALPPL2 
               
               
                   
               
               
                 472 
                 LPMPAITWY 
                 HMCN1 
               
               
                   
               
               
                 473 
                 LPGEREAAL 
                 FMN1, LOC101059984 
               
               
                   
               
               
                 474 
                 VPKADLLTL 
                 FMN1, LOC101059984 
               
               
                   
               
               
                 475 
                 IPLEIQKL 
                 CDRT1, FBXW10 
               
               
                   
               
               
                 476 
                 EPNPVEEIF 
                 COL11A1 
               
               
                   
               
               
                 477 
                 NPVPVITWYKDNRL 
                 HMCN1 
               
               
                   
               
               
                 478 
                 APKFISPASQL 
                 GRM8 
               
               
                   
               
               
                 479 
                 APHAGGALL 
                 MIXL1 
               
               
                   
               
               
                 480 
                 VPAAPTKAL 
                 SPOCD1 
               
               
                   
               
               
                 481 
                 SPARALLLALA 
                 ADAM12 
               
               
                   
               
               
                 482 
                 QPSLKKIIL 
                 INSL4 
               
               
                   
               
               
                 483 
                 KPAAAGVKKVA 
                 HIST1H1B 
               
               
                   
               
               
                 484 
                 LPASAEPKGTM 
                 OFCC1 
               
               
                   
               
               
                 485 
                 LPLKTKVFA 
                 ZPLD1 
               
               
                   
               
               
                 486 
                 TPTRPLPSA 
                 USH1C 
               
               
                   
               
               
                 487 
                 IPWFIKTAF 
                 SLC24A5 
               
               
                   
               
               
                 488 
                 LPLGGLPLLI 
                 BTLA 
               
               
                   
               
               
                 489 
                 WPNHIMLVL 
                 GREB1, GREB1L 
               
               
                   
               
               
                 490 
                 APRGPAQGEAA 
                 RUNX1 
               
               
                   
               
               
                 491 
                 MPEADLKRIF 
                 SLC24A5 
               
               
                   
               
               
                 492 
                 IPFSVDEI 
                 NFE2L3 
               
               
                   
               
               
                 493 
                 LPLQQYKLV 
                 FEZF1 
               
               
                   
               
               
                 494 
                 LPLRAVNLNL 
                 FAM64A 
               
               
                   
               
               
                 495 
                 SPSYTQASL 
                 TRPS1 
               
               
                   
               
               
                 496 
                 MPAVSGPGPLF 
                 LMAN1L 
               
               
                   
               
               
                 497 
                 YVVKPLHPF 
                 ROS1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2a 
               
             
            
               
                   
               
               
                 Additional peptides according to the present 
               
               
                 invention with no prior known cancer association. 
               
            
           
           
               
               
               
            
               
                 SEQ ID 
                   
                   
               
               
                 No. 
                 Sequence 
                 Official Gene Symbol(s) 
               
               
                   
               
               
                 358 
                 APSMLRKNQL 
                 DCAF4L2 
               
               
                   
               
               
                 359 
                 SPRRLVELAGQSL 
                 PRAME 
               
               
                   
               
               
                 360 
                 SPASRSISLL 
                 CD70 
               
               
                   
               
               
                 361 
                 SPYGSDRLVQL 
                 ZBTB32 
               
               
                   
               
               
                 362 
                 KPMLPPAAF 
                 MSX1 
               
               
                   
               
               
                 363 
                 KPRTPFTTA 
                 MSX1 
               
               
                   
               
               
                 364 
                 KPRTPFTTAQL 
                 MSX1 
               
               
                   
               
               
                 365 
                 RPKHFLQML 
                 NLRP7 
               
               
                   
               
               
                 366 
                 SPTLRQLDL 
                 NLRP11 
               
               
                   
               
               
                 367 
                 APQVHIFSL 
                 OXTR 
               
               
                   
               
               
                 368 
                 NPASRLTAL 
                 BMPR1A, BMPR1B 
               
               
                   
               
               
                 369 
                 RPYGCVLRAA 
                 CD70 
               
               
                   
               
               
                 370 
                 AAHEFGHVL 
                 MMP11 
               
               
                   
               
               
                 371 
                 APRSPGQVTPRGL 
                 C6orf223 
               
               
                   
               
               
                 372 
                 SPSSASLTL 
                 FAM227B 
               
               
                   
               
               
                 373 
                 LPKPDLPQLI 
                 DEFB132 
               
               
                   
               
               
                 374 
                 KPRNMTGLDL 
                 CLEC17A 
               
               
                   
               
               
                 375 
                 LPRGVLEGL 
                 SAPCD2 
               
               
                   
               
               
                 376 
                 FPQVGRTAL 
                 CXCR3 
               
               
                   
               
               
                 377 
                 SPFSKRIKL 
                 BCL11A 
               
               
                   
               
               
                 378 
                 SPRQPRLDF 
                 E2F7 
               
               
                   
               
               
                 379 
                 GPRQVLFPL 
                 PCDHGB6, PCDHGB7 
               
               
                   
               
               
                 380 
                 SPYPGSAAF 
                 IRX2 
               
               
                   
               
               
                 381 
                 APRPRLLLL 
                 TGFBR1 
               
               
                   
               
               
                 382 
                 RPGPQRTTSV 
                 DTX1 
               
               
                   
               
               
                 383 
                 KPRATWTLKL 
                 RTP4 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2b 
               
             
            
               
                   
               
               
                 Additional peptides according to the present 
               
               
                 invention with no prior known cancer association. 
               
            
           
           
               
               
               
            
               
                 Seq ID No 
                 Sequence 
                 Gene(s) 
               
               
                   
               
               
                 498 
                 RPQPQPRPAL 
                 WNT10A 
               
               
                   
               
               
                 499 
                 QPVLPSPAC 
                 PMEL 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Peptides of the invention useful for e.g. 
               
               
                 personalized cancer therapies. 
               
            
           
           
               
               
               
            
               
                 SEQ ID 
                   
                   
               
               
                 No. 
                 Sequence 
                 Official Gene Symbol(s) 
               
               
                   
               
               
                 384 
                 APLLLARAA 
                 ACPP 
               
               
                   
               
               
                 385 
                 FPSLREAAL 
                 MAGEA1 
               
               
                   
               
               
                 386 
                 YPLRGSSI 
                 ALPP, ALPPL2 
               
               
                   
               
               
                 387 
                 MPMQDIKM 
                 PRAME 
               
               
                   
               
               
                 388 
                 SPSVSQLSVL 
                 PRAME 
               
               
                   
               
               
                 389 
                 APLPRPGAVL 
                 CTAG2 
               
               
                   
               
               
                 390 
                 SPRMSGLLSQT 
                 DLL3 
               
               
                   
               
               
                 391 
                 APRPASSL 
                 MMP11 
               
               
                   
               
               
                 392 
                 GPQPWHAAL 
                 MMP11 
               
               
                   
               
               
                 393 
                 APAAWLRSA 
                 MMP11 
               
               
                   
               
               
                 394 
                 APAAWLRSAA 
                 MMP11 
               
               
                   
               
               
                 395 
                 APAAWLRSAAA 
                 MMP11 
               
               
                   
               
               
                 396 
                 VPDVAQFVL 
                 MMP1 
               
               
                   
               
               
                 397 
                 GPALGRSFL 
                 CD70 
               
               
                   
               
               
                 398 
                 SPASRSISL 
                 CD70 
               
               
                   
               
               
                 399 
                 NPFYPEVEL 
                 MMP1 
               
               
                   
               
               
                 400 
                 TIASQRLTPL 
                 CD70 
               
               
                   
               
               
                 401 
                 RPAPADSAL 
                 KISS1R 
               
               
                   
               
               
                 402 
                 LPSPVDAAF 
                 MMP11 
               
               
                   
               
               
                 403 
                 RGVPSEIDAAF 
                 MMP11 
               
               
                   
               
               
                 404 
                 VPSEIDAAF 
                 MMP11 
               
               
                   
               
               
                 405 
                 LPFDGPGGIL 
                 MMP11 
               
               
                   
               
               
                 406 
                 LPDGSRVEL 
                 ACTL8 
               
               
                   
               
               
                 407 
                 FPRLVGPDF 
                 MMP11 
               
               
                   
               
               
                 408 
                 YPKDIYSSF 
                 MMP1 
               
               
                   
               
               
                 409 
                 IPASHPVL 
                 FCRL5 
               
               
                   
               
               
                 410 
                 SPRSWIQVQI 
                 FCRL5 
               
               
                   
               
               
                 411 
                 IPNWARQDL 
                 NLRP7 
               
               
                   
               
               
                 412 
                 HPSAHDVIL 
                 LAMC2 
               
               
                   
               
               
                 413 
                 SVHKITSTF 
                 LAMC2 
               
               
                   
               
               
                 414 
                 KPSESIYSAL 
                 FAM111B 
               
               
                   
               
               
                 415 
                 LPSDSHFKITF 
                 FAM111B 
               
               
                   
               
               
                 416 
                 RAKNAGVTI 
                 LAMC2 
               
               
                   
               
               
                 417 
                 VPRPIFSQL 
                 GREB1, GREB1L 
               
               
                   
               
               
                 418 
                 RPMTPTQIGPSL 
                 TCL1A 
               
               
                   
               
               
                 419 
                 SPMWHVQQL 
                 QRFPR 
               
               
                   
               
               
                 420 
                 SPRWLPVSL 
                 BTBD17 
               
               
                   
               
               
                 421 
                 FPTEVTPHAF 
                 PTPRZ1 
               
               
                   
               
               
                 422 
                 IPVSHPVL 
                 FCRL3 
               
               
                   
               
               
                 423 
                 SPRVYWLGL 
                 CLEC17A 
               
               
                   
               
               
                 424 
                 YPRGNHWAVGH 
                 GRP 
               
               
                   
               
               
                 425 
                 YPRGNHWAVGHL 
                 GRP 
               
               
                   
               
               
                 426 
                 RYLPNPSLNAF 
                 CYP1A1 
               
               
                   
               
               
                 427 
                 VPSSRILQL 
                 THEG 
               
               
                   
               
               
                 428 
                 SPADAHRNL 
                 NLRP2 
               
               
                   
               
               
                 429 
                 RPRALRDLQL 
                 NLRP7 
               
               
                   
               
               
                 430 
                 RPRALRDLQLL 
                 NLRP7 
               
               
                   
               
               
                 431 
                 VPLPAGGGTV 
                 GRP 
               
               
                   
               
               
                 432 
                 VPLPAGGGTVL 
                 GRP 
               
               
                   
               
               
                 433 
                 IPEPSAQQL 
                 APOB 
               
               
                   
               
               
                 434 
                 LPRIPFADV 
                 ROS1 
               
               
                   
               
               
                 435 
                 MPLSTIREV 
                 CDK6 
               
               
                   
               
               
                 436 
                 RPMQQARAQL 
                 KLHDC7B 
               
               
                   
               
               
                 437 
                 FPYPYAERL 
                 GRIN2D 
               
               
                   
               
               
                 438 
                 LPRAGGAFL 
                 LAMB3 
               
               
                   
               
               
                 439 
                 NPFPHLITL 
                 ROS1 
               
               
                   
               
               
                 440 
                 YPRTITPGM 
                 KLK14 
               
               
                   
               
               
                 441 
                 SPVPSHWMVA 
                 CD79B 
               
               
                   
               
               
                 442 
                 SPSTSRTPLL 
                 EGFR 
               
               
                   
               
               
                 443 
                 VPDGVSKVL 
                 APOB 
               
               
                   
               
               
                 444 
                 RVEEVRALL 
                 CDKN2A 
               
               
                   
               
               
                 445 
                 RPAATAVISL 
                 SLC7A11 
               
               
                   
               
            
           
         
       
     
     The present invention furthermore generally relates to the peptides according to the present invention for use in the treatment of proliferative diseases, such as, for example, acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer. 
     Particularly preferred are the peptides—alone or in combination—according to the present invention selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499. More preferred are the peptides—alone or in combination—selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 79 (see Table 1a), and their uses in the immunotherapy of cancer, and preferably acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer. 
     Thus, another aspect of the present invention relates to the use of the peptides according to the present invention for the—preferably combined—treatment of a proliferative disease selected from the group of acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer. 
     The present invention furthermore 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 an elongated form, such as a length-variant—MHC class-II. 
     The present invention further relates to the peptides according to the present invention wherein said peptides (each) consist or consist essentially of an amino acid sequence according to SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499. 
     The present invention further relates to the peptides according to the present invention, wherein said peptide is modified and/or includes 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 to the N-terminal amino acids of the HLA-DR antigen-associated invariant chain (Ii), or fused to (or 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, encoding the peptides according to the present invention. The present invention further relates to the nucleic acid according to the present invention that is DNA, cDNA, PNA, RNA or combinations thereof. 
     The present invention further relates to an expression vector capable of expressing and/or 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 the treatment of diseases and in medicine, in particular in the treatment of cancer. 
     The present invention further relates to antibodies that are specific against the peptides according to the present invention or complexes of said peptides according to the present invention with MHC, and methods of making these. 
     The present invention further relates to T-cell receptors (TCRs), in particular soluble TCR (sTCRs) and cloned TCRs engineered into autologous or allogeneic T cells, and methods of making these, as well as NK cells or other cells bearing said TCR or cross-reacting with said TCRs. 
     The antibodies and TCRs are additional embodiments of the immunotherapeutic use of the peptides according to the invention at hand. 
     The present invention further relates to a host cell comprising a nucleic acid according to the present invention or an expression vector as described before. The present invention further relates to the host cell according to the present invention that 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, said method comprising culturing the host cell according to the present invention, and isolating the peptide from said host cell or its culture medium. 
     The present invention further relates to said method according to the present invention, wherein the antigen is loaded onto class I or II MHC molecules expressed on the surface of a suitable antigen-presenting cell or artificial antigen-presenting cell by contacting a sufficient amount of the antigen with an antigen-presenting cell. 
     The present invention further relates to the method according to the present invention, wherein the antigen-presenting cell comprises an expression vector capable of expressing or expressing said peptide containing SEQ ID No. 1 to SEQ ID No.: 383 and SEQ ID NO: 448 to SEQ ID NO: 499, preferably containing SEQ ID No. 1 to SEQ ID No. 79, or a variant amino acid sequence. 
     The present invention further relates to activated T cells, produced by the method according to the present invention, wherein said T cell selectively recognizes a cell which expresses a polypeptide comprising an amino acid sequence according to the present invention. 
     In an aspect, the activated T cells may be produced by contacting in vitro T cells with antigen loaded human class I or II MHC molecules presented on the surface of a suitable antigen-presenting cell or an artificial construct mimicking an antigen-presenting cell for a period of time sufficient to activate said T cells. 
     The present invention further relates to a method of killing target cells in a patient, in which the target cells aberrantly express a polypeptide comprising any amino acid sequence according to the present invention, the method comprising administering to the patient an effective number of T cells as produced according to the present invention. 
     The present invention further relates to a method of treating a patient who has cancer, in which the cancer cells aberrantly express a polypeptide comprising any amino acid sequence according to the present invention, the method comprising administering to the patient an effective number of T cells as produced according to the present invention. 
     The present invention further relates to a method of eliciting an immune response in a patient who has cancer, in which the cancer cells aberrantly express a polypeptide comprising any amino acid sequence according to the present invention, the method comprising administering to the patient an effective number of T cells as produced according to the present invention. 
     In one aspect, the immune response may include cytotoxic T cell response. 
     The present invention further relates to the use of any peptide as described, the nucleic acid according to the present invention, the expression vector according to the present invention, the cell according to the present invention, the activated T lymphocyte, the T cell receptor or the antibody or other peptide- and/or peptide-MHC-binding molecules according to the present invention as a medicament or in the manufacture of a medicament. Preferably, said medicament is active against cancer. 
     Preferably, said medicament is a cellular therapy, a vaccine or a protein based on a soluble TCR or antibody. 
     The present invention further relates to a use according to the present invention, wherein said cancer cells are acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer, and preferably acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer cells. 
     The present invention further relates to biomarkers based on the peptides according to the present invention, herein called “targets” that can be used in the diagnosis of cancer, preferably acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer. The marker can be over-presentation of the peptide(s) themselves, or over-expression of the corresponding gene(s). The markers may also be used to predict the probability of success of a treatment, preferably an immunotherapy, and most preferred an immunotherapy targeting the same target that is identified by the biomarker. For example, an antibody or soluble TCR can be used to stain sections of the tumor to detect the presence of a peptide of interest in complex with MHC. 
     Optionally the antibody carries a further effector function such as an immune stimulating domain or toxin. 
     The present invention also relates to the use of these novel targets in the context of cancer treatment. 
     Stimulation of an immune response is dependent upon the presence of antigens recognized as foreign by the host immune system. The discovery of the existence of tumor associated antigens has raised the possibility of using a host&#39;s immune system to intervene in tumor growth. Various mechanisms of harnessing both the humoral and cellular arms of the immune system are currently being explored for cancer immunotherapy. 
     Specific elements of the cellular immune response are capable of specifically recognizing and destroying tumor cells. The isolation of T-cells from tumor-infiltrating cell populations or from peripheral blood suggests that such cells play a significant role in natural immune defense against cancer. CD8-positive T-cells in particular, which recognize class I molecules of the major histocompatibility complex (MHC)-bearing peptides of usually 8 to 10 amino acid residues derived from proteins or defect ribosomal products (DRIPS) located in the cytosol, play a significant role in this response. The MHC-molecules of the human are also designated as human leukocyte-antigens (HLA). 
     As used herein and except as noted otherwise all terms are defined as given below. 
     The term “T-cell response” means the specific proliferation and activation of effector functions induced by a peptide in vitro or in vivo. For MHC class I restricted cytotoxic T cells, effector functions may be lysis of peptide-pulsed, peptide-precursor pulsed or naturally peptide-presenting target cells, secretion of cytokines, preferably Interferon-gamma, TNF-alpha, or IL-2 induced by peptide, secretion of effector molecules, preferably granzymes or perforins induced by peptide, or degranulation. 
     The term “peptide” is used herein to designate a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids. The peptides are preferably 9 amino acids in length but can be as short as 8 amino acids in length, and as long as 10, 11, 12, or 13 or longer, and in case of MHC class II peptides (elongated variants of the peptides of the invention) they can be as long as 14, 15, 16, 17, 18, 19 or 20 or more amino acids in length. 
     Furthermore, the term “peptide” shall include salts of a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids. Preferably, the salts are pharmaceutical acceptable salts of the peptides, such as, for example, the chloride or acetate (trifluoroacetate) salts. It has to be noted that the salts of the peptides according to the present invention differ substantially from the peptides in their state(s) in vivo, as the peptides are not salts in vivo. 
     The term “peptide” shall also include “oligopeptide”. The term “oligopeptide” is used herein to designate a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids. The length of the oligopeptide is not critical to the invention, as long as the correct epitope or epitopes are maintained therein. The oligopeptides are typically less than about 30 amino acid residues in length, and greater than about 15 amino acids in length. 
     The term “polypeptide” designates a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids. The length of the polypeptide is not critical to the invention as long as the correct epitopes are maintained. In contrast to the terms peptide or oligopeptide, the term polypeptide is meant to refer to molecules containing more than about 30 amino acid residues. 
     A peptide, oligopeptide, protein or polynucleotide coding for such a molecule is “immunogenic” (and thus is an “immunogen” within 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 induce a T-cell response. Thus, an “immunogen” would be a molecule that is capable of inducing an immune response, and in the case of the present invention, a molecule capable of inducing a T-cell response. In another aspect, the immunogen can be the peptide, the complex of the peptide with MHC, oligopeptide, and/or protein that is used to raise specific antibodies or TCRs against it. 
     A class I T cell “epitope” requires a short peptide that is bound to a class I MHC receptor, forming a ternary complex (MHC class I alpha chain, beta-2-microglobulin, and peptide) that can be recognized by a T cell bearing a matching T-cell receptor binding to the MHC/peptide complex with appropriate affinity. Peptides binding to MHC class I molecules are typically 8-14 amino acids in length, and most typically 9 amino acids in length. 
     In humans there are three different genetic loci that encode MHC class I molecules (the MHC-molecules of the human are also designated 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 4 
               
             
            
               
                   
               
               
                 Expression frequencies F of HLA-A*02, HLA-A*01, HLA-A*03, HLA-A*24, HLA- 
               
               
                 B*07, HLA-B*08 and HLA-B*44 serotypes. Haplotype frequencies Gf are derived from a 
               
               
                 study which used HLA-typing data from a registry of more than 6.5 million volunteer 
               
               
                 donors in the U.S. (Gragert et al., 2013). The haplotype frequency is the frequency of a 
               
               
                 distinct allele on an individual chromosome. Due to the diploid set of chromosomes 
               
               
                 within mammalian cells, the frequency of genotypic occurrence of this allele is higher, 
               
               
                 and can be calculated employing the Hardy-Weinberg principle (F = 1 − (1 − Gf) 2 ). 
               
            
           
           
               
               
               
            
               
                   
                   
                 Calculated phenotype 
               
               
                 Allele 
                 Population 
                 from allele frequency (F) 
               
               
                   
               
            
           
           
               
               
               
            
               
                 A*02 
                 African (N = 28557) 
                 32.3% 
               
               
                   
                 European Caucasian 
                 49.3% 
               
               
                   
                 (N = 1242890) 
                   
               
               
                   
                 Japanese (N = 24582) 
                 42.7% 
               
               
                   
                 Hispanic, S + Cent Amer. 
                 46.1% 
               
               
                   
                 (N = 146714) 
                   
               
               
                   
                 Southeast Asian (N = 27978) 
                 30.4% 
               
               
                 A*01 
                 African (N = 28557) 
                 10.2% 
               
               
                   
                 European Caucasian 
                 30.2% 
               
               
                   
                 (N = 1242890) 
                   
               
               
                   
                 Japanese (N = 24582) 
                 1.8% 
               
               
                   
                 Hispanic, S + Cent Amer. 
                 14.0% 
               
               
                   
                 (N = 146714) 
                   
               
               
                   
                 Southeast Asian (N = 27978) 
                 21.0% 
               
               
                 A*03 
                 African (N = 28557) 
                 14.8% 
               
               
                   
                 European Caucasian 
                 26.4% 
               
               
                   
                 (N = 1242890) 
                   
               
               
                   
                 Japanese (N = 24582) 
                 1.8% 
               
               
                   
                 Hispanic, S + Cent Amer. 
                 14.4% 
               
               
                   
                 (N = 146714) 
                   
               
               
                   
                 Southeast Asian (N = 27978) 
                 10.6% 
               
               
                 A*24 
                 African (N = 28557) 
                 2.0% 
               
               
                   
                 European Caucasian 
                 8.6% 
               
               
                   
                 (N = 1242890) 
                   
               
               
                   
                 Japanese (N = 24582) 
                 35.5% 
               
               
                   
                 Hispanic, S + Cent Amer. 
                 13.6% 
               
               
                   
                 (N = 146714) 
                   
               
               
                   
                 Southeast Asian (N = 27978) 
                 16.9% 
               
               
                 B*07 
                 African (N = 28557) 
                 14.7% 
               
               
                   
                 European Caucasian 
                 25.0% 
               
               
                   
                 (N = 1242890) 
                   
               
               
                   
                 Japanese (N = 24582) 
                 11.4% 
               
               
                   
                 Hispanic, S + Cent Amer. 
                 12.2% 
               
               
                   
                 (N = 146714) 
                   
               
               
                   
                 Southeast Asian (N = 27978) 
                 10.4% 
               
               
                 B*08 
                 African (N = 28557) 
                 6.0% 
               
               
                   
                 European Caucasian 
                 21.6% 
               
               
                   
                 (N = 1242890) 
                   
               
               
                   
                 Japanese (N = 24582) 
                 1.0% 
               
               
                   
                 Hispanic, S + Cent Amer. 
                 7.6% 
               
               
                   
                 (N = 146714) 
                   
               
               
                   
                 Southeast Asian (N = 27978) 
                 6.2% 
               
               
                 B*44 
                 African (N = 28557) 
                 10.6% 
               
               
                   
                 European Caucasian 
                 26.9% 
               
               
                   
                 (N = 1242890) 
                   
               
               
                   
                 Japanese (N = 24582) 
                 13.0% 
               
               
                   
                 Hispanic, S + Cent Amer. 
                 18.2% 
               
               
                   
                 (N = 146714) 
                   
               
               
                   
                 Southeast Asian (N = 27978) 
                 13.1% 
               
               
                   
               
            
           
         
       
     
     The peptides of the invention, preferably when included into a vaccine of the invention as described herein bind to B*07. A vaccine may also include pan-binding MHC class II peptides. Therefore, the vaccine of the invention can be used to treat cancer in patients that are B*07-positive, whereas no selection for MHC class II allotypes is necessary due to the pan-binding nature of these peptides. 
     If B*07 peptides of the invention are combined with peptides binding to another allele, for example A*24, a higher percentage of any patient population can be treated compared with addressing either MHC class I allele alone. While in most populations less than 50% of patients could be addressed by either allele alone, a vaccine comprising HLA-A*24 and HLA-A*02 epitopes can treat at least 60% of patients in any relevant population. Specifically, the following percentages of patients will be positive for at least one of these alleles in various regions: USA 61%, Western Europe 62%, China 75%, South Korea 77%, Japan 86% (calculated from www.allelefrequencies.net). 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 HLA alleles coverage in European Caucasian population  
               
               
                 (calculated from (Gragert et al., 2013)). 
               
            
           
           
               
               
               
               
               
            
               
                   
                 coverage 
                   
                   
                   
               
               
                   
                 (at least 
                   
                   
                 combined 
               
               
                   
                 one A- 
                 combined 
                 combined 
                 with B*07 
               
               
                   
                 allele) 
                 with B*07 
                 with B*44 
                 and B*44 
               
               
                   
               
               
                 A*02/A*01 
                 70% 
                 78% 
                 78% 
                 84% 
               
               
                 A*02/A*03 
                 68% 
                 76% 
                 76% 
                 83% 
               
               
                 A*02/A*24 
                 61% 
                 71% 
                 71% 
                 80% 
               
               
                 A*01/A*03 
                 52% 
                 64% 
                 65% 
                 75% 
               
               
                 A*01/A*24 
                 44% 
                 58% 
                 59% 
                 71% 
               
               
                 A*03/A*24 
                 40% 
                 55% 
                 56% 
                 69% 
               
               
                 A*02/A*01/A*03 
                 84% 
                 88% 
                 88% 
                 91% 
               
               
                 A*02/A*01/A*24 
                 79% 
                 84% 
                 84% 
                 89% 
               
               
                 A*02/A*03/A*24 
                 77% 
                 82% 
                 83% 
                 88% 
               
               
                 A*01/A*03/A*24 
                 63% 
                 72% 
                 73% 
                 81% 
               
               
                 A*02/A*01/A*03/ 
                 90% 
                 92% 
                 93% 
                 95% 
               
               
                 A*24 
               
               
                   
               
            
           
         
       
     
     In a preferred embodiment, the term “nucleotide sequence” refers to a heteropolymer of deoxyribonucleotides. 
     The nucleotide sequence coding for a particular peptide, oligopeptide, or polypeptide may be naturally occurring or they may be synthetically constructed. Generally, DNA segments encoding the peptides, polypeptides, and proteins of this invention are assembled from cDNA fragments and short oligonucleotide linkers, or from a series of oligonucleotides, to provide a synthetic gene that is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon. 
     As used herein the term “a nucleotide coding for (or encoding) a peptide” refers to a nucleotide sequence coding for the peptide including artificial (man-made) start and stop codons compatible for the biological system the sequence is to be expressed by, for example, a dendritic cell or another cell system useful for the production of TCRs. 
     As used herein, reference to a nucleic acid sequence includes both single stranded and double stranded nucleic acid. Thus, for example for DNA, the specific sequence, unless the context indicates otherwise, refers to the single strand DNA of such sequence, the duplex of such sequence with its complement (double stranded DNA) and the complement of such sequence. 
     The term “coding region” refers to that portion of a gene which either naturally or normally codes for the expression product of that gene in its natural genomic environment, i.e., the region coding in vivo for the native expression product of the gene. 
     The coding region can be derived from a non-mutated (“normal”), mutated or altered gene, or can even be derived from a DNA sequence, or gene, wholly synthesized in the laboratory using methods well known to those of skill in the art of DNA synthesis. 
     The term “expression product” means the polypeptide or protein that is the natural translation product of the gene and any nucleic acid sequence coding equivalents resulting from genetic code degeneracy and thus coding for the same amino acid(s). 
     The term “fragment”, when referring to a coding sequence, means a portion of DNA comprising less than the complete coding region, whose expression product retains essentially the same biological function or activity as the expression product of the complete 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, which has been derived from DNA isolated at least once in substantially pure form, i.e., free of contaminating endogenous materials and in a quantity or concentration enabling identification, manipulation, and recovery of the segment and its component nucleotide sequences by standard biochemical methods, for example, by using a cloning vector. Such segments are provided in the form of an open reading frame uninterrupted by internal non-translated sequences, or introns, which are typically present in eukaryotic genes. Sequences of non-translated DNA may be present downstream from the open reading frame, where the same do not interfere with manipulation or expression of the coding regions. 
     The term “primer” means a short nucleic acid sequence that can be paired with one strand of DNA and provides a free 3′-OH end at which a DNA polymerase starts synthesis of a deoxyribonucleotide chain. 
     The term “promoter” means a region of DNA involved in binding of RNA polymerase to initiate transcription. 
     The term “isolated” means that the material is removed from its original environment (e.g., the natural environment, if it is naturally occurring). For example, a naturally-occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or polypeptide, separated from some or all of the coexisting materials in the natural system, is isolated. Such polynucleotides could be part of a vector and/or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of its natural environment. 
     The polynucleotides, and recombinant or immunogenic polypeptides, disclosed in accordance with the present invention may also be in “purified” form. The term “purified” does not require absolute purity; rather, it is intended as a relative definition, and can include preparations that are highly purified or preparations that are only partially purified, as those terms are understood by those of skill in the relevant art. For example, individual clones isolated from a cDNA library have been conventionally purified to electrophoretic homogeneity. Purification of starting material or natural material to at least one order of magnitude, preferably two or three orders, and more preferably four or five orders of magnitude is expressly contemplated. Furthermore, a claimed polypeptide which has a purity of preferably 99.999%, or at least 99.99% or 99.9%; and even desirably 99% by weight or greater is expressly encompassed. 
     The nucleic acids and polypeptide expression products disclosed according to the present invention, as well as expression vectors containing such nucleic acids and/or such polypeptides, may be 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), advantageously 0.01%, by weight, preferably at least about 0.1% by weight. Enriched preparations of about 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 advantageously be in enriched or isolated form. The term “active fragment” means a fragment, usually of a peptide, polypeptide or nucleic acid sequence, that generates an immune response (i.e., has immunogenic activity) when administered, alone or optionally with a suitable adjuvant or in a vector, to an animal, such as a mammal, for example, a rabbit or a mouse, and also including a human, such immune response taking the form of stimulating a T-cell response within the recipient animal, such as a human. Alternatively, the “active fragment” may 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 forms a subset of a larger sequence. For example, if a polypeptide were subjected to treatment with any of the common endopeptidases, such as trypsin or chymotrypsin, the oligopeptides resulting from such treatment would represent portions, segments or fragments of the starting polypeptide. When used in relation to polynucleotides, these terms refer to the products produced by treatment of said polynucleotides with any of the endonucleases. 
     In accordance with the present invention, the term “percent identity” or “percent identical”, when referring to a sequence, means that a sequence is compared to a claimed or described sequence after alignment of the sequence to be compared (the “Compared Sequence”) with the described or claimed sequence (the “Reference Sequence”). The percent identity is then determined according to the following formula:
 
percent identity=100[1−( C/R )]
 
     wherein C is the number of differences between the Reference Sequence and the Compared Sequence over the length of alignment between the Reference Sequence and the Compared Sequence, wherein 
     (i) each base or amino acid in the Reference Sequence that does not have a corresponding 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 in the Reference Sequence that is different from an aligned base or amino acid in the Compared Sequence, 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 over the length of the alignment with the Compared Sequence with any gap created in the Reference Sequence also being counted as a base or amino acid. 
     If an alignment exists between the Compared Sequence and the Reference Sequence for which the percent identity as calculated above is about equal to or greater than a specified minimum Percent Identity, then the Compared Sequence has the specified minimum percent identity to the Reference Sequence even though alignments may exist in which the herein above calculated percent identity is less than the specified percent identity. 
     As mentioned above, the present invention thus provides a peptide comprising a sequence that is selected from the group of consisting of SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499 or a variant thereof which is 88% homologous to SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499, or a variant thereof that will induce T cells cross-reacting 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 elongated versions of said peptides to class II. 
     In the present invention, the term “homologous” refers to the degree of identity (see percent identity above) between sequences of two amino acid sequences, i.e. peptide or polypeptide sequences. The aforementioned “homology” is determined by comparing two sequences aligned under optimal conditions over the sequences to be compared. Such a sequence homology can be calculated by creating an alignment using, for example, the ClustalW algorithm. Commonly available sequence analysis software, more specifically, Vector NTI, GENETYX or other tools are provided by public databases. 
     A person skilled in the art will be able to assess, whether T cells induced by a variant of a specific peptide will be able to cross-react with the peptide itself (Appay et al., 2006; Colombetti et al., 2006; Fong et al., 2001; Zaremba et al., 1997). 
     By a “variant” of the given 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 replacing them with the side chain of another naturally occurring amino acid residue or some other side chain) such that the peptide is still able to bind to an HLA molecule in substantially the same way as a peptide consisting of the given amino acid sequence in consisting of SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499. For example, a peptide may be modified so that it at least maintains, if not improves, the ability to interact with and bind to the binding groove of a suitable MHC molecule, such as HLA-A*02 or -DR, and in that way, it at least maintains, if not improves, the ability to bind to the TCR of activated T cells. 
     These T cells can subsequently cross-react with cells and kill cells that express a polypeptide that contains the natural amino acid sequence of the cognate peptide as defined in the aspects of the invention. As can be derived from the scientific literature and databases (Godkin et al., 1997; Rammensee et al., 1999), certain positions of HLA binding peptides are typically anchor residues forming a core sequence fitting to the binding motif of the HLA receptor, which is defined by polar, electrophysical, hydrophobic and spatial properties of the polypeptide chains constituting the binding groove. Thus, one skilled in the art would be able to modify the amino acid sequences set forth in SEQ ID NO: 1 to SEQ ID NO 383 and SEQ ID NO: 448 to SEQ ID NO: 499, by maintaining the known anchor residues, and would be able to determine whether such variants maintain the ability to bind MHC class I or II molecules. The variants of the present invention retain the ability to bind to the TCR of activated T cells, which can subsequently cross-react with and kill cells that express a polypeptide containing the natural amino acid sequence of the cognate peptide as defined in the aspects of the invention. 
     The original (unmodified) peptides as disclosed herein can be modified by the substitution of one or more residues at different, possibly selective, sites within the peptide chain, if not otherwise stated. Preferably those substitutions are located at the end of the amino acid chain. Such substitutions may be of a conservative nature, for example, where one amino acid is replaced by an amino acid of similar structure and characteristics, such as where a hydrophobic amino acid is replaced by another hydrophobic amino acid. Even more conservative would be replacement of amino acids of the same or similar size and chemical nature, such as where leucine is replaced by isoleucine. In studies of sequence variations in families of naturally occurring homologous proteins, certain amino acid substitutions are more often tolerated than others, and these are often show correlation with similarities in size, charge, polarity, and hydrophobicity between the original amino acid and its replacement, and such is the basis for defining “conservative substitutions.” 
     Conservative substitutions are herein defined as exchanges within one of the following five groups: Group 1—small aliphatic, nonpolar or slightly polar residues (Ala, Ser, Thr, Pro, Gly); Group 2—polar, negatively charged residues and their amides (Asp, Asn, Glu, Gln); Group 3—polar, positively charged residues (His, Arg, Lys); Group 4—large, aliphatic, nonpolar residues (Met, Leu, Ile, Val, Cys); and Group 5—large, aromatic residues (Phe, Tyr, Trp). 
     In an aspect, conservative substitutions may include those, which are described by Dayhoff in “The Atlas of Protein Sequence and Structure. Vol. 5 ”, Natl. Biomedical Research , the contents of which are incorporated by reference in their entirety. For example, in an aspect, amino acids, which belong to one of the following groups, can be exchanged for one another, thus, constituting a conservative exchange: Group 1: alanine (A), proline (P), glycine (G), asparagine (N), serine (S), threonine (T); Group 2: cysteine (C), serine (S), tyrosine (Y), threonine (T); Group 3: valine (V), isoleucine (I), leucine (L), methionine (M), alanine (A), phenylalanine (F); Group 4: lysine (K), arginine (R), histidine (H); Group 5: phenylalanine (F), tyrosine (Y), tryptophan (W), histidine (H); and Group 6: aspartic acid (D), glutamic acid (E). In an aspect, a conservative amino acid substitution may be selected from the following of T→A, G→A, A→I, T→V, A→M, T→I, A→V, T→G, and/or T→S. 
     In an aspect, a conservative amino acid substitution may include the substitution of an amino acid by another amino acid of the same class, for example, (1) nonpolar: Ala, Val, Leu, Ile, Pro, Met, Phe, Trp; (2) uncharged polar: Gly, Ser, Thr, Cys, Tyr, Asn, Gln; (3) acidic: Asp, Glu; and (4) basic: Lys, Arg, His. Other conservative amino acid substitutions may also be made as follows: (1) aromatic: Phe, Tyr, His; (2) proton donor: Asn, Gln, Lys, Arg, His, Trp; and (3) proton acceptor: Glu, Asp, Thr, Ser, Tyr, Asn, Gln (see, for example, U.S. Pat. No. 10,106,805, the contents of which are incorporated by reference in their entirety). 
     In another aspect, conservative substitutions may be made in accordance with Table A. Methods for predicting tolerance to protein modification may be found in, for example, Guo et al.,  Proc. Natl. Acad. Sci., USA,  101(25):9205-9210 (2004), the contents of which are incorporated by reference in their entirety. 
     
       
         
           
               
             
               
                 TABLE A 
               
             
            
               
                   
               
               
                 Conservative Amino Acid Substitutions 
               
            
           
           
               
               
               
            
               
                   
                 Amino Acid 
                 Substitutions (others are known in the art) 
               
               
                   
                   
               
               
                   
                 Ala 
                 Ser, Gly, Cys 
               
               
                   
                 Arg 
                 Lys, Gln, His 
               
               
                   
                 Asn 
                 Gln, His, Glu, Asp 
               
               
                   
                 Asp 
                 Glu, Asn, Gln 
               
               
                   
                 Cys 
                 Ser, Met, Thr 
               
               
                   
                 Gln 
                 Asn, Lys, Glu, Asp, Arg 
               
               
                   
                 Glu 
                 Asp, Asn, Gln 
               
               
                   
                 Gly 
                 Pro, Ala, Ser 
               
               
                   
                 His 
                 Asn, Gln, Lys 
               
               
                   
                 Ile 
                 Leu, Val, Met, Ala 
               
               
                   
                 Leu 
                 Ile, Val, Met, Ala 
               
               
                   
                 Lys 
                 Arg, Gln, His 
               
               
                   
                 Met 
                 Leu, Ile, Val, Ala, Phe 
               
               
                   
                 Phe 
                 Met, Leu, Tyr, Trp, His 
               
               
                   
                 Ser 
                 Thr, Cys, Ala 
               
               
                   
                 Thr 
                 Ser, Val, Ala 
               
               
                   
                 Trp 
                 Tyr, Phe 
               
               
                   
                 Tyr 
                 Trp, Phe, His 
               
               
                   
                 Val 
                 Ile, Leu, Met, Ala, Thr 
               
               
                   
                   
               
            
           
         
       
     
     In another aspect, conservative substitutions may be those shown in Table B under the heading of “conservative substitutions.” If such substitutions result in a change in biological activity, then more substantial changes, denominated “exemplary substitutions” in Table B, may be introduced and the products screened if needed. 
     
       
         
           
               
             
               
                 TABLE B 
               
             
            
               
                   
               
               
                 Amino Acid Substitutions 
               
            
           
           
               
               
               
               
            
               
                   
                 Original Residue 
                   
                   
               
               
                   
                 (naturally 
                   
                   
               
               
                   
                 occurring amino 
                 Conservative 
                   
               
               
                   
                 acid) 
                 Substitutions 
                 Exemplary Substitutions 
               
               
                   
                   
               
               
                   
                 Ala (A) 
                 Val 
                 Val; Leu; Ile 
               
               
                   
                 Arg (R) 
                 Lys 
                 Lys; Gln; Asn 
               
               
                   
                 Asn (N) 
                 Gln 
                 Gln; His; Asp, Lys; Arg 
               
               
                   
                 Asp (D) 
                 Glu 
                 Glu; Asn 
               
               
                   
                 Cys (C) 
                 Ser 
                 Ser; Ala 
               
               
                   
                 Gln (Q) 
                 Asn 
                 Asn; Glu 
               
               
                   
                 Glu (E) 
                 Asp 
                 Asp; Gln 
               
               
                   
                 Gly (G) 
                 Ala 
                 Ala 
               
               
                   
                 His (H) 
                 Arg 
                 Asn; Gln; Lys; Arg 
               
               
                   
                 Ile (I) 
                 Leu 
                 Leu; Val; Met; Ala; Phe; 
               
               
                   
                   
                   
                 Norleucine 
               
               
                   
                 Leu (L) 
                 Ile 
                 Norleucine; Ile; Val; Met; 
               
               
                   
                   
                   
                 Ala; Phe 
               
               
                   
                 Lys (K) 
                 Arg 
                 Arg; Gln; Asn 
               
               
                   
                 Met (M) 
                 Leu 
                 Leu; Phe; He 
               
               
                   
                 Phe (F) 
                 Tyr 
                 Leu; Val; Ile; Ala; Tyr 
               
               
                   
                 Pro (P) 
                 Ala 
                 Ala 
               
               
                   
                 Ser (S) 
                 Thr 
                 Thr 
               
               
                   
                 Thr (T) 
                 Ser 
                 Ser 
               
               
                   
                 Trp ( W ) 
                 Tyr 
                 Tyr; Phe 
               
               
                   
                 Tyr (Y) 
                 Phe 
                 Trp; Phe; Thr; Ser 
               
               
                   
                 Val (V) 
                 Leu 
                 Ile; Leu; Met; Phe; Ala; 
               
               
                   
                   
                   
                 Norleucine 
               
               
                   
                   
               
            
           
         
       
     
     Less conservative substitutions might involve the replacement of one amino acid by another that has similar characteristics but is somewhat different in size, such as replacement of an alanine by an isoleucine residue. Highly non-conservative replacements might involve substituting an acidic amino acid for one that is polar, or even for one that is basic in character. Such “radical” substitutions cannot, however, be dismissed as potentially ineffective since chemical effects are not totally predictable and radical substitutions might well give rise to serendipitous effects not otherwise predictable from simple chemical principles. 
     Of course, such substitutions may involve structures other than the common L-amino acids. Thus, D-amino acids might be substituted for the L-amino acids commonly found in the antigenic peptides of the invention and yet still be encompassed by the disclosure herein. In addition, non-standard amino acids (i.e., other than the common naturally occurring proteinogenic amino acids) may also be used for substitution purposes to produce immunogens and immunogenic polypeptides according to 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 those substitutions will be tested to determine if the combined substitutions result in additive or synergistic effects on the antigenicity of the peptide. At most, no more than four positions within the peptide would be simultaneously substituted. 
     A peptide consisting essentially of the amino acid sequence as indicated herein can have one or two non-anchor amino acids (see below regarding the anchor motif) exchanged without that the ability to bind to a molecule of the human major histocompatibility complex (MHC) class-I or -II is substantially changed or is negatively affected, when compared to the non-modified peptide. In another embodiment, in a peptide consisting essentially of the amino acid sequence as indicated herein, one or two amino acids can be exchanged with their conservative exchange partners (see herein below) without that the ability to bind to a molecule of the human major histocompatibility complex (MHC) class-I or -II is substantially changed, or is negatively affected, when compared to the non-modified peptide. 
     The amino acid residues that do not substantially contribute to interactions with the T-cell receptor can be modified by replacement with other amino acid whose incorporation does not substantially affect T-cell reactivity and does not eliminate binding to the relevant MHC. Thus, apart from the proviso given, the peptide of the invention may be any peptide (by which term the inventors include oligopeptide or polypeptide), which includes the amino acid sequences, or a portion or variant thereof as given. 
     Most preferred are peptides consisting of the sequences as given. 
     
       
         
           
               
             
               
                 TABLE 6 
               
               
                   
               
               
                 Variants and motif of the 
               
               
                 peptides according to 
               
               
                 SEQ ID NO: 13, 25, 38, 54 and 362 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Position 
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
                 7 
                 8 
                 9 
                 10 
                   
               
               
                   
               
               
                 Seq ID No 13 
                 L 
                 P 
                 N 
                 T 
                 G 
                 R 
                 I 
                 G 
                 Q 
                 L 
                   
               
               
                 Variant 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 F 
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 V 
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 M 
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 I 
               
               
                   
               
               
                 Position 
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
                 7 
                 8 
                 9 
               
               
                   
               
               
                 Seq ID No 25 
                 R 
                 P 
                 Q 
                 G 
                 A 
                 V 
                 G 
                 G 
                 L 
                   
                   
               
               
                 Variant 
                   
                   
                   
                   
                   
                   
                   
                   
                 F 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 V 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 M 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 A 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 I 
               
               
                   
               
               
                 Position 
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
                 7 
                 8 
                 9 
                 10 
               
               
                   
               
               
                 Seq ID No 38 
                 R 
                 P 
                 S 
                 F 
                 P 
                 N 
                 L 
                 T 
                 S 
                 F 
                   
               
               
                 Variant 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 L 
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 V 
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 M 
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 A 
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 I 
               
               
                   
               
               
                 Position 
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
                 7 
                 8 
                 9 
                 10 
                 11 
               
               
                   
               
               
                 Seq ID No 54 
                 V 
                 P 
                 S 
                 C 
                 G 
                 R 
                 S 
                 V 
                 E 
                 G 
                 L 
               
               
                 Variant 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 F 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 V 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 M 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 A 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 I 
               
               
                   
               
               
                 Position 
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
                 7 
                 8 
                 9 
               
               
                   
               
               
                 Seq ID No 362 
                 K 
                 P 
                 M 
                 L 
                 P 
                 P 
                 A 
                 A 
                 F 
                   
                   
               
               
                 Variant 
                   
                   
                   
                   
                   
                   
                   
                   
                 L 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 V 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 M 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 A 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 I 
               
               
                   
               
            
           
         
       
     
     Longer (elongated) peptides may also be suitable. It is possible that MHC class I epitopes, although usually between 8 and 11 amino acids long, are generated by peptide processing from longer peptides or proteins that include the actual epitope. It is preferred that the residues that flank the actual epitope are residues that do not substantially affect proteolytic cleavage necessary to expose the actual epitope during processing. 
     The peptides of the invention can be elongated by up to four amino acids, that is 1, 2, 3 or 4 amino acids can be added to either end in any combination between 4:0 and 0:4. Combinations of the elongations according to the invention can be found in Table 7. 
     
       
         
           
               
             
               
                 TABLE 7 
               
               
                   
               
               
                 Combinations of the elongations of peptides of the invention 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                 C-terminus 
                 N-terminus 
               
               
                   
                   
               
               
                   
                 4 
                 0 
               
               
                   
                 3 
                 0 or 1 
               
               
                   
                   
               
               
                   
                 C-terminus 
                 N-terminus 
               
               
                   
                   
               
               
                   
                 2 
                 0 or 1 or 2 
               
               
                   
                 1 
                 0 or 1 or 2 or 3 
               
               
                   
                 0 
                 0 or 1 or 2 or 3 or 4 
               
               
                   
                   
               
               
                   
                 N-terminus 
                 C-terminus 
               
               
                   
                   
               
               
                   
                 4 
                 0 
               
               
                   
                 3 
                 0 or 1 
               
               
                   
                 2 
                 0 or 1 or 2 
               
               
                   
                 1 
                 0 or 1 or 2 or 3 
               
               
                   
                 0 
                 0 or 1 or 2 or 3 or 4 
               
               
                   
                   
               
            
           
         
       
     
     The amino acids for the elongation/extension can be the peptides of the original sequence of the protein or any other amino acid(s). The elongation can be used to enhance the stability or solubility of the peptides. 
     Thus, the epitopes of the present invention may be identical to naturally occurring tumor-associated or tumor-specific epitopes or may include epitopes that differ by no more than four residues from the reference peptide, as long as they have substantially identical antigenic activity. 
     In an alternative embodiment, the peptide is elongated on either or both sides by more than 4 amino acids, preferably to a total length of up to 30 amino acids. This may lead to MHC class II binding peptides. Binding to MHC class II can be tested by methods known in the art. 
     Accordingly, the present invention provides peptides and variants of MHC class I epitopes, wherein the peptide or variant has an overall length of between 8 and 100, preferably between 8 and 30, and most preferred between 8 and 14, namely 8, 9, 10, 11, 12, 13, 14 amino acids, in case of the elongated class II binding peptides the length 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 molecule of the human major histocompatibility complex (MHC) class I or II. Binding of a peptide or a variant to an MHC complex may be tested by methods known in the art. 
     Preferably, when the T cells specific for a peptide according to the present invention are tested against the substituted peptides, the peptide concentration at which the substituted peptides achieve half the maximal increase in lysis relative to background is no more than about 1 mM, preferably no more than about 1 μM, more preferably no more than about 1 nM, and still more preferably no more than about 100 pM, and most preferably no more than about 10 pM. It is also preferred that the substituted peptide be recognized by T cells from more than one individual, at least two, and more preferably three individuals. 
     In a particularly 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: 383 and SEQ ID NO: 448 to SEQ ID NO: 499. 
     “Consisting essentially of” shall mean 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 383 and SEQ ID NO: 448 to SEQ ID NO: 499 or a variant thereof contains additional N- and/or C-terminally located stretches of amino acids that are not necessarily forming part of the peptide that functions as an epitope for MHC molecules epitope. 
     Nevertheless, these stretches can be important to provide an efficient introduction of the peptide according to the present invention into the cells. In one embodiment of the present invention, the peptide is part of a fusion protein which comprises, for example, the 80 N-terminal amino acids of the HLA-DR antigen-associated invariant chain (p33, in the following “Ii”) as derived from the NCBI, GenBank Accession number X00497. In other fusions, the peptides of the present invention can be fused to an antibody as described herein, or a functional part thereof, in particular into a sequence of an antibody, so as to be specifically targeted by said antibody, or, for example, to or into an antibody that is specific for dendritic cells as described herein. 
     In addition, the peptide or variant may be modified further to improve stability and/or binding to MHC molecules in order to elicit a stronger immune response. Methods for such an optimization of a peptide sequence are well known in the art and include, for example, the introduction of reverse peptide bonds or non-peptide bonds. 
     In a reverse peptide bond amino acid residues are not joined by peptide (—CO—NH—) linkages, but the peptide bond is reversed. Such retro-inverso peptidomimetics may be made using methods known in the art, for example such as those described in Meziere et al (1997) (Meziere et al., 1997), incorporated herein by reference. This approach involves making pseudopeptides containing changes involving the backbone, and not the orientation of side chains. Meziere et al. (Meziere et al., 1997) show that for MHC binding and T helper cell responses, these pseudopeptides are useful. Retro-inverse peptides, which contain NH—CO bonds instead of CO—NH peptide bonds, are much more resistant to proteolysis. 
     A non-peptide bond is, for example, —CH 2 —NH, —CH 2 S—, —CH 2 CH 2 —, —CH═CH—, —COCH 2 —, —CH(OH)CH 2 —, and —CH 2 SO—. U.S. Pat. No. 4,897,445 provides a method for the solid phase synthesis of non-peptide bonds (—CH 2 —NH) in polypeptide chains which involves polypeptides synthesized by standard procedures and the non-peptide bond synthesized by reacting an amino aldehyde and an amino acid in the presence of NaCNBH 3 . 
     Peptides comprising the sequences described above may be synthesized with additional chemical groups present at their amino and/or carboxy termini, to enhance the stability, bioavailability, and/or affinity of the peptides. For example, hydrophobic groups such as carbobenzoxyl, dansyl, or t-butyloxycarbonyl groups may be added to the peptides&#39; amino termini. Likewise, an acetyl group or a 9-fluorenylmethoxy-carbonyl group may be placed at the peptides&#39; amino termini. Additionally, the hydrophobic group, t-butyloxycarbonyl, or an amido group may be added to the peptides&#39; carboxy termini. 
     Further, the peptides of the invention may 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, rather than the usual L-isomer. Still further, at least one of the amino acid residues of the peptides of the invention may be substituted by one of the well-known non-naturally occurring amino acid residues. Alterations such as these may serve to increase the stability, bioavailability and/or binding action of the peptides of the invention. 
     Similarly, a peptide or variant of the invention may be modified chemically by reacting specific amino acids either before or after synthesis of the peptide. Examples for such modifications are well known in the art and are summarized e.g. in R. Lundblad, Chemical Reagents for Protein Modification, 3rd ed. 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 2,4,6-trinitrobenzene sulphonic acid (TNBS), amide modification of carboxyl groups and sulphydryl modification by performic acid oxidation of cysteine to cysteic acid, formation of mercurial derivatives, formation of mixed disulphides with other thiol compounds, reaction with maleimide, carboxymethylation with iodoacetic acid or iodoacetamide and carbamoylation with cyanate at alkaline pH, although without limitation thereto. In this regard, the skilled person is referred to Chapter 15 of Current Protocols In Protein Science, Eds. Coligan et al. (John Wiley and Sons NY 1995-2000) (Coligan et al., 1995) for more extensive methodology relating to chemical modification of proteins. 
     Briefly, modification of e.g. arginyl residues in proteins is often based on the reaction of vicinal dicarbonyl compounds such as phenylglyoxal, 2,3-butanedione, and 1,2-cyclohexanedione to form an adduct. Another example is the reaction of methylglyoxal with arginine residues. Cysteine can be modified without concomitant modification of other nucleophilic sites such as lysine and histidine. As a result, a large number of reagents are available for the modification of cysteine. The websites of companies such as Sigma-Aldrich (http://www.sigma-aldrich.com) provide information on specific reagents. 
     Selective reduction of disulfide bonds in proteins is also common. Disulfide bonds can be formed and oxidized during the heat treatment of biopharmaceuticals. Woodward&#39;s Reagent K may be used to modify specific glutamic acid residues. N-(3-(dimethylamino)propyl)-N′-ethylcarbodiimide can be used to form intra-molecular crosslinks between a lysine residue and a glutamic acid residue. For example, diethylpyrocarbonate is a reagent for the modification of histidyl residues in proteins. Histidine can also be modified using 4-hydroxy-2-nonenal. The reaction of lysine residues and other α-amino groups is, for example, useful in binding of peptides to surfaces or the cross-linking of proteins/peptides. Lysine is the site of attachment of poly(ethylene)glycol and the major site of modification in the glycosylation of proteins. Methionine residues in proteins can be modified with e.g. iodoacetamide, bromoethylamine, and chloramine T. 
     Tetranitromethane and N-acetylimidazole can be used for the modification of tyrosyl residues. Cross-linking via the formation of dityrosine can be accomplished with hydrogen peroxide/copper ions. 
     Recent studies on the modification of tryptophan have used N-bromosuccinimide, 2-hydroxy-5-nitrobenzyl bromide or 3-bromo-3-methyl-2-(2-nitrophenylmercapto)-3H-indole (BPNS-skatole). 
     Successful modification of therapeutic proteins and peptides with PEG is often associated with an extension of circulatory half-life while cross-linking of proteins with glutaraldehyde, polyethylene glycol diacrylate and formaldehyde is used for the preparation of hydrogels. Chemical modification of allergens for immunotherapy is often achieved by carbamylation with potassium cyanate. 
     A peptide or variant, wherein the peptide is modified or includes non-peptide bonds is a preferred embodiment of the invention. 
     Another embodiment of the present invention relates to a non-naturally occurring peptide wherein said peptide consists or consists essentially of an amino acid sequence according to SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499 and has been synthetically produced (e.g. synthesized) as a pharmaceutically acceptable salt. Methods to synthetically produce peptides are well known in the art. The salts of the peptides according to the present invention differ substantially from the peptides in their state(s) in vivo, as the peptides as generated in vivo are no salts. The non-natural salt form of the peptide mediates the solubility of the peptide, in particular in the context of pharmaceutical compositions comprising the peptides, e.g. the peptide vaccines as disclosed herein. A sufficient and at least substantial solubility of the peptide(s) is required in order to efficiently provide the peptides to the subject to be treated. Preferably, the salts are pharmaceutically acceptable salts of the peptides. These salts according to the invention include alkaline and earth alkaline salts such as salts of the Hofmeister series comprising as anions PO 4   3− , SO 4   2− , CH 3 COO − , Cl − , Br − , NO 3   − , ClO 4   − , I − , SCN −  and as cations NH 4   + , Rb + , K + , Na + , Cs + , Li + , Zn 2+ , Mg 2+ , Ca 2+ , Mn 2+ , Cu 2+  and Ba 2+ . Particularly salts are selected from (NH 4 ) 3 PO 4 , (NH 4 ) 2 HPO 4 , (NH 4 )H 2 PO 4 , (NH 4 ) 2 SO 4 , NH 4 CH 3 COO, NH 4 Cl, NH 4 Br, NH 4 NO 3 , NH 4 ClO 4 , NH 4 I, NH 4 SCN, Rb 3 PO 4 , Rb 2 HPO 4 , RbH 2 PO 4 , Rb 2 SO 4 , Rb 4 CH 3 COO, Rb 4 Cl, Rb 4 Br, Rb 4 NO 3 , Rb 4 ClO 4 , Rb 4 I, Rb 4 SCN, K 3 PO 4 , K 2 HPO 4 , KH 2 PO 4 , K 2 SO 4 , KCH 3 COO, KCl, KBr, KNOB, KClO 4 , KI, KSCN, Na 3 PO 4 , Na 2 HPO 4 , NaH 2 PO 4 , Na 2 SO 4 , NaCH 3 COO, NaCl, NaBr, NaNO 3 , NaClO 4 , NaI, NaSCN, ZnCl 2  Cs 3 PO 4 , Cs 2 HPO 4 , CsH 2 PO 4 , Cs 2 SO 4 , CsCH 3 COO, CsCl, CsBr, CsNO 3 , CsClO 4 , CsI, CsSCN, Li 3 PO 4 , Li 2 HPO 4 , LiH 2 PO 4 , Li 2 SO 4 , LiCH 3 COO, LiCl, LiBr, LiNO 3 , LiClO 4 , LiI, LiSCN, Cu 2 SO 4 , Mg 3 (PO 4 ) 2 , Mg 2 HPO 4 , Mg(H 2 PO 4 ) 2 , Mg 2 SO 4 , Mg(CH 3 COO) 2 , MgCl 2 , MgBr 2 , Mg(NO 3 ) 2 , Mg(ClO 4 ) 2 , MgI 2 , Mg(SCN) 2 , MnCl 2 , Ca 3 (PO 4 ), Ca 2 HPO 4 , Ca(H 2 PO 4 ) 2 , CaSO 4 , Ca(CH 3 COO) 2 , CaCl 2 ), CaBr 2 , Ca(NO 3 ) 2 , Ca(ClO 4 ) 2 , CaI 2 , Ca(SCN) 2 , Ba 3 (PO 4 ) 2 , Ba 2 HPO 4 , Ba(H 2 PO 4 ) 2 , BaSO 4 , Ba(CH 3 COO) 2 , BaCl 2 , BaBr 2 , Ba(NO 3 ) 2 , Ba(ClO 4 ) 2 , BaI 2 , and Ba(SCN) 2 . Particularly preferred are NH acetate, MgCl 2 , KH 2 PO 4 , Na 2 SO 4 , KCl, NaCl, and CaCl 2 ), such as, for example, the chloride or acetate (trifluoroacetate) salts. 
     In a preferred embodiment, the pharmaceutical compositions comprise the peptides as salts of acetic acid (acetates), trifluoro acetates or hydrochloric acid (chlorides). 
     In an aspect, a polypeptide described herein is in the form of a pharmaceutically acceptable salt. 
     In another aspect, a polypeptide in the form of a pharmaceutical salt is in crystalline form. 
     In an aspect, a pharmaceutically acceptable salt described herein refers to salts which possess toxicity profiles within a range that is acceptable for pharmaceutical applications. 
     In an aspect, pharmaceutically acceptable salts may increase the solubility and/or stability of peptides of described herein. In another aspect, pharmaceutical salts described herein may be prepared by conventional means from the corresponding carrier peptide or complex by reacting, for example, the appropriate acid or base with peptides or complexes as described herein. 
     In another aspect, the pharmaceutically acceptable salts are in crystalline form or semi-crystalline form. 
     In yet another aspect, pharmaceutically acceptable salts may include, for example, those described in Handbook of Pharmaceutical Salts: Properties, Selection, and Use By P. H. Stahl and C. G. Wermuth (Wiley-VCH 2002) and L. D. Bighley, S. M. Berge, D. C. Monkhouse, in “Encyclopedia of Pharmaceutical Technology”. Eds. J. Swarbrick and J. C. Boylan, Vol. 13, Marcel Dekker, Inc., New York, Basel, Hong Kong 1995, pp. 453-499, each of these references is herein incorporated by reference in their entirety. 
     Generally, peptides and variants (at least those containing peptide linkages between amino acid residues) may be synthesized by the Fmoc-polyamide mode of solid-phase peptide synthesis as disclosed by Lukas et al. (Lukas et al., 1981) and by references as cited therein. Temporary N-amino group protection is afforded by the 9-fluorenylmethyloxycarbonyl (Fmoc) group. Repetitive cleavage of this highly base-labile protecting group is done using 20% piperidine in N, N-dimethylformamide. Side-chain functionalities may be protected as their butyl ethers (in the case of serine threonine and tyrosine), butyl esters (in the case of glutamic acid and aspartic acid), butyloxycarbonyl derivative (in the case of lysine and histidine), trityl derivative (in the case of cysteine) and 4-methoxy-2,3,6-trimethylbenzenesulphonyl derivative (in the case of arginine). Where glutamine or asparagine are C-terminal residues, use is made of the 4,4′-dimethoxybenzhydryl group for protection of the side chain amido functionalities. The solid-phase support is based on a polydimethyl-acrylamide polymer constituted from the three monomers dimethylacrylamide (backbone-monomer), bisacryloylethylene diamine (cross linker) and acryloylsarcosine methyl ester (functionalizing agent). The peptide-to-resin cleavable linked agent used is the acid-labile 4-hydroxymethyl-phenoxyacetic acid derivative. All amino acid derivatives are added as their preformed symmetrical anhydride derivatives with the exception of asparagine and glutamine, which are added using a reversed N, N-dicyclohexyl-carbodiimide/1hydroxybenzotriazole mediated coupling procedure. All coupling and deprotection reactions are monitored using ninhydrin, trinitrobenzene sulphonic acid or isotin test procedures. Upon completion of synthesis, peptides are cleaved from the resin support with concomitant removal of side-chain protecting groups by treatment with 95% trifluoroacetic acid containing a 50% scavenger mix. Scavengers commonly used include ethanedithiol, phenol, anisole and water, the exact choice depending on the constituent amino acids of the peptide being synthesized. Also a combination of solid phase and solution phase methodologies for the synthesis of peptides is possible (see, for example, (Bruckdorfer et al., 2004), and the references as cited therein). 
     Trifluoroacetic acid is removed by evaporation in vacuo, with subsequent trituration with diethyl ether affording the crude peptide. Any scavengers present are removed by a simple extraction procedure which on lyophilization of the aqueous phase affords the crude peptide free of scavengers. Reagents for peptide synthesis are generally available from e.g. Calbiochem-Novabiochem (Nottingham, UK). 
     Purification may be performed by anyone, or a combination of, techniques such as re-crystallization, size exclusion chromatography, ion-exchange chromatography, hydrophobic interaction chromatography and (usually) reverse-phase high performance liquid chromatography using e.g. acetonitrile/water gradient separation. 
     Analysis of peptides may be carried out using thin layer chromatography, electrophoresis, in particular capillary electrophoresis, solid phase extraction (CSPE), reverse-phase high performance liquid chromatography, amino-acid analysis after acid hydrolysis and by fast atom bombardment (FAB) mass spectrometric analysis, as well as MALDI and ESI-Q-TOF mass spectrometric analysis. 
     In order to select over-presented peptides, a presentation profile is calculated showing the median sample presentation as well as replicate variation. The profile juxtaposes samples of the tumor entity of interest to a baseline of normal tissue samples. Each of these profiles can then be consolidated into an over-presentation score by calculating the p-value of a Linear Mixed-Effects Model (Pinheiro et al., 2015) adjusting for multiple testing by False Discovery Rate (Benjamini and Hochberg, 1995) (cf. Example 1,  FIGS.  1 A- 1 I ). 
     For the identification and relative quantitation of HLA ligands by mass spectrometry, HLA molecules from shock-frozen tissue samples were purified and HLA-associated peptides were isolated. The isolated peptides were separated, and sequences were identified by online nano-electrospray-ionization (nanoESI) liquid chromatography-mass spectrometry (LC-MS) experiments. The resulting peptide sequences were verified by comparison of the fragmentation pattern of natural tumor-associated peptides (TUMAPs) recorded from acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer samples (N=149 samples) with the fragmentation patterns of corresponding synthetic reference peptides of identical sequences. Since the peptides were directly identified as ligands of HLA molecules of primary tumors, these results provide direct evidence for the natural processing and presentation of the identified peptides on primary cancer tissue obtained from 149 acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer patients. 
     The discovery pipeline XPRESIDENT® v2.1 (see, for example, US 2013-0096016, which is hereby incorporated by reference in its entirety) allows the identification and selection of relevant over-presented peptide vaccine candidates based on direct relative quantitation of HLA-restricted peptide levels on cancer tissues in comparison to several different non-cancerous tissues and organs. This was achieved by the development of label-free differential quantitation using the acquired LC-MS data processed by a proprietary data analysis pipeline, combining algorithms for sequence identification, spectral clustering, ion counting, retention time alignment, charge state deconvolution and normalization. 
     Presentation levels including error estimates for each peptide and sample were established. Peptides exclusively presented on tumor tissue and peptides over-presented in tumor versus non-cancerous tissues and organs have been identified. 
     HLA-peptide complexes from acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer tissue samples were purified and HLA-associated peptides were isolated and analyzed by LC-MS (see example 1). All TUMAPs contained in the present application were identified with this approach on acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer samples confirming their presentation on acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer. 
     TUMAPs identified on multiple acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer and normal tissues were quantified using ion-counting of label-free LC-MS data. The method assumes that LC-MS signal areas of a peptide correlate with its abundance in the sample. All quantitative signals of a peptide in various LC-MS experiments were normalized based on central tendency, averaged per sample and merged into a bar plot, called presentation profile. The presentation profile consolidates different analysis methods like protein database search, spectral clustering, charge state deconvolution (decharging) and retention time alignment and normalization. 
     Besides over-presentation of the peptide, mRNA expression of the underlying gene was tested. mRNA data were obtained via RNASeq analyses of normal tissues and cancer tissues (cf. Example 2,  FIGS.  2 A- 2 T ). An additional source of normal tissue data was a database of publicly available RNA expression data from around 3000 normal tissue samples (Lonsdale, 2013). Peptides which are derived from proteins whose coding mRNA is highly expressed in cancer tissue, but very low or absent in vital normal tissues, were preferably included in the present invention. 
     The present invention provides peptides that are useful in treating cancers/tumors, preferably acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer that over- or exclusively present the peptides of the invention. These peptides were shown by mass spectrometry to be naturally presented by HLA molecules on primary human acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer samples. 
     Many of the source gene/proteins (also designated “full-length proteins” or “underlying proteins”) from which the peptides are derived were shown to be highly over-expressed in cancer compared with normal tissues—“normal tissues” in relation to this invention shall mean either healthy blood cells, blood vessels, brain, heart, liver, lung, adrenal gland, bile duct, bladder, bone marrow, esophagus, gallbladder, large intestine, small intestine, kidney, lymph node, peripheral nerve, pancreas, pituitary, skin, spinal cord, spleen, stomach, thyroid, trachea cells or other normal tissue cells, demonstrating a high degree of tumor association of the source genes (see Example 2). Moreover, the peptides themselves are strongly over-presented on tumor tissue—“tumor tissue” in relation to this invention shall mean a sample from a patient suffering from acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer, but not on normal tissues (see Example 1). 
     HLA-bound peptides can be recognized by the immune system, specifically T lymphocytes. T cells can destroy the cells presenting the recognized HLA/peptide complex, e.g. acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer cells presenting the derived peptides. 
     The peptides of the present invention have been shown to be capable of stimulating T cell responses and/or are over-presented and thus can be used for the production of antibodies and/or TCRs, such as soluble TCRs, according to the present invention (see Example 3, Example 4). Furthermore, the peptides when complexed with the respective MHC can be used for the production of antibodies and/or TCRs, in particular sTCRs, according to the present invention, as well. Respective methods are well known to the person of skill and can be found in the respective literature as well (see also below). Thus, the peptides of the present invention are useful for generating an immune response in a patient by which tumor cells can be destroyed. An immune response in a patient can be induced by direct administration of the described peptides or suitable precursor substances (e.g. elongated peptides, proteins, or nucleic acids encoding these peptides) to the patient, ideally in combination with an agent enhancing the immunogenicity (i.e. an adjuvant). The immune response originating from such a therapeutic vaccination can be expected to be highly specific against tumor cells because the target peptides of the present invention are not presented on normal tissues in comparable copy numbers, preventing the risk of undesired autoimmune reactions against normal cells in the patient. 
     The present description further relates to T-cell receptors (TCRs) comprising an alpha chain and a beta chain (“alpha/beta TCRs”). Also provided are peptides according to the invention capable of binding to TCRs and antibodies when presented by an MHC molecule. 
     The present description also relates to fragments of the TCRs according to the invention that are capable of binding to a peptide antigen according to the present invention when presented by an HLA molecule. The term particularly relates to soluble TCR fragments, for example TCRs missing the transmembrane parts and/or constant regions, single chain TCRs, and fusions thereof to, for example, with Ig. 
     The present description also relates to nucleic acids, vectors and host cells for expressing TCRs and peptides of the present description; and methods of using the same. 
     The term “T-cell receptor” (abbreviated TCR) refers to a heterodimeric molecule comprising an alpha polypeptide chain (alpha chain) and a beta polypeptide chain (beta chain), wherein the heterodimeric receptor is capable of binding to a peptide antigen presented by an HLA molecule. The term also includes so-called gamma/delta TCRs. 
     In one embodiment the description provides a method of producing a TCR as described herein, the method comprising culturing a host cell capable of expressing the TCR under conditions suitable to promote expression of the TCR. 
     The description in another aspect relates to methods according to the description, wherein the antigen is loaded onto class I or II MHC molecules expressed on the surface of a suitable antigen-presenting cell or artificial antigen-presenting cell by contacting a sufficient amount of the antigen with an antigen-presenting cell or the antigen is loaded onto class I or II MHC tetramers by tetramerizing the antigen/class I or II MHC complex monomers. 
     The alpha and beta chains of alpha/beta TCR&#39;s, and the gamma and delta chains of gamma/delta TCRs, are generally regarded as each having two “domains”, namely variable and constant domains. The variable domain consists of a concatenation of variable region (V) and joining region (J). The variable domain may also include a leader region (L). Beta and delta chains may also include a diversity region (D). The alpha and beta constant domains may also include C-terminal transmembrane (TM) domains that anchor the alpha and beta chains to the cell membrane. 
     With respect to gamma/delta TCRs, the term “TCR gamma variable domain” as used herein refers to the concatenation of the TCR gamma V (TRGV) region without leader region (L), and the TCR gamma J (TRGJ) region, and the term TCR gamma constant domain refers to the extracellular TRGC region, or to a C-terminal truncated TRGC sequence. Likewise the term “TCR delta variable domain” refers to the concatenation of the TCR delta V (TRDV) region without leader region (L) and the TCR delta D/J (TRDD/TRDJ) region, and the term “TCR delta constant domain” refers to the extracellular TRDC region, or to a C-terminal truncated TRDC sequence. 
     TCRs of the present description preferably bind to a peptide-HLA molecule complex with a binding affinity (KD) of about 100 μM or less, about 50 μM or less, about 25 μM or less, or about 10 μM or less. More preferred are high affinity TCRs having binding affinities of about 1 μM or less, about 100 nM or less, about 50 nM or less, about 25 nM or less. Non-limiting examples of preferred binding affinity ranges for TCRs of the present invention include about 1 nM to about 10 nM; about 10 nM to about 20 nM; about 20 nM to about 30 nM; about 30 nM to about 40 nM; about 40 nM to about 50 nM; about 50 nM to about 60 nM; about 60 nM to about 70 nM; about 70 nM to about 80 nM; about 80 nM to about 90 nM; and about 90 nM to about 100 nM. 
     As used herein in connect with TCRs of the present description, “specific binding” and grammatical variants thereof are used to mean a TCR having a binding affinity (KD) for a peptide-HLA molecule complex of 100 μM or less. 
     Alpha/beta heterodimeric TCRs of the present description may have an introduced disulfide bond between their constant domains. Preferred TCRs of this type include those which have a TRAC constant domain sequence and a TRBC1 or TRBC2 constant domain sequence except that Thr 48 of TRAC and Ser 57 of TRBC1 or TRBC2 are replaced by cysteine residues, the said cysteines forming a disulfide bond between the TRAC constant domain sequence and the TRBC1 or TRBC2 constant domain sequence of the TCR. 
     With or without the introduced inter-chain bond mentioned above, alpha/beta hetero-dimeric TCRs of the present description may have a TRAC constant domain sequence and a TRBC1 or TRBC2 constant domain sequence, and the TRAC constant domain sequence and the TRBC1 or TRBC2 constant domain sequence of the TCR may be linked by the native disulfide bond between Cys4 of exon 2 of TRAC and Cys2 of exon 2 of TRBC1 or TRBC2. 
     TCRs of the present description may comprise a detectable label selected from the group consisting of a radionuclide, a fluorophore and biotin. TCRs of the present description may be conjugated to a therapeutically active agent, such as a radionuclide, a chemotherapeutic agent, or a toxin. 
     In an embodiment, a TCR of the present description having at least one mutation in the alpha chain and/or having at least one mutation in the beta chain has modified glycosylation compared to the unmutated TCR. 
     In an embodiment, a TCR comprising at least one mutation in the TCR alpha chain and/or TCR beta chain has a binding affinity for, and/or a binding half-life for, a peptide-HLA molecule complex, which is at least double that of a TCR comprising the unmutated TCR alpha chain and/or unmutated TCR beta chain. Affinity-enhancement of tumor-specific TCRs, and its exploitation, relies on the existence of a window for optimal TCR affinities. The existence of such a window is based on observations that TCRs specific for HLA-B*07-restricted pathogens have KD values that are generally about 10-fold lower when compared to TCRs specific for HLA-B*07-restricted tumor-associated self-antigens. It is now known, although tumor antigens have the potential to be immunogenic, because tumors arise from the individual&#39;s own cells only mutated proteins or proteins with altered translational processing will be seen as foreign by the immune system. Antigens that are upregulated or overexpressed (so called self-antigens) will not necessarily induce a functional immune response against the tumor: T-cells expressing TCRs that are highly reactive to these antigens will have been negatively selected within the thymus in a process known as central tolerance, meaning that only T-cells with low-affinity TCRs for self-antigens remain. Therefore, affinity of TCRs or variants of the present description to peptides can be enhanced by methods well known in the art. 
     The present description further relates to a method of identifying and isolating a TCR according to the present description, said method comprising incubating PBMCs from HLA-B*07-negative healthy donors with B*07/peptide monomers, incubating the PBMCs with tetramer-phycoerythrin (PE) and isolating the high avidity T-cells by fluorescence activated cell sorting (FACS)-Calibur analysis. 
     The present description further relates to a method of identifying and isolating a TCR according to the present description, said method comprising obtaining a transgenic mouse with the entire human TCRαβ gene loci (1.1 and 0.7 Mb), whose T-cells express a diverse human TCR repertoire that compensates for mouse TCR deficiency, immunizing the mouse with a peptide, incubating PBMCs obtained from the transgenic mice with tetramer-phycoerythrin (PE), and isolating the high avidity T-cells by fluorescence activated cell sorting (FACS)-Calibur analysis. 
     In one aspect, to obtain T-cells expressing TCRs of the present description, nucleic acids encoding TCR-alpha and/or TCR-beta chains of the present description are cloned into expression vectors, such as gamma retrovirus or lentivirus. The recombinant viruses are generated and then tested for functionality, such as antigen specificity and functional avidity. An aliquot of the final product is then used to transduce the target T-cell population (generally purified from patient PBMCs), which is expanded before infusion into the patient. 
     In another aspect, to obtain T-cells expressing TCRs of the present description, TCR RNAs are synthesized by techniques known in the art, e.g., in vitro transcription systems. The in vitro-synthesized TCR RNAs are then introduced into primary CD8+ T-cells obtained from healthy donors by electroporation to re-express tumor specific TCR-alpha and/or TCR-beta chains. 
     To increase the expression, nucleic acids encoding TCRs of the present description may be operably linked to strong promoters, such as retroviral long terminal repeats (LTRs), cytomegalovirus (CMV), murine stem cell virus (MSCV) U3, phosphoglycerate kinase (PGK), β-actin, ubiquitin, and a simian virus 40 (SV40)/CD43 composite promoter, elongation factor (EF)-1a and the spleen focus-forming virus (SFFV) promoter. In a preferred embodiment, the promoter is heterologous to the nucleic acid being expressed. 
     In addition to strong promoters, TCR expression cassettes of the present description may contain additional elements that can enhance transgene expression, including a central polypurine tract (cPPT), which promotes the nuclear translocation of lentiviral constructs (Follenzi et al., 2000), and the woodchuck hepatitis virus posttranscriptional regulatory element (wPRE), which increases the level of transgene expression by increasing RNA stability (Zufferey et al., 1999). 
     The alpha and beta chains of a TCR of the present invention may be encoded by nucleic acids located in separate vectors or may be encoded by polynucleotides located in the same vector. 
     Achieving high-level TCR surface expression requires that both the TCR-alpha and TCR-beta chains of the introduced TCR be transcribed at high levels. To do so, the TCR-alpha and TCR-beta chains of the present description may be cloned into bi-cistronic constructs in a single vector, which has been shown to be capable of over-coming this obstacle. The use of a viral intraribosomal entry site (IRES) between the TCR-alpha and TCR-beta chains results in the coordinated expression of both chains, because the TCR-alpha and TCR-beta chains are generated from a single transcript that is broken into two proteins during translation, ensuring that an equal molar ratio of TCR-alpha and TCR-beta chains are produced (Schmitt et al., 2009). 
     Nucleic acids encoding TCRs of the present description may be codon optimized to increase expression from a host cell. Redundancy in the genetic code allows some amino acids to be encoded by more than one codon, but certain codons are less “optimal” than others because of the relative availability of matching tRNAs as well as other factors (Gustafsson et al., 2004). Modifying the TCR-alpha and TCR-beta gene sequences such that each amino acid is encoded by the optimal codon for mammalian gene expression, as well as eliminating mRNA instability motifs or cryptic splice sites, has been shown to significantly enhance TCR-alpha and TCR-beta gene expression (Scholten et al., 2006). 
     Furthermore, mispairing between the introduced and endogenous TCR chains may result in the acquisition of specificities that pose a significant risk for autoimmunity. For example, the formation of mixed TCR dimers may reduce the number of CD3 molecules available to form properly paired TCR complexes, and therefore can significantly decrease the functional avidity of the cells expressing the introduced TCR (Kuball et al., 2007). 
     To reduce mispairing, the C-terminus domain of the introduced TCR chains of the present description may be modified in order to promote interchain affinity, while de-creasing the ability of the introduced chains to pair with the endogenous TCR. These strategies may include replacing the human TCR-alpha and TCR-beta C-terminus domains with their murine counterparts (murinized C-terminus domain); generating a second interchain disulfide bond in the C-terminus domain by introducing a second cysteine residue into both the TCR-alpha and TCR-beta chains of the introduced TCR (cysteine modification); swapping interacting residues in the TCR-alpha and TCR-beta chain C-terminus domains (“knob-in-hole”); and fusing the variable domains of the TCR-alpha and TCR-beta chains directly to CD3ζ (CD3ζ fusion) (Schmitt et al., 2009). 
     In an embodiment, a host cell is engineered to express a TCR of the present description. In preferred embodiments, the host cell is a human T-cell or T-cell progenitor. In some embodiments the T-cell or T-cell progenitor is obtained from a cancer patient. In other embodiments the T-cell or T-cell progenitor is obtained from a healthy donor. Host cells of the present description can be allogeneic or autologous with respect to a patient to be treated. In one embodiment, the host is a gamma/delta T-cell transformed to express an alpha/beta TCR. 
     A “pharmaceutical composition” is a composition suitable for administration to a human being in a medical setting. Preferably, a pharmaceutical composition is sterile and produced according to GMP guidelines. 
     The pharmaceutical compositions comprise the peptides either in the free form or in the form of a pharmaceutically acceptable salt (see also above). As used herein, “a pharmaceutically acceptable salt” refers to a derivative of the disclosed peptides wherein the peptide is modified by making acid or base salts of the agent. For example, acid salts are prepared from the free base (typically wherein the neutral form of the drug has a neutral —NH 2  group) involving reaction with a suitable acid. Suitable acids for preparing acid salts include both organic acids, e.g., acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methane sulfonic acid, ethane sulfonic acid, p-toluene sulfonic acid, salicylic acid, and the like, as well as inorganic acids, e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid phosphoric acid and the like. Conversely, preparation of basic salts of acid moieties which may be present on 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 as salts of acetic acid (acetates), trifluoro acetates or hydrochloric acid (chlorides). 
     Preferably, the medicament of the present invention is an immunotherapeutic such as a vaccine. It may be administered directly into the patient, into the affected organ or systemically i.d., i.m., s.c., i.p. and i.v., or applied ex vivo to cells derived from the patient or a human cell line which are subsequently administered to the patient or used in vitro to select a subpopulation of immune cells derived from the patient, which are then re-administered to the patient. If the nucleic acid is administered to cells in vitro, it may be useful for the cells to be transfected so as to co-express immune-stimulating cytokines, such as interleukin-2. The peptide may be substantially pure or combined with an immune-stimulating adjuvant (see below) or used in combination with immune-stimulatory cytokines, or be administered with a suitable delivery system, for example liposomes. The peptide may also be conjugated to a suitable carrier such as keyhole limpet haemocyanin (KLH) or mannan (see WO 95/18145 and (Longenecker et al., 1993)). The peptide may also be tagged, may be a fusion protein, or may be a hybrid molecule. The peptides whose sequence is given in the present invention are expected to stimulate CD4 or CD8 T cells. However, stimulation of CD8 T cells is more efficient in the presence of help provided by CD4 T-helper cells. Thus, for MHC Class I epitopes that stimulate CD8 T cells the fusion partner or sections of a hybrid molecule suitably provide epitopes which stimulate CD4-positive T cells. CD4- and CD8-stimulating 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 SEQ ID No. 1 to SEQ ID No. 383 and SEQ ID NO: 448 to SEQ ID NO: 499, and at least one additional peptide, preferably two to 50, more preferably two to 25, even more preferably two to 20 and most preferably two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen or eighteen peptides. The peptide(s) may be derived from one or more specific TAAs and may bind to MHC class I molecules. 
     A further aspect of the invention provides a nucleic acid (for example a polynucleotide) encoding a peptide or peptide variant of the invention. The polynucleotide may be, for example, DNA, cDNA, PNA, RNA or combinations thereof, either single- and/or double-stranded, or native or stabilized forms of polynucleotides, such as, for example, polynucleotides with a phosphorothioate backbone and it may or may not contain introns so long as it codes for the peptide. Of course, only peptides that contain naturally occurring amino acid residues joined by naturally occurring peptide bonds are encodable by a polynucleotide. A still further aspect of the invention provides an expression vector capable of expressing a polypeptide according to the invention. 
     A variety of methods have been developed to link polynucleotides, especially DNA, to vectors for example via complementary cohesive termini. For instance, complementary homopolymer tracts can be added to the DNA segment to be inserted to the vector DNA. The vector and DNA segment are then joined by hydrogen bonding between the complementary homopolymeric tails to form recombinant DNA molecules. 
     Synthetic linkers containing one or more restriction sites provide an alternative method of joining the DNA segment to vectors. Synthetic linkers containing a variety of restriction endonuclease sites are commercially available from a number of sources including International Biotechnologies Inc. New Haven, Conn., USA. 
     A desirable method of modifying the DNA encoding the polypeptide of the invention employs the polymerase chain reaction as disclosed by Saiki R K, et al. (Saiki et al., 1988). This method may be used for introducing the DNA into a suitable vector, for example by engineering in suitable restriction sites, or it may be used to modify the DNA in other useful ways as is known in the art. If viral vectors are used, pox- or adenovirus vectors are preferred. 
     The DNA (or in the case of retroviral vectors, RNA) may then 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 may be used in accordance with known techniques, appropriately modified in view of the teachings contained herein, to construct an expression vector, which is then used to transform an appropriate host cell for the expression and production of the polypeptide of the invention. Such techniques include those disclosed, for example, in U.S. Pat. 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 4,810,648. 
     The DNA (or in the case of retroviral vectors, RNA) encoding the polypeptide constituting the compound of the invention may be joined to a wide variety of other DNA sequences for introduction into an appropriate host. The companion DNA will depend upon the nature of the host, the manner of the introduction of the DNA into the host, and whether episomal maintenance or integration is desired. 
     Generally, the DNA is inserted into an expression vector, such as a plasmid, in proper orientation and correct reading frame for expression. If necessary, the DNA may be linked to the appropriate transcriptional and translational regulatory control nucleotide sequences recognized by the desired host, although such controls are generally available in the expression vector. The vector is then introduced into the host through standard techniques. Generally, not all of the hosts will be transformed by the vector. Therefore, it will be necessary to select for transformed host cells. One selection technique involves incorporating into the expression vector a DNA sequence, with any necessary control elements, that codes for a selectable trait in the transformed cell, such as antibiotic resistance. 
     Alternatively, the gene for such selectable trait can be on another vector, which is used to co-transform the desired host cell. 
     Host cells that have been transformed by the recombinant DNA of the invention are then cultured for a sufficient time and under appropriate conditions known to those skilled in the art in view of the teachings disclosed herein to permit the expression of the polypeptide, which can then be recovered. 
     Many expression systems are known, including bacteria (for example  E. coli  and  Bacillus subtilis ), yeasts (for example  Saccharomyces cerevisiae ), filamentous fungi (for example  Aspergillus  spec.), plant cells, animal cells and insect cells. Preferably, the system can be mammalian cells such as CHO cells available from the ATCC Cell Biology Collection. 
     A typical mammalian cell vector plasmid for constitutive expression comprises the CMV or SV40 promoter with a suitable poly A tail and a resistance marker, such as neomycin. One example is pSVL available from Pharmacia, Piscataway, N.J., USA. An example of an inducible mammalian expression vector is pMSG, also available from Pharmacia. Useful yeast plasmid vectors are pRS403-406 and pRS413-416 and are generally available from Stratagene Cloning Systems, La Jolla, Calif. 92037, USA. Plasmids pRS403, pRS404, pRS405 and pRS406 are Yeast Integrating plasmids (YIps) and incorporate the yeast selectable markers HIS3, TRP1, LEU2 and URA3. Plasmids pRS413-416 are Yeast Centromere plasmids (Ycps). CMV promoter-based vectors (for example from Sigma-Aldrich) provide transient or stable expression, cytoplasmic expression or secretion, and N-terminal or C-terminal tagging in various combinations of FLAG, 3×FLAG, c-myc or MAT. These fusion proteins allow for detection, purification and analysis of recombinant protein. Dual-tagged fusions provide flexibility in detection. 
     The strong human cytomegalovirus (CMV) promoter regulatory region drives constitutive protein expression levels as high as 1 mg/L in COS cells. For less potent cell lines, protein levels are typically ˜0.1 mg/L. The presence of the SV40 replication origin will result in high levels of DNA replication in SV40 replication permissive COS cells. CMV vectors, for example, can contain the pMB1 (derivative of pBR322) origin for replication in bacterial cells, the b-lactamase gene for ampicillin resistance selection in bacteria, hGH polyA, and the f1 origin. Vectors containing the pre-pro-trypsin leader (PPT) sequence can direct the secretion of FLAG fusion proteins into the culture medium for purification using ANTI-FLAG antibodies, resins, and plates. Other vectors and expression systems are well known in the art for use with a variety of host cells. 
     In another embodiment two or more peptides or peptide variants of the invention are encoded and thus expressed in a successive order (similar to “beads on a string” constructs). In doing so, the peptides or peptide variants may be linked or fused together by stretches of linker amino acids, such as for example LLLLLL (SEQ ID NO: 500), or may be linked without any additional peptide(s) between them. These constructs can also be used for cancer therapy and may induce immune responses both involving MHC I and MHC II. 
     The present invention also relates to a host cell transformed with a polynucleotide vector construct of the present invention. The host cell can be either prokaryotic or eukaryotic. Bacterial cells may be preferred prokaryotic host cells in some circumstances and typically are a strain of  E. coli  such as, for example, the  E. coli  strains DH5 available from Bethesda Research Laboratories Inc., Bethesda, Md., USA, and RR1 available from the American Type Culture Collection (ATCC) of Rockville, Md., USA (No ATCC 31343). Preferred eukaryotic host cells include yeast, insect and mammalian cells, preferably vertebrate cells such as those from a mouse, rat, monkey or human fibroblastic and colon cell lines. Yeast host cells include YPH499, YPH500 and YPH501, which are generally available from Stratagene Cloning Systems, La Jolla, Calif. 92037, USA. Preferred mammalian host cells include Chinese hamster ovary (CHO) cells available from the ATCC as CCL61, NIH Swiss mouse embryo cells NIH/3T3 available from the ATCC as CRL 1658, monkey kidney-derived COS-1 cells available from the ATCC as CRL 1650 and 293 cells which are human embryonic kidney cells. Preferred insect cells are Sf9 cells which can be transfected with baculovirus expression vectors. An overview regarding the choice of suitable host cells for expression can be found in, for example, the textbook of 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 literature known to the person of skill. 
     Transformation of appropriate cell hosts with a DNA construct of the present invention is accomplished by well-known methods that typically depend on the type of vector used. With regard to transformation of prokaryotic host cells, see, for example, Cohen et al. (Cohen et al., 1972) and (Green and Sambrook, 2012). Transformation of yeast cells is described in Sherman et al. (Sherman et al., 1986). The method of Beggs (Beggs, 1978) is also useful. With regard to vertebrate cells, reagents useful in transfecting such cells, for example calcium phosphate and DEAE-dextran or liposome formulations, are available from Stratagene Cloning Systems, or Life Technologies Inc., Gaithersburg, Md. 20877, USA. Electroporation is also useful for transforming and/or transfecting cells and is well known in the art for transforming yeast cell, bacterial cells, insect cells and vertebrate cells. 
     Successfully transformed cells, i.e. cells that contain a DNA construct of the present invention, can be identified by well-known techniques such as PCR. Alternatively, the presence of the protein in the supernatant can be detected using antibodies. 
     It will be appreciated that certain host cells of the invention are useful in the preparation of the peptides of the invention, for example bacterial, yeast and insect cells. However, other host cells may be useful in certain therapeutic methods. For example, antigen-presenting cells, such as dendritic cells, may usefully be used to express the peptides of the invention such that they may be loaded into appropriate MHC molecules. Thus, the current invention provides a host cell comprising a nucleic acid or an expression vector according to the invention. 
     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 prostatic acid phosphatase (PAP) were approved by the U.S. Food and Drug Administration (FDA) on Apr. 29, 2010, to treat asymptomatic or minimally symptomatic metastatic HRPC (Sipuleucel-T) (Rini et al., 2006; Small et al., 2006). 
     A further aspect of the invention provides a method of producing a peptide or its variant, the method comprising culturing a host cell and isolating the peptide from the host cell or its culture medium. 
     In another embodiment, the peptide, the nucleic acid or the expression vector of the invention are used in medicine. For example, the peptide or its variant may be prepared for intravenous (i.v.) injection, sub-cutaneous (s.c.) injection, intradermal (i.d.) injection, intraperitoneal (i.p.) injection, intramuscular (i.m.) injection. Preferred methods of peptide injection include s.c., i.d., i.p., i.m., and i.v. Preferred methods of DNA injection include i.d., i.m., s.c., i.p. and i.v. Doses of e.g. between 50 μg and 1.5 mg, preferably 125 μg to 500 μg, of peptide or DNA may be given and will depend on the respective peptide or DNA. Dosages of this range were successfully used in previous trials (Walter et al., 2012). 
     The polynucleotide used for active vaccination may be substantially pure or contained in a suitable vector or delivery system. The nucleic acid may be DNA, cDNA, PNA, RNA or a combination thereof. Methods for designing and introducing such a nucleic acid are well known in the art. An overview is provided by e.g. Teufel et al. (Teufel et al., 2005). Polynucleotide vaccines are easy to prepare, but the mode of action of these vectors in inducing an immune response is not fully understood. Suitable vectors and delivery systems include viral DNA and/or RNA, such as systems based on adenovirus, vaccinia virus, retroviruses, herpes virus, adeno-associated virus or hybrids containing elements of more than one virus. Non-viral delivery systems include cationic lipids and cationic polymers and are well known in the art of DNA delivery. Physical delivery, such as via a “gene-gun” may also be used. The peptide or peptides encoded by the nucleic acid may be a fusion protein, for example with an epitope that stimulates T cells for the respective opposite CDR as noted above. 
     The medicament of the invention may also include one or more adjuvants. Adjuvants are substances that non-specifically enhance or potentiate the immune response (e.g., immune responses mediated by CD8-positive T cells and helper-T (TH) cells to an antigen and would thus be considered useful in the medicament of the present invention. Suitable adjuvants include, but are not limited to, 1018 ISS, aluminum salts, AMPLIVAX®, AS15, BCG, CP-870,893, CpG7909, CyaA, dSLIM, flagellin or TLR5 ligands derived from flagellin, FLT3 ligand, GM-CSF, IC30, IC31, Imiquimod (ALDARA®), resiquimod, ImuFact IMP321, Interleukins as IL-2, IL-13, IL-21, Interferon-alpha or -beta, or pegylated derivatives thereof, IS Patch, ISS, ISCOMATRIX, ISCOMs, JuvImmune®, 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-197-MP-EC, ONTAK, OspA, PepTel® vector system, poly(lactid co-glycolid) [PLG]-based and dextran microparticles, talactoferrin SRL172, Virosomes and other Virus-like particles, YF-17D, VEGF trap, R848, beta-glucan, Pam3Cys, Aquila&#39;s QS21 stimulon, which is derived from saponin, mycobacterial extracts and synthetic bacterial cell wall mimics, and other proprietary adjuvants such as Ribi&#39;s Detox, Quil, or Superfos. Adjuvants such as Freund&#39;s or GM-CSF are preferred. Several immunological adjuvants (e.g., MF59) specific for dendritic cells and their preparation have been described previously (Allison and Krummel, 1995). Also cytokines may be used. Several cytokines have been directly linked to influencing dendritic cell migration to lymphoid tissues (e.g., TNF-), accelerating the maturation of dendritic cells into efficient antigen-presenting cells for T-lymphocytes (e.g., GM-CSF, IL-1 and IL-4) (U.S. Pat. No. 5,849,589, specifically incorporated herein by reference in its entirety) and acting as immunoadjuvants (e.g., IL-12, IL-15, IL-23, IL-7, IFN-alpha. IFN-beta) (Gabrilovich et al., 1996). 
     CpG immunostimulatory oligonucleotides have also been reported to enhance the effects of adjuvants in a vaccine setting. Without being bound by theory, CpG oligonucleotides act by activating the innate (non-adaptive) immune system via Toll-like receptors (TLR), mainly TLR9. CpG triggered TLR9 activation enhances antigen-specific humoral and cellular responses to a wide variety of antigens, including peptide or protein antigens, live or killed viruses, dendritic cell vaccines, autologous cellular vaccines and polysaccharide conjugates in both prophylactic and therapeutic vaccines. More importantly it enhances dendritic cell maturation and differentiation, resulting in enhanced activation of TH1 cells and strong cytotoxic T-lymphocyte (CTL) generation, even in the absence of CD4 T cell help. The TH1 bias induced by TLR9 stimulation is maintained even in the presence of vaccine adjuvants such as alum or incomplete Freund&#39;s adjuvant (IFA) that normally promote a TH2 bias. 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 for inducing a strong response when the antigen is relatively weak. They also accelerate the immune response and enable the antigen doses to be reduced by approximately two orders of magnitude, with comparable antibody responses to the full-dose vaccine without CpG in some experiments (Krieg, 2006). U.S. Pat. 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 CpG TLR9 antagonist is dSLIM (double Stem Loop Immunomodulator) by Mologen (Berlin, Germany) which is a preferred component of the pharmaceutical composition of the present invention. Other TLR binding molecules such as RNA binding TLR 7, TLR 8 and/or TLR 9 may also be used. 
     Other examples for useful adjuvants include, but are not limited to chemically modified CpGs (e.g. CpR, Idera), dsRNA analogues such as Poly(I:C) and derivates thereof (e.g. AmpliGen®, Hiltonal®, poly-(ICLC), poly(IC-R), poly(I:C12U), non-CpG bacterial DNA or RNA as well as immunoactive small molecules and antibodies such as cyclophosphamide, sunitinib, immune checkpoint inhibitors including ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and cemiplimab, Bevacizumab®, celebrex, NCX-4016, sildenafil, tadalafil, vardenafil, sorafenib, temozolomide, temsirolimus, XL-999, CP-547632, pazopanib, VEGF Trap, ZD2171, AZD2171, anti-CTLA4, other antibodies targeting key structures of the immune system (e.g. anti-CD40, anti-TGFbeta, anti-TNFalpha receptor) and SC58175, which may act therapeutically and/or as an adjuvant. The amounts and concentrations of adjuvants and additives useful in the context of the present invention can readily be determined by the skilled artisan without undue experimentation. 
     Preferred adjuvants are anti-CD40, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, atezolizumab, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23. 
     In a preferred embodiment, 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, resiquimod, and interferon-alpha. 
     In a preferred embodiment, 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 a preferred embodiment of the pharmaceutical composition according to the invention, the adjuvant is cyclophosphamide, imiquimod or resiquimod. Even more preferred adjuvants are Montanide IMS 1312, Montanide ISA 206, Montanide ISA 50V, Montanide ISA-51, poly-ICLC (Hiltonal®) and anti-CD40 mAB, or combinations thereof. 
     This composition is used for parenteral administration, such as subcutaneous, intradermal, intramuscular or oral administration. For this, the peptides and optionally other molecules are dissolved or suspended in a pharmaceutically acceptable, preferably aqueous carrier. In addition, the composition can contain excipients, such as buffers, binding agents, blasting agents, diluents, flavors, lubricants, etc. The peptides can also be administered together with immune stimulating substances, such as cytokines. An extensive listing of excipients that can be used in such a composition, can be, for example, taken from A. Kibbe, Handbook of Pharmaceutical Excipients (Kibbe, 2000). The composition can be used for a prevention, prophylaxis and/or therapy of adenomatous or cancerous diseases. Exemplary formulations can be found in, for example, EP2112253. 
     It is important to realize that the immune response triggered by the vaccine according to the invention attacks the cancer in different cell-stages and different stages of development. Furthermore different cancer associated signaling pathways are attacked. This is an advantage over vaccines that address only one or few targets, which may cause the tumor to easily adapt to the attack (tumor escape). Furthermore, not all individual tumors express the same pattern of antigens. Therefore, a combination of several tumor-associated peptides ensures that every single tumor bears at least some of the targets. The composition is designed in such a way that each tumor is expected to express several of the antigens and cover several independent pathways necessary for tumor growth and maintenance. Thus, the vaccine can easily be used “off-the-shelf” for a larger patient population. This means that a pre-selection of patients to be treated with the vaccine can be restricted to HLA typing, does not require any additional biomarker assessments for antigen expression, but it is still ensured that several targets are simultaneously attacked by the induced immune response, which is important for efficacy (Banchereau et al., 2001; Walter et al., 2012). 
     As used herein, the term “scaffold” refers to a molecule that specifically binds to an (e.g. antigenic) determinant. In one embodiment, a scaffold is able to direct the entity to which it is attached (e.g. a (second) antigen binding moiety) to a target site, for example to a specific type of tumor cell or tumor stroma bearing the antigenic determinant (e.g. the complex of a peptide with MHC, according to the application at hand). In another embodiment a scaffold is able to activate signaling through its target antigen, for example a T cell receptor complex antigen. Scaffolds include but are not limited to antibodies and fragments thereof, antigen binding domains of an antibody, comprising an antibody heavy chain variable region and an antibody light chain variable region, binding proteins comprising at least one ankyrin repeat motif and single domain antigen binding (SDAB) molecules, aptamers, (soluble) TCRs and (modified) cells such as allogenic or autologous T cells. To assess whether a molecule is a scaffold binding to a target, binding assays can be performed. 
     “Specific” binding means that the scaffold binds the peptide-MHC-complex of interest better than other naturally occurring peptide-MHC-complexes, to an extent that a scaffold armed with an active molecule that is able to kill a cell bearing the specific target is not able to kill another cell without the specific target but presenting other peptide-MHC complex(es). Binding to other peptide-MHC complexes is irrelevant if the peptide of the cross-reactive peptide-MHC is not naturally occurring, i.e. not derived from the human HLA-peptidome. Tests to assess target cell killing are well known in the art. They should be performed using target cells (primary cells or cell lines) with unaltered peptide-MHC presentation, or cells loaded with peptides such that naturally occurring peptide-MHC levels are reached. 
     Each scaffold can comprise a labelling which provides that the bound scaffold can be detected by determining the presence or absence of a signal provided by the label. For example, the scaffold can be labelled with a fluorescent dye or any other applicable cellular marker molecule. Such marker molecules are well known in the art. For example a fluorescence-labelling, for example provided by a fluorescence dye, can provide a visualization of the bound aptamer by fluorescence or laser scanning microscopy or flow cytometry. 
     Each scaffold can be conjugated with a second active molecule such as for example IL-21, anti-CD3, and anti-CD28. 
     For further information on polypeptide scaffolds see for example the background section of WO 2014/071978A1 and the references cited therein. 
     The present invention further relates to aptamers. Aptamers (see for example WO 2014/191359 and the literature as cited therein) are short single-stranded nucleic acid molecules, which can fold into defined three-dimensional structures and recognize specific target structures. They have appeared to be suitable alternatives for developing targeted therapies. Aptamers have been shown to selectively bind to a variety of complex targets with high affinity and specificity. 
     Aptamers recognizing cell surface located molecules have been identified within the past decade and provide means for developing diagnostic and therapeutic approaches. Since aptamers have been shown to possess almost no toxicity and immunogenicity they are promising candidates for biomedical applications. Indeed aptamers, for example prostate-specific membrane-antigen recognizing aptamers, have been successfully employed for targeted therapies and shown to be functional in xenograft in vivo models. Furthermore, aptamers recognizing specific tumor cell lines have been identified. 
     DNA aptamers can be selected to reveal broad-spectrum recognition properties for various cancer cells, and particularly those derived from solid tumors, while non-tumorigenic and primary healthy cells are not recognized. If the identified aptamers recognize not only a specific tumor sub-type but rather interact with a series of tumors, this renders the aptamers applicable as so-called broad-spectrum diagnostics and therapeutics. 
     Further, investigation of cell-binding behavior with flow cytometry showed that the aptamers revealed very good apparent affinities that are within the nanomolar range. 
     Aptamers are useful for diagnostic and therapeutic purposes. Further, it could be shown that some of the aptamers are taken up by tumor cells and thus can function as molecular vehicles for the targeted delivery of anti-cancer agents such as siRNA into tumor cells. 
     Aptamers can be selected against complex targets such as cells and tissues and complexes of the peptides comprising, preferably consisting of, a sequence according to any of SEQ ID NO 1 to SEQ ID NO 383 and SEQ ID NO: 448 to SEQ ID NO: 499, according to the invention at hand with the MHC molecule, using the cell-SELEX (Systematic Evolution of Ligands by Exponential enrichment) technique. 
     The peptides of the present invention can be used to generate and develop specific antibodies against MHC/peptide complexes. These can be used for therapy, targeting toxins or radioactive substances to the diseased tissue. Another use of these antibodies can be targeting radionuclides to the diseased tissue for imaging purposes such as PET. This use can help to detect small metastases or to determine the size and precise localization of diseased tissues. 
     Therefore, it is a further aspect of the invention to provide a method for producing a recombinant antibody specifically binding to a human major histocompatibility complex (MHC) class I or II being complexed with a HLA-restricted antigen (preferably a peptide according to the present invention), the method comprising: immunizing a genetically engineered non-human mammal comprising cells expressing said human major histocompatibility complex (MHC) class I or II with a soluble form of a MHC class I or II molecule being complexed with said HLA-restricted antigen; isolating mRNA molecules from antibody producing cells of said non-human mammal; producing a phage display library displaying protein molecules encoded by said mRNA molecules; and isolating at least one phage from said phage display library, said at least one phage displaying said antibody specifically binding to said human major histocompatibility complex (MHC) class I or II being complexed with said HLA-restricted antigen. 
     It is thus a further aspect of the invention to provide an antibody that specifically binds to a human major histocompatibility complex (MHC) class I or II being complexed with an HLA-restricted antigen, wherein the antibody preferably is a polyclonal antibody, monoclonal antibody, bi-specific antibody and/or a chimeric antibody. 
     Respective methods for producing such antibodies and single chain class I major histocompatibility complexes, as well as other tools for the production of these antibodies are disclosed in WO 03/068201, WO 2004/084798, WO 01/72768, WO 03/070752, and in publications (Cohen et al., 2003a; Cohen et al., 2003b; Denkberg et al., 2003), which for the purposes of the present invention are all explicitly incorporated by reference in their entireties. 
     Preferably, the antibody is binding with a binding affinity of below 20 nanomolar, preferably of below 10 nanomolar, to the complex, which is also regarded as “specific” in the context of the present invention. 
     The present invention relates to a peptide comprising a sequence that is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499, or a variant thereof which is at least 88% homologous (preferably identical) to SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499 or a variant thereof that induces T cells cross-reacting with said peptide, wherein said peptide is not the underlying full-length polypeptide. 
     The present invention further relates to a peptide comprising a sequence that is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499 or a variant thereof which is at least 88% homologous (preferably identical) to SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499, wherein said peptide or variant has an overall length of between 8 and 100, preferably between 8 and 30, and most preferred between 8 and 14 amino acids. 
     The present invention further relates to the peptides according to the invention that have the ability to bind to a molecule of the human major histocompatibility complex (MHC) class-I or -II. 
     The present invention further relates to the peptides according to the invention wherein the peptide consists or consists essentially of an amino acid sequence according to SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499. 
     The present invention further relates to the peptides according to the invention, wherein the peptide is (chemically) modified and/or includes non-peptide bonds. 
     The present invention further relates to the peptides according to the invention, wherein the peptide is part of a fusion protein, in particular comprising N-terminal amino acids of the HLA-DR antigen-associated invariant chain (Ii), or wherein the peptide is fused to (or into) an antibody, such as, for example, an antibody that is specific for dendritic cells. 
     The present invention further relates to a nucleic acid, encoding the peptides according to the invention, provided that the peptide is not the complete (full) human protein. 
     The present invention further relates to the nucleic acid according to the invention that is DNA, cDNA, PNA, RNA or combinations thereof. 
     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 in the treatment of acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer. 
     The present invention further relates to a host cell comprising a nucleic acid according to the invention or an expression vector according to the invention. 
     The present invention further relates to the host cell according to the present invention that is an antigen presenting cell, and preferably a dendritic cell. 
     The present invention further relates to a method of producing a peptide according to the present invention, said method comprising culturing the host cell according to the present invention, and isolating the peptide from said host cell or its culture medium. 
     The present invention further relates to the method according to the present invention, where-in the antigen is loaded onto class I or II MHC molecules expressed on the surface of a suitable antigen-presenting cell by contacting a sufficient amount of the 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: 383 and SEQ ID NO: 448 to SEQ ID NO: 499 or said variant amino acid sequence. 
     The present invention further relates to activated T cells, produced by the method according to the present invention, wherein said T cells selectively recognizes a cell which aberrantly expresses a polypeptide comprising an amino acid sequence according to the present invention. 
     The present invention further relates to a method of killing target cells in a patient which target cells aberrantly express a polypeptide comprising any amino acid sequence according to the present invention, the method comprising administering to the patient an effective number of T cells as according to the present invention. 
     The present invention further relates to the use of any peptide described, a nucleic acid according to the present invention, an expression vector according to the present invention, a cell according to the present invention, or an activated cytotoxic T lymphocyte according to the present invention as a medicament or in the manufacture of a medicament. The present invention further relates to a use according to the present invention, wherein the medicament is active against cancer. 
     The present invention further relates to a use according to the invention, wherein the medicament is a vaccine. The present invention further relates to a use according to the invention, wherein the medicament is active against cancer. 
     The present invention further relates to a use according to the invention, wherein said cancer cells are acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer cells or other solid or hematological tumor cells such as acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer. 
     The present invention further relates to particular marker proteins and biomarkers based on the peptides according to the present invention, herein called “targets” that can be used in the diagnosis and/or prognosis of acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer. The present invention also relates to the use of these novel targets for cancer treatment. 
     The term “antibody” or “antibodies” is used herein in a broad sense and includes both polyclonal and monoclonal antibodies. In addition to intact or “full” immunoglobulin molecules, also included in the term “antibodies” are fragments (e.g. CDRs, Fv, Fab and Fc fragments) or polymers of those immunoglobulin molecules and humanized versions of immunoglobulin molecules, as long as they exhibit any of the desired properties (e.g., specific binding of an acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer marker (poly)peptide, delivery of a toxin to an acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer cell expressing a cancer marker gene at an increased level, and/or inhibiting the activity of an acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer marker polypeptide) according to the invention. 
     Whenever possible, the antibodies of the invention may be purchased from commercial sources. The antibodies of the invention may also be generated using well-known methods. The skilled artisan will understand that either full length acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer marker polypeptides or fragments thereof may be used to generate the antibodies of the invention. A polypeptide to be used for generating an antibody of the invention may be partially or fully purified from a natural source or may be produced using recombinant DNA techniques. 
     For example, a cDNA encoding a peptide according to the present invention, such as a peptide according to SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499 polypeptide, or a variant or fragment thereof, can be expressed in prokaryotic cells (e.g., bacteria) or eukaryotic cells (e.g., yeast, insect, or mammalian cells), after which the recombinant protein can be purified and used to generate a monoclonal or polyclonal antibody preparation that specifically bind the acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer marker polypeptide used to generate the antibody according to the invention. 
     One of skill in the art will realize that the generation of two or more different sets of monoclonal or polyclonal antibodies maximizes the likelihood of obtaining an antibody with the specificity and affinity required for its intended use (e.g., ELISA, immunohistochemistry, in vivo imaging, immunotoxin therapy). The antibodies are tested for their desired activity by known methods, in accordance with the purpose for which the antibodies are to be used (e.g., ELISA, immunohistochemistry, immunotherapy, etc.; for further guidance on the generation and testing of antibodies, see, e.g., Greenfield, 2014 (Greenfield, 2014)). For example, the antibodies may be tested in ELISA assays or, Western blots, immunohistochemical staining of formalin-fixed cancers or frozen tissue sections. After their initial in vitro characterization, antibodies intended for therapeutic or in vivo diagnostic use are tested according to known clinical testing methods. 
     The term “monoclonal antibody” as used herein refers to an antibody obtained from a substantially homogeneous population of antibodies, i.e.; the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. The monoclonal antibodies herein specifically include “chimeric” antibodies in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired antagonistic activity (U.S. Pat. No. 4,816,567, which is hereby incorporated in its entirety). 
     Monoclonal antibodies of the invention may be prepared using hybridoma methods. In a hybridoma method, a mouse or other appropriate host animal is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes may be immunized in vitro. 
     The monoclonal antibodies may also be made by recombinant DNA methods, such as those described in U.S. Pat. No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). 
     In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce fragments thereof, particularly Fab fragments, can be accomplished using routine techniques known in the art. For instance, digestion can be performed using papain. Examples of papain digestion are described in WO 94/29348 and U.S. Pat. No. 4,342,566. Papain digestion of antibodies typically produces two identical antigen binding fragments, called Fab fragments, each with a single antigen binding site, and a residual Fc fragment. Pepsin treatment yields a F(ab′)2 fragment and a pFc′ fragment. 
     The antibody fragments, whether attached to other sequences or not, can also include insertions, deletions, substitutions, or other selected modifications of particular regions or specific amino acids residues, provided the activity of the fragment is not significantly altered or impaired compared to the non-modified antibody or antibody fragment. These modifications can provide for some additional property, such as to remove/add amino acids capable of disulfide bonding, to increase its bio-longevity, to alter its secretory characteristics, etc. In any case, the antibody fragment must possess a bioactive property, such as binding activity, regulation of binding at the binding domain, etc. Functional or active regions of the antibody may be identified by mutagenesis of a specific region of the protein, followed by expression and testing of the expressed polypeptide. Such methods are readily apparent to a skilled practitioner in the art and can include site-specific mutagenesis of the nucleic acid encoding the antibody fragment. 
     The antibodies of the invention may further comprise humanized antibodies or human antibodies. Humanized forms of non-human (e.g., murine) antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab′ or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. 
     Methods for humanizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as “import” residues, which are typically taken from an “import” variable domain. Humanization can be essentially performed by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such “humanized” antibodies are chimeric antibodies (U.S. Pat. No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted 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 are substituted by residues from analogous sites in rodent antibodies. 
     Transgenic animals (e.g., mice) that are capable, upon immunization, of producing a full repertoire of human antibodies in the absence of endogenous immunoglobulin production can be employed. For example, it has been described that the homozygous deletion of the antibody heavy chain joining region gene in chimeric and germ-line mutant mice results in complete inhibition of endogenous antibody production. Transfer of the human germ-line immunoglobulin gene array in such germ-line mutant mice will result in the production of human antibodies upon antigen challenge. Human antibodies can also be produced in phage display libraries. 
     Antibodies of the invention are preferably administered to a subject in a pharmaceutically acceptable carrier. Typically, an appropriate amount of a pharmaceutically-acceptable salt is used in the formulation to render the formulation isotonic. Examples of the pharmaceutically-acceptable carrier include saline, Ringer&#39;s solution and dextrose solution. The pH of the solution is preferably from about 5 to about 8, and more preferably from about 7 to about 7.5. Further carriers include sustained release preparations such as semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, liposomes or microparticles. It will be apparent to those persons skilled in the art that certain carriers may be more preferable depending upon, for instance, the route of administration and concentration of antibody being administered. 
     The antibodies can be administered to the subject, patient, or cell by injection (e.g., intravenous, intraperitoneal, subcutaneous, intramuscular), or by other methods such as infusion that ensure its delivery to the bloodstream in an effective form. The antibodies may also be administered by intratumoral or peritumoral routes, to exert local as well as systemic therapeutic effects. Local or intravenous injection is preferred. 
     Effective dosages and schedules for administering the antibodies may be determined empirically, and making such determinations is within the skill in the art. Those skilled in the art will understand that the dosage of antibodies that must be administered will vary depending on, for example, the subject that will receive the antibody, the route of administration, the particular type of antibody used, and other drugs being administered. A typical daily dosage of the antibody used alone might range from about 1 μg/kg to up to 100 mg/kg of body weight or more per day, depending on the factors mentioned above. Following administration of an antibody, preferably for treating acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer, the efficacy of the therapeutic antibody can be assessed in various ways well known to the skilled practitioner. For instance, the size, number, and/or distribution of cancer in a subject receiving treatment may be monitored using standard tumor imaging techniques. A therapeutically-administered antibody that arrests tumor growth, results in tumor shrinkage, and/or prevents the development of new tumors, compared to the disease course that would occurs in the absence of antibody administration, is an efficacious antibody for treatment of cancer. 
     It is a further aspect of the invention to provide a method for producing a soluble T-cell receptor (sTCR) recognizing a specific peptide-MHC complex. Such soluble T-cell receptors can be generated from specific T-cell clones, and their affinity can be increased by mutagenesis targeting the complementarity-determining regions. For the purpose of T-cell receptor selection, phage display can be used (US 2010/0113300, (Liddy et al., 2012)). For the purpose of stabilization of T-cell receptors during phage display and in case of practical use as drug, alpha and beta chain can be linked e.g. by non-native disulfide bonds, other covalent bonds (single-chain T-cell receptor), or by dimerization domains (Boulter et al., 2003; Card et al., 2004; Willcox et al., 1999). The T-cell receptor can be linked to toxins, drugs, cytokines (see, for example, US 2013/0115191), and domains recruiting effector cells such as an anti-CD3 domain, etc., in order to execute particular functions on target cells. Moreover, it could be expressed in T cells used for adoptive transfer. Further information can be found in WO 2004/033685A1 and WO 2004/074322A1. A combination of sTCRs is described in WO 2012/056407A1. Further methods for the production are disclosed in WO 2013/057586A1. 
     In addition, the peptides and/or the TCRs or antibodies or other binding molecules of the present invention can be used to verify a pathologist&#39;s diagnosis of a cancer based on a biopsied sample. 
     The antibodies or TCRs may also be used for in vivo diagnostic assays. Generally, the antibody is labeled with a radionucleotide (such as  111 In,  99 Tc,  14 C,  131 I,  3 H,  32 P or  35 S) so that the tumor can be localized using immunoscintiography. 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 above-mentioned proteins, and the affinity value (Kd) is less than 1×10 μM. 
     Antibodies for diagnostic use may be labeled with probes suitable for detection by various imaging methods. Methods for detection of probes include, but are not limited to, fluorescence, light, confocal and electron microscopy; magnetic resonance imaging 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. Additionally, probes may be bi- or multi-functional and be detectable by more than one of the methods listed. These antibodies may be directly or indirectly labeled with said probes. Attachment of probes to the antibodies includes covalent attachment of the probe, incorporation of the probe into the antibody, and the covalent attachment of a chelating compound for binding of probe, amongst others well recognized in the art. For immunohistochemistry, the disease tissue sample may be fresh or frozen or may be embedded in paraffin and fixed with a preservative such as formalin. The fixed or embedded section contains the sample are contacted with a labeled primary antibody and secondary antibody, wherein the antibody is used to detect the expression of the proteins in situ. 
     Another aspect of the present invention includes an in vitro method for producing activated T cells, the method comprising contacting in vitro T cells with antigen loaded human MHC molecules expressed on the surface of a suitable antigen-presenting cell for a period of time sufficient to activate the T cell in an antigen specific manner, wherein the antigen is 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 or has a reduced level or function of the TAP peptide transporter. Suitable cells that lack the TAP peptide transporter include T2, RMA-S and  Drosophila  cells. TAP is the transporter associated with antigen processing. 
     The human peptide loading deficient cell line T2 is available from the American Type Culture Collection, 12301 Parklawn Drive, Rockville, Md. 20852, USA under Catalogue No CRL 1992; the  Drosophila  cell line Schneider line 2 is available from the ATCC under Catalogue No CRL 19863; the mouse RMA-S cell line is described in Ljunggren et al. (Ljunggren and Karre, 1985). 
     Preferably, before transfection the host cell expresses substantially no MHC class I molecules. It is also preferred that the stimulator cell expresses a molecule important for providing a co-stimulatory signal for T-cells such as any of B7.1, B7.2, ICAM-1 and LFA 3. The nucleic acid sequences of numerous MHC class I molecules and of the co-stimulator molecules are publicly available from the GenBank and EMBL databases. 
     In case of an MHC class I epitope being used as an antigen; the T cells are CD8-positive T cells. 
     If an antigen-presenting cell is transfected to express such an epitope, preferably the cell comprises an expression vector capable of expressing a peptide containing SEQ ID NO: 1 to SEQ ID NO: 383 and SEQ ID NO: 448 to SEQ ID NO: 499, or a variant amino acid sequence thereof. 
     A number of other methods may be used for generating T cells in vitro. For example, autologous tumor-infiltrating lymphocytes can be used in the generation of CTL. Plebanski et al. (Plebanski et al., 1995) made use of autologous peripheral blood lymphocytes (PLBs) in the preparation of T cells. Furthermore, the production of autologous T cells by pulsing dendritic cells with peptide or polypeptide, or via infection with recombinant virus is possible. Also, B cells can be used in the production of autologous T cells. In addition, macrophages pulsed with peptide or polypeptide, or infected with recombinant virus, may be used in the preparation of autologous T cells. S. Walter et al. (Walter et al., 2003) describe the in vitro priming of T cells by using artificial antigen presenting cells (aAPCs), which is also a suitable way for generating T cells against the peptide of choice. In the present invention, aAPCs were generated by the coupling of preformed MHC:peptide complexes to the surface of polystyrene particles (microbeads) by biotin:streptavidin biochemistry. This system permits the exact control of the MHC density on aAPCs, which allows to selectively elicit high- or low-avidity antigen-specific T cell responses with high efficiency from blood samples. Apart from MHC:peptide complexes, aAPCs should carry other proteins with co-stimulatory activity like anti-CD28 antibodies coupled to their surface. Furthermore such aAPC-based systems often require the addition of appropriate soluble factors, e. g. cytokines, like interleukin-12. 
     Allogeneic cells may also be used in the preparation of T cells and a method is described in detail in WO 97/26328, incorporated herein by reference. For example, in addition to  Drosophila  cells and T2 cells, other cells may be used to present antigens such as CHO cells, baculovirus-infected insect cells, bacteria, yeast, and vaccinia-infected target cells. In addition plant viruses may be used (see, for example, Porta et al. (Porta et al., 1994) which describes the development of cowpea mosaic virus as a high-yielding system for the presentation of foreign peptides. 
     The activated T cells that are directed against the peptides of the invention are useful in therapy. Thus, a further aspect of the invention provides activated T cells obtainable by the foregoing methods of the invention. 
     Activated T cells, which are produced by the above method, will selectively recognize a cell that aberrantly expresses a polypeptide that comprises an amino acid sequence of SEQ ID NO: 1 to SEQ ID NO 383 and SEQ ID NO: 448 to SEQ ID NO: 499. 
     Preferably, the T cell recognizes the cell by interacting through its TCR with the HLA/peptide-complex (for example, binding). The T cells are useful in a method of killing target cells in a patient whose target cells aberrantly express a polypeptide comprising an amino acid sequence of the invention wherein the patient is administered an effective number of the activated T cells. The T cells that are administered to the patient may be derived from the patient and activated as described above (i.e. they are autologous T cells). Alternatively, the T cells are not from the patient but are from another individual. Of course, it is preferred if the individual is a healthy individual. By “healthy individual” the inventors mean that the individual is generally in good health, preferably has a competent immune system and, more preferably, is not suffering from any disease that can be readily tested for and detected. 
     In vivo, the target cells for the CD8-positive T cells according to the present invention can be cells of the tumor (which sometimes express MHC class II) and/or stromal cells surrounding the tumor (tumor cells) (which sometimes also express MHC class II; (Dengjel et al., 2006)). 
     The T cells of the present invention may be used as active ingredients of a therapeutic composition. Thus, the invention also provides a method of killing target cells in a patient whose target cells aberrantly express a polypeptide comprising an amino acid sequence of the invention, the method comprising administering to the patient an effective number of T cells as defined above. 
     By “aberrantly expressed” the inventors also mean that the polypeptide is over-expressed compared to levels of expression in normal tissues or that the gene is silent in the tissue from which the tumor is derived but, in the tumor, it is expressed. By “over-expressed” the inventors mean that the polypeptide is present at a level at least 2-fold of that present in normal tissue; preferably at least 3-fold, and more preferably at least 5-fold or 10-fold the level present in normal tissue. 
     T cells may be obtained by methods known in the art, e.g. those described above. 
     Protocols for this so-called adoptive transfer of T cells are well known in the art. Reviews can be found in: Gattioni et al. and 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 is introduced into a host cell, preferably a T cell. This engineered T cell can then be transferred to a patient for therapy of cancer. 
     Any molecule of the invention, i.e. the peptide, nucleic acid, antibody, expression vector, cell, activated T cell, T-cell receptor or the nucleic acid encoding it, is useful for the treatment of disorders, characterized by cells escaping an immune response. Therefore any molecule of the present invention may be used as medicament or in the manufacture of a medicament. The molecule may be used by itself or combined with other molecule(s) of the invention or (a) known molecule(s). 
     The present invention is further directed at a kit comprising: 
     (a) a container containing a pharmaceutical composition as described above, in solution or in lyophilized form; 
     (b) optionally a second container containing a diluent or reconstituting solution for the lyophilized formulation; and 
     (c) optionally, instructions for (i) use of the solution or (ii) reconstitution and/or use of the lyophilized formulation. 
     The kit may further comprise one or more of (iii) a buffer, (iv) a diluent, (v) a filter, (vi) a needle, or (v) a syringe. The container is preferably a bottle, a vial, a syringe or test tube; and it may be a multi-use container. The pharmaceutical composition is preferably lyophilized. 
     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 (e.g. dual chamber vials), syringes (such as dual chamber syringes) and test tubes. The container may be formed from a variety of materials such as glass or plastic. Preferably the kit and/or container contain/s instructions on or associated with the container that indicates directions for reconstitution and/or use. For example, the label may indicate that the lyophilized formulation is to be reconstituted to peptide concentrations as described above. The label may further indicate that the formulation is useful or intended for subcutaneous administration. 
     The container holding the formulation may be a multi-use vial, which allows for repeat administrations (e.g., from 2-6 administrations) of the reconstituted formulation. The kit may further comprise a second container comprising a suitable diluent (e.g., sodium bicarbonate solution). 
     Upon mixing of the diluent and the lyophilized formulation, the final peptide concentration in the reconstituted formulation is preferably at least 0.15 mg/mL/peptide (=75 μg) and preferably not more than 3 mg/mL/peptide (=1500 μg). The kit may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, syringes, and package inserts with instructions for use. 
     Kits of the present invention may have a single container that contains the formulation of the pharmaceutical compositions according to the present invention with or without other components (e.g., other compounds or pharmaceutical compositions of these other compounds) or may have distinct container for each component. 
     Preferably, kits of the invention include a formulation of the invention packaged for use in combination with the co-administration of a second compound (such as adjuvants (e.g. GM-CSF), a chemotherapeutic agent, a natural product, a hormone or antagonist, an anti-angiogenesis agent or inhibitor, an apoptosis-inducing agent or a chelator) or a pharmaceutical composition thereof. The components of the kit may be pre-complexed, or each component may be in a separate distinct container prior to administration to a patient. The components of the kit may be provided in one or more liquid solutions, preferably, an aqueous solution, more preferably, a sterile aqueous solution. The components of the kit may also be provided as solids, which may be converted into liquids by addition of suitable solvents, which are preferably provided in another distinct container. 
     The container of a therapeutic kit may be a vial, test tube, flask, bottle, syringe, or any other means of enclosing a solid or liquid. Usually, when there is more than one component, the kit will contain a second vial or other container, which allows for separate dosing. The kit may also contain another container for a pharmaceutically acceptable liquid. Preferably, a therapeutic kit will contain an apparatus (e.g., one or more needles, syringes, eye droppers, pipette, etc.), which enables administration of the agents of the invention that are components of the present kit. 
     The present formulation is one that is suitable for administration of the peptides by any acceptable route such as oral (enteral), nasal, ophthal, subcutaneous, intradermal, intramuscular, intravenous or transdermal. Preferably, the administration is s.c., and most preferably i.d. administration may be by infusion pump. 
     Since the peptides of the invention were isolated from acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer, the medicament of the invention is preferably used to treat acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer. 
     The present invention further relates to a method for producing a personalized pharmaceutical for an individual patient comprising manufacturing a pharmaceutical composition comprising at least one peptide selected from a warehouse of pre-screened TUMAPs, wherein the at least one peptide used in the pharmaceutical composition is selected for suitability in the individual patient. In one embodiment, the pharmaceutical composition is a vaccine. The method could also be adapted to produce T cell clones for down-stream applications, such as TCR isolations, or soluble antibodies, and other treatment options. 
     A “personalized pharmaceutical” shall mean specifically tailored therapies for one individual patient that will only be used for therapy in such individual patient, including actively personalized cancer vaccines and adoptive cellular therapies using autologous patient tissue. 
     As used herein, the term “warehouse” shall refer to a group or set of peptides that have been pre-screened for immunogenicity and/or over-presentation in a particular tumor type. The term “warehouse” is not intended to imply that the particular peptides included in the vaccine have been pre-manufactured and stored in a physical facility, although that possibility is contemplated. It is expressly contemplated that the peptides may be manufactured de novo for each individualized vaccine produced or may be pre-manufactured and stored. The warehouse (e.g. in the form of a database) is composed of tumor-associated peptides which were highly overexpressed in the tumor tissue of acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer patients with various HLA-A HLA-B and HLA-C alleles. It may contain MHC class I and MHC class II peptides or elongated MHC class I peptides. In addition to the tumor associated peptides collected from several acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer tissues, the warehouse may contain HLA-A*02, HLA-A*01, HLA-A*03, HLA-A*24, HLA-B*07, HLA-B*08 and HLA-B*44 marker peptides. These peptides allow comparison of the magnitude of T-cell immunity induced by TUMAPS in a quantitative manner and hence allow important conclusion to be drawn on the capacity of the vaccine to elicit anti-tumor responses. Secondly, they function as important positive control peptides derived from a “non-self” antigen in the case that any vaccine-induced T-cell responses to TUMAPs derived from “self” antigens in a patient are not observed. And thirdly, it may allow conclusions to be drawn, regarding the status of immunocompetence of the patient. 
     TUMAPs for the warehouse are identified by using an integrated functional genomics approach combining gene expression analysis, mass spectrometry, and T-cell immunology (XPresident®). The approach assures that only TUMAPs truly present on a high percentage of tumors but not or only minimally expressed on normal tissue, are chosen for further analysis. For initial peptide selection, acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer samples from patients and blood from healthy donors were analyzed in a stepwise approach: 
     1. HLA ligands from the malignant material were identified by mass spectrometry 
     2. Genome-wide messenger ribonucleic acid (mRNA) expression analysis was used to identify genes over-expressed in the malignant tissue (acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer) compared with a range of normal organs and tissues 
     3. Identified HLA ligands were compared to gene expression data. Peptides over-presented or selectively presented on tumor tissue, preferably encoded by selectively expressed or over-expressed genes as detected in step 2 were considered suitable TUMAP candidates for a multi-peptide vaccine. 
     4. Literature research was performed in order to identify additional evidence supporting the relevance of the identified peptides as TUMAPs 
     5. The relevance of over-expression at the mRNA level was confirmed by redetection of selected TUMAPs from step 3 on tumor tissue and lack of (or infrequent) detection on healthy tissues. 
     6. In order to assess, whether an induction of in vivo T-cell responses by the selected peptides may be feasible, in vitro immunogenicity assays were performed using human T cells from healthy donors as well as from acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer patients. 
     In an aspect, the peptides are pre-screened for immunogenicity before being included in the warehouse. By way of example, and not limitation, the immunogenicity of the peptides included in the warehouse is determined by a method comprising in vitro T-cell priming through repeated stimulations of CD8+ T cells from healthy donors with artificial antigen presenting cells loaded with peptide/MHC complexes and anti-CD28 antibody. 
     This method is preferred for rare cancers and patients with a rare expression profile. In contrast to multi-peptide cocktails with a fixed composition as currently developed, the warehouse allows a significantly higher matching of the actual expression of antigens in the tumor with the vaccine. Selected single or combinations of several “off-the-shelf” peptides will be used for each patient in a multitarget approach. In theory an approach based on selection of e.g. 5 different antigenic peptides from a library of 50 would already lead to approximately 17 million possible drug product (DP) compositions. 
     In an aspect, the peptides are selected for inclusion in the vaccine based on their suitability for the individual patient based on the method according to the present invention as described herein, or as below. 
     The HLA phenotype, transcriptomic and peptidomic data is gathered from the patient&#39;s tumor material, and blood samples to identify the most suitable peptides for each patient containing “warehouse” and patient-unique (i.e. mutated) TUMAPs. Those peptides will be chosen, which are selectively or over-expressed in the patients&#39; tumor and, where possible, show strong in vitro immunogenicity if tested with the patients&#39; individual PBMCs. 
     Preferably, the peptides included in the vaccine are identified by a method comprising: (a) identifying tumor-associated peptides (TUMAPs) presented by a tumor sample from the individual patient; (b) comparing the peptides identified in (a) with a warehouse (database) of peptides as described above; and (c) selecting at least one peptide from the warehouse (database) that correlates with a tumor-associated peptide identified in the patient. For example, the TUMAPs presented by the tumor sample are identified by: (a1) comparing expression data from the tumor sample to expression data from a sample of normal tissue corresponding to the tissue type of the tumor sample to identify proteins that are over-expressed or aberrantly expressed in the tumor sample; and (a2) correlating 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 over-expressed or aberrantly expressed by the tumor. Preferably, the sequences of MHC ligands are identified by eluting bound peptides from 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, selecting peptides using a warehousing (database) model, TUMAPs may be identified in the patient de novo, and then included in the vaccine. As one example, candidate TUMAPs may be identified in the patient by (a1) comparing expression data from the tumor sample to expression data from a sample of normal tissue corresponding to the tissue type of the tumor sample to identify proteins that are over-expressed or aberrantly expressed in the tumor sample; and (a2) correlating 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 over-expressed or aberrantly expressed by the tumor. As another example, proteins may be identified containing mutations that are unique to the tumor sample relative to normal corresponding tissue from the individual patient, and TUMAPs can be identified that specifically target the mutation. For example, the genome of the tumor and of corresponding normal tissue can be sequenced by whole genome sequencing: For discovery of non-synonymous mutations in the protein-coding regions of genes, genomic DNA and RNA are extracted from tumor tissues and normal non-mutated genomic germline DNA is extracted from peripheral blood mononuclear cells (PBMCs). The applied NGS approach is confined to the re-sequencing of protein coding regions (exome re-sequencing). For this purpose, exonic DNA from human samples is captured using vendor-supplied target enrichment kits, followed by sequencing with e.g. a HiSeq2000 (Illumina). Additionally, tumor mRNA is sequenced for direct quantification of gene expression and validation that mutated genes are expressed in the patients&#39; tumors. The resultant millions of sequence reads are processed through software algorithms. The output list contains mutations and gene expression. Tumor-specific somatic mutations are determined by comparison with the PBMC-derived germline variations and prioritized. The de novo identified peptides can then be tested for immunogenicity as described above for the warehouse, and candidate TUMAPs possessing suitable immunogenicity are selected for inclusion in the vaccine. 
     In one exemplary embodiment, the peptides included in the vaccine are identified by: (a) identifying tumor-associated peptides (TUMAPs) presented by a tumor sample from the individual patient by the method as described above; (b) comparing the peptides identified in a) with a warehouse of peptides that have been prescreened for immunogenicity and overpresentation in tumors as compared to corresponding normal tissue; (c) selecting at least one peptide from the warehouse that correlates with a tumor-associated peptide identified in the patient; and (d) optionally, selecting at least one peptide identified de novo in (a) confirming its immunogenicity. 
     In one exemplary embodiment, the peptides included in the vaccine are identified by: (a) identifying tumor-associated peptides (TUMAPs) presented by a tumor sample from the individual patient; and (b) selecting at least one peptide identified de novo in (a) and confirming its immunogenicity. 
     Once the peptides for a personalized peptide-based vaccine are selected, the vaccine is produced. The vaccine preferably is a liquid formulation consisting of the individual peptides dissolved in between 20-40% DMSO, preferably about 30-35% DMSO, such as about 33% DMSO. 
     Each peptide to be included into a product is dissolved in DMSO. The concentration of the single peptide solutions has to be chosen depending on the number of peptides to be included into the product. The single peptide-DMSO solutions are mixed in equal parts to achieve a solution containing all peptides to be included in the product with a concentration of ˜2.5 mg/ml per peptide. The mixed solution is then diluted 1:3 with water for injection to achieve a concentration of 0.826 mg/ml per peptide in 33% DMSO. The diluted solution is filtered through a 0.22 μm sterile filter. The final bulk solution is obtained. 
     Final bulk solution is filled into vials and stored at −20° C. until use. One vial contains 700 μL solution, containing 0.578 mg of each peptide. Of this, 500 μL (approx. 400 μg per peptide) will be applied for intradermal injection. 
     In addition to being useful for treating cancer, the peptides of the present invention are also useful as diagnostics. Since the peptides were generated from acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer cells and since it was determined that these peptides are not or at lower levels present in normal tissues, these peptides can be used to diagnose the presence of a cancer. 
     The presence of claimed peptides on tissue biopsies in blood samples can assist a pathologist in diagnosis of cancer. Detection of certain peptides by means of antibodies, mass spectrometry or other methods known in the art can tell the pathologist that the tissue sample is malignant or inflamed or generally diseased, or can be used as a biomarker for acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer. Presence of groups of peptides can enable classification or sub-classification of diseased tissues. 
     The detection of peptides on diseased tissue specimen can enable the decision about the benefit of therapies involving the immune system, especially if T-lymphocytes are known or expected to be involved in the mechanism of action. Loss of MHC expression is a well described mechanism by which infected of malignant cells escape immuno-surveillance. Thus, presence of peptides shows that this mechanism is not exploited by the analyzed cells. 
     The peptides of the present invention might be used to analyze lymphocyte responses against those peptides such as T cell responses or antibody responses against the peptide or the peptide complexed to MHC molecules. These lymphocyte responses can be used as prognostic markers for decision on further therapy steps. These responses can also be used as surrogate response markers in immunotherapy approaches aiming to induce lymphocyte responses by different means, e.g. vaccination of protein, nucleic acids, autologous materials, adoptive transfer of lymphocytes. In gene therapy settings, lymphocyte responses against peptides can be considered in the assessment of side effects. Monitoring of lymphocyte responses might also be a valuable tool for follow-up examinations of transplantation therapies, e.g. for the detection of graft versus host and host versus graft diseases. 
     The present invention will now be described in the following examples which describe preferred embodiments thereof, and with reference to the accompanying figures, nevertheless, without being limited thereto. For the purposes of the present invention, all references as cited herein are incorporated by reference in their entireties. 
     EXAMPLES 
     Example 1 
     Identification and Quantitation of Tumor Associated Peptides Presented on the Cell Surface 
     Tissue Samples 
     Patients&#39; tumor tissues were obtained from: Asterand (Detroit, Mich., USA &amp; Royston, Herts, UK), Bio-Options Inc. (Brea, Calif., USA), BioServe (Beltsville, Md., USA), Conversant Bio (Huntsville, Ala., USA), Geneticist Inc. (Glendale, Calif., USA), Kyoto Prefectural University of Medicine (KPUM) (Kyoto, Japan), Osaka City University (Osaka, Japan), ProteoGenex Inc. (Culver City, Calif., USA), Stanford Cancer Center (Stanford, Calif., USA), Tissue Solutions Ltd (Glasgow, UK), University Hospital Bonn (Bonn, Germany), University Hospital Geneva (Geneva, Switzerland), University Hospital Heidelberg (Heidelberg, Germany), and University Hospital Tübingen (Tübingen, Germany) 
     Normal tissues were obtained from: Asterand (Detroit, Mich., USA &amp; Royston, Herts, UK), BioServe (Beltsville, Md., USA), Capital BioScience Inc. (Rockville, Md., USA), Centre for Clinical Transfusion Medicine Tübingen (Tübingen, Germany), Geneticist Inc. (Glendale, Calif., USA), Kyoto Prefectural University of Medicine (KPUM) (Kyoto, Japan), ProteoGenex Inc. (Culver City, Calif., USA), Tissue Solutions Ltd (Glasgow, UK), and University Hospital Tübingen (Tübingen, Germany) 
     Written informed consents of all patients had been given before surgery or autopsy. Tissues were shock-frozen immediately after excision and stored until isolation of TUMAPs at −70° C. or below. 
     Isolation of HLA Peptides from Tissue Samples 
     HLA peptide pools from shock-frozen tissue samples were obtained by immune precipitation from solid tissues according to a slightly modified protocol (Falk et al., 1991; Seeger et al., 1999) using the HLA-A*02-specific antibody BB7.2, the HLA-A, —B, C-specific antibody W6/32, the HLA-DR specific antibody L243 and the HLA DP specific antibody B7/21, CNBr-activated sepharose, acid treatment, and ultrafiltration. 
     Mass Spectrometry Analyses 
     The HLA peptide pools as obtained were separated according to their hydrophobicity by reversed-phase chromatography (nanoAcquity UPLC system, Waters) and the eluting peptides were analyzed in LTQ-velos and fusion hybrid mass spectrometers (ThermoElectron) equipped with an ESI source. Peptide pools were loaded directly onto the analytical fused-silica micro-capillary column (75 μm i.d.×250 mm) packed with 1.7 μm C18 reversed-phase material (Waters) applying a flow rate of 400 nL per minute. Subsequently, the peptides were separated using a two-step 180 minute-binary gradient from 10% to 33% B at a flow rate of 300 nL per minute. The gradient was composed of Solvent A (0.1% formic acid in water) and solvent B (0.1% formic acid in acetonitrile). A gold coated glass capillary (PicoTip, New Objective) was used for introduction into the nanoESI source. The LTQ-Orbitrap mass spectrometers were operated in the data-dependent mode using a TOP5 strategy. In brief, a scan cycle was initiated with a full scan of high mass accuracy in the Orbitrap (R=30 000), which was followed by MS/MS scans also in the Orbitrap (R=7500) on the 5 most abundant precursor ions with dynamic exclusion of previously selected ions. Tandem mass spectra were interpreted by SEQUEST at a fixed false discovery rate (q≤0.05) and additional manual control. In cases where the identified peptide sequence was uncertain it was additionally validated by comparison of the generated natural peptide fragmentation pattern with the fragmentation pattern of a synthetic sequence-identical reference peptide. 
     Label-free relative LC-MS quantitation was performed by ion counting i.e. by extraction and analysis of LC-MS features (Mueller et al., 2007). The method assumes that the peptide&#39;s LC-MS signal area correlates with its abundance in the sample. Extracted features were further processed by charge state deconvolution and retention time alignment (Mueller et al., 2008; Sturm et al., 2008). Finally, all LC-MS features were cross-referenced with the sequence identification results to combine quantitative data of different samples and tissues to peptide presentation profiles. The quantitative data were normalized in a two-tier fashion according to central tendency to account for variation within technical and biological replicates. Thus each identified peptide can be associated with quantitative data allowing relative quantification between samples and tissues. In addition, all quantitative data acquired for peptide candidates was inspected manually to assure data consistency and to verify the accuracy of the automated analysis. For each peptide a presentation profile was calculated showing the mean sample presentation as well as replicate variations. The profiles juxtapose acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer samples to a baseline of normal tissue samples. Presentation profiles of exemplary over-presented peptides are shown in  FIGS.  1 A- 1 I . 
     Table 8a and 8b show the presentation on various cancer entities for selected peptides, and thus the particular relevance of the peptides as mentioned for the diagnosis and/or treatment of the cancers as indicated (e.g. peptide SEQ ID No. 22 for head and neck squamous cell carcinoma and esophageal cancer, peptide SEQ ID No. 34 for breast cancer and uterine and endometrial cancer). 
     
       
         
           
               
             
               
                 TABLE 8a 
               
             
            
               
                   
               
               
                 Overview of presentation of selected tumor-associated 
               
               
                 peptides of the present invention across entities. 
               
               
                 AML: acute myeloid leukemia; 
               
               
                 BRCA: breast cancer; 
               
               
                 CCC: cholangiocellular carcinoma; 
               
               
                 CLL: chronic lymphocytic leukemia; 
               
               
                 CRC: colorectal cancer; 
               
               
                 GBC: gallbladder cancer; 
               
               
                 GBM: glioblastoma; 
               
               
                 GC: gastric cancer; 
               
               
                 HCC: hepatocellular carcinoma; 
               
               
                 HNSCC: head and neck squamous 
               
               
                 cell carcinoma; 
               
               
                 MEL: melanoma; 
               
               
                 NHL: non-Hodgkin lymphoma; 
               
               
                 NSCLCadeno: non-small cell lung 
               
               
                 cancer adenocarcinoma; 
               
               
                 NSCLCother: NSCLC samples that could 
               
               
                 not unambiguously be assigned to 
               
               
                 NSCLCadeno or NSCLCsquam; 
               
               
                 NSCLCsquam: squamous cell non-small 
               
               
                 cell lung cancer; 
               
               
                 OC: ovarian cancer; 
               
               
                 OSCAR: esophageal cancer; 
               
               
                 PACA: pancreatic cancer; 
               
               
                 PRCA: prostate cancer; 
               
               
                 RCC: renal cell carcinoma; 
               
               
                 SCLC: small cell lung cancer; 
               
               
                 UBC: urinary bladder carcinoma; 
               
               
                 UEC: uterine and endometrial cancer. 
               
               
                 Overview of presentation of selected 
               
               
                 tumor-associated peptides of the present 
               
               
                 invention across entities. 
               
            
           
           
               
               
               
            
               
                 SEQ 
                   
                 Peptide Presentation 
               
               
                 ID No. 
                 Sequence 
                 on cancer entities 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                 RPRSLQCVSL 
                 PRCA 
               
               
                   
               
               
                 2 
                 VPGSDPARYEFL 
                 OSCAR 
               
               
                   
               
               
                 3 
                 MPYVVLTAL 
                 RCC 
               
               
                   
               
               
                 4 
                 GPKKFIVKL 
                 PRCA 
               
               
                   
               
               
                 5 
                 LPSLSHCSQL 
                 MEL 
               
               
                   
               
               
                 6 
                 LPLNSSTSL 
                 SCLC 
               
               
                   
               
               
                 8 
                 MPKTNLSKM 
                 HNSCC 
               
               
                   
               
               
                 12 
                 LPNTGRIGQLL 
                 NSCLCadeno 
               
               
                   
               
               
                 13 
                 LPNTGRIGQL 
                 PRCA 
               
               
                   
               
               
                 14 
                 AVHEIGHSL 
                 NSCLCadeno 
               
               
                   
               
               
                 15 
                 KPGFNISIL 
                 BRCA 
               
               
                   
               
               
                 16 
                 FPAPPAHWF 
                 BRCA 
               
               
                   
               
               
                 17 
                 SPAAPLSPASSL 
                 UBC 
               
               
                   
               
               
                 18 
                 MALSVLRLAL 
                 GBC, GC, NSCLCsquam, OC, OSCAR, 
               
               
                   
                   
                 PACA, PRCA, SCLC 
               
               
                   
               
               
                 20 
                 MVLGIGPVL 
                 CRC, GBC, HNSCC, NSCLCadeno, NSCLCsquam, 
               
               
                   
                   
                 OC, SCLC, UEC 
               
               
                   
               
               
                 21 
                 APSRLLEL 
                 HCC 
               
               
                   
               
               
                 22 
                 LPQLKPAL 
                 HNSCC, OSCAR 
               
               
                   
               
               
                 23 
                 VPRPTSTVGL 
                 MEL 
               
               
                   
               
               
                 24 
                 VPRPTSTVGLFL 
                 MEL 
               
               
                   
               
               
                 25 
                 RPQGAVGGL 
                 HCC 
               
               
                   
               
               
                 27 
                 RIRVTSEVL 
                 BRCA 
               
               
                   
               
               
                 29 
                 APLRVHITSL 
                 MEL 
               
               
                   
               
               
                 31 
                 RPGPSDPAA 
                 NSCLCadeno 
               
               
                   
               
               
                 32 
                 APMAPGRSPL 
                 UEC 
               
               
                   
               
               
                 33 
                 LPRGLSPARQL 
                 UEC 
               
               
                   
               
               
                 34 
                 APMAPGRSP 
                 BRCA, UEC 
               
               
                   
               
               
                 35 
                 APLPPPRAL 
                 GBM 
               
               
                   
               
               
                 36 
                 RPFSREMDL 
                 AML, OC 
               
               
                   
               
               
                 38 
                 RPSFPNLTSF 
                 AML, OC 
               
               
                   
               
               
                 39 
                 QPRPSSEKI 
                 AML 
               
               
                   
               
               
                 40 
                 FPRTVKHIDAAL 
                 CRC 
               
               
                   
               
               
                 42 
                 APLKMLAL 
                 MEL, OC 
               
               
                   
               
               
                 43 
                 APTPRPKVL 
                 BRCA 
               
               
                   
               
               
                 45 
                 TRPWSGPYIL 
                 MEL 
               
               
                   
               
               
                 46 
                 QPISGNPVTL 
                 NHL, NSCLCsquam, SCLC, UBC 
               
               
                   
               
               
                 47 
                 RPRQTGALM 
                 AML 
               
               
                   
               
               
                 48 
                 RPRYSIGL 
                 BRCA 
               
               
                   
               
               
                 49 
                 APEKARAFL 
                 OSCAR 
               
               
                   
               
               
                 50 
                 PEKARAFL 
                 OSCAR 
               
               
                   
               
               
                 51 
                 SPVFYVQTL 
                 BRCA 
               
               
                   
               
               
                 53 
                 SPRIPFSTF 
                 MEL 
               
               
                   
               
               
                 54 
                 VPSCGRSVEGL 
                 CLL, GBC, NHL, NSCLCadeno, 
               
               
                   
                   
                 OC, OSCAR, PACA, 
               
               
                   
                   
                 RCC, UEC 
               
               
                   
               
               
                 55 
                 LPALLRSGL 
                 CCC, GBC, HCC, HNSCC, NSCLCadeno, 
               
               
                   
                   
                 NSCLCsquam, OC, OSCAR, RCC, SCLC 
               
               
                   
               
               
                 56 
                 LPALLRSGLTL 
                 BRCA, CCC, CRC, GBC, HCC, 
               
               
                   
                   
                 HNSCC, MEL, NHL, 
               
               
                   
                   
                 NSCLCadeno, OC, OSCAR, RCC 
               
               
                   
               
               
                 57 
                 APLLPIRTL 
                 UBC 
               
               
                   
               
               
                 58 
                 APLLPIRTLPL 
                 UBC 
               
               
                   
               
               
                 59 
                 KPRTIYSSL 
                 OSCAR, UEC 
               
               
                   
               
               
                 60 
                 RPYSIYPHGVTF 
                 CCC, GBC, HCC 
               
               
                   
               
               
                 61 
                 LPRIPFSTF 
                 MEL 
               
               
                   
               
               
                 63 
                 FPHMATTAF 
                 HNSCC 
               
               
                   
               
               
                 64 
                 VPRPIFSQLYL 
                 NHL, UEC 
               
               
                   
               
               
                 65 
                 FPNVYSTLVL 
                 MEL 
               
               
                   
               
               
                 66 
                 LPMTVISVL 
                 GBC 
               
               
                   
               
               
                 67 
                 VPVSRPVL 
                 CLL, NHL 
               
               
                   
               
               
                 68 
                 FPNEVSVVL 
                 BRCA, MEL, NSCLCadeno, 
               
               
                   
                   
                 NSCLCsquam, OC, 
               
               
                   
                   
                 OSCAR 
               
               
                   
               
               
                 69 
                 RPEDGRPRL 
                 GBM 
               
               
                   
               
               
                 70 
                 VPAQRLGLL 
                 AML, NSCLCadeno, NSCLCsquam, 
               
               
                   
                   
                 OC, OSCAR 
               
               
                   
               
               
                 71 
                 APFAPLHGGGSL 
                 PRCA 
               
               
                   
               
               
                 72 
                 APCNGNVAV 
                 BRCA, NSCLCadeno 
               
               
                   
               
               
                 73 
                 LPVSSPVTL 
                 BRCA, NSCLCsquam 
               
               
                   
               
               
                 74 
                 VPVSHPVL 
                 CLL, NHL 
               
               
                   
               
               
                 76 
                 KPKVESQAL 
                 BRCA 
               
               
                   
               
               
                 77 
                 QPRLVPGETL 
                 GBC, MEL, NHL, NSCLCadeno, NSCLCsquam 
               
               
                   
               
               
                 78 
                 HPSQESPTL 
                 NSCLCsquam, OC, RCC, UBC, UEC 
               
               
                   
               
               
                 79 
                 GPASDHPSL 
                 OC, PRCA, UEC 
               
               
                   
               
               
                 80 
                 SALPTTISF 
                 HNSCC, OSCAR, SCLC 
               
               
                   
               
               
                 82 
                 DAAHPGPSV 
                 UEC 
               
               
                   
               
               
                 83 
                 AVSSHHNVI 
                 RCC 
               
               
                   
               
               
                 84 
                 MPMQDIKMI 
                 UEC 
               
               
                   
               
               
                 85 
                 MPMQDIKMILKM 
                 OC, SCLC 
               
               
                   
               
               
                 86 
                 ALLLRGVTL 
                 SCLC 
               
               
                   
               
               
                 87 
                 APVGGNVTSSF 
                 OSCAR 
               
               
                   
               
               
                 88 
                 KPSAVKDSIY 
                 HNSCC, RCC 
               
               
                   
               
               
                 89 
                 FLIPRAGWLAGL 
                 CRC 
               
               
                   
               
               
                 90 
                 HAIEKAFQL 
                 CRC 
               
               
                   
               
               
                 91 
                 FPRLVGPDFF 
                 OC 
               
               
                   
               
               
                 92 
                 TSPLPPTV 
                 AML, HNSCC 
               
               
                   
               
               
                 93 
                 SVAIAHGVF 
                 CLL, CRC 
               
               
                   
               
               
                 94 
                 LPMSKRQEY 
                 OC 
               
               
                   
               
               
                 95 
                 RTKEEINEL 
                 NSCLCadeno 
               
               
                   
               
               
                 96 
                 QPSLVQAIF 
                 OC 
               
               
                   
               
               
                 97 
                 LPPGTQIQI 
                 CRC 
               
               
                   
               
               
                 98 
                 FPCSALLACF 
                 OSCAR 
               
               
                   
               
               
                 99 
                 MPVSAFTVI 
                 GC, NSCLCsquam 
               
               
                   
               
               
                 100 
                 TPIPFDKILY 
                 OSCAR 
               
               
                   
               
               
                 101 
                 KPGLPGLK 
                 BRCA, CRC, GBM, HCC, 
               
               
                   
                   
                 MEL, NHL, NSCLCadeno, 
               
               
                   
                   
                 NSCLCsquam, OC, OSCAR, RCC, 
               
               
                   
                   
                 SCLC, UBC, UEC 
               
               
                   
               
               
                 102 
                 MAGPAIHTAPM 
                 HNSCC 
               
               
                   
               
               
                 105 
                 RPRYETGVCA 
                 CRC 
               
               
                   
               
               
                 106 
                 APFHIDRLF 
                 OC, RCC 
               
               
                   
               
               
                 107 
                 GQRLESPGGAA 
                 AML, CCC, CLL, CRC, 
               
               
                   
                   
                 GBC, HCC, HNSCC, 
               
               
                   
                   
                 NSCLCsquam, PACA, UBC, UEC 
               
               
                   
               
               
                 108 
                 APRGSPPI 
                 HCC, OC, OSCAR, PACA, RCC 
               
               
                   
               
               
                 110 
                 YPSSPASAV 
                 GC 
               
               
                   
               
               
                 111 
                 YPLQQTNVY 
                 RCC 
               
               
                   
               
               
                 112 
                 YPSPLNKHSF 
                 RCC 
               
               
                   
               
               
                 114 
                 FVPPSGPSNPM 
                 HNSCC 
               
               
                   
               
               
                 115 
                 KTKSLAQQL 
                 CRC, NSCLCadeno, UEC 
               
               
                   
               
               
                 116 
                 RSYQHSLRL 
                 CRC 
               
               
                   
               
               
                 117 
                 IPHQRSSL 
                 CLL 
               
               
                   
               
               
                 118 
                 NPERHKPSF 
                 AML 
               
               
                   
               
               
                 119 
                 KATEYVHSL 
                 CRC, UEC 
               
               
                   
               
               
                 120 
                 TVRPKNAAL 
                 AML, HCC, OSCAR, UEC 
               
               
                   
               
               
                 121 
                 GPFQRAAL 
                 UEC 
               
               
                   
               
               
                 122 
                 KPRTPFTTAQLL 
                 UEC 
               
               
                   
               
               
                 123 
                 RPRLRDLPAL 
                 CLL, GBC, NHL, OC, OSCAR, RCC 
               
               
                   
               
               
                 124 
                 KTIDGHINL 
                 CRC, NSCLCadeno, NSCLCother 
               
               
                   
               
               
                 125 
                 SPAKQFNIY 
                 SCLC 
               
               
                   
               
               
                 126 
                 MPREDAHF 
                 MEL 
               
               
                   
               
               
                 127 
                 KSKQVITLL 
                 NSCLCsquam 
               
               
                   
               
               
                 128 
                 SPPATLFLFLL 
                 OSCAR 
               
               
                   
               
               
                 129 
                 MTLPATTLTL 
                 BRCA, CCC, CLL, CRC, 
               
               
                   
                   
                 GBC, GBM, HCC, HNSCC, 
               
               
                   
                   
                 MEL, NSCLCadeno, NSCLCsquam, OC, OSCAR, 
               
               
                   
                   
                 PACA, RCC, SCLC, UBC, UEC 
               
               
                   
               
               
                 130 
                 GAYDKARYL 
                 BRCA 
               
               
                   
               
               
                 131 
                 MPFRNIRSIL 
                 HCC 
               
               
                   
               
               
                 132 
                 LPRLPVGSLV 
                 GC 
               
               
                   
               
               
                 133 
                 LPELPTTLTF 
                 NSCLCadeno 
               
               
                   
               
               
                 134 
                 VAAAARLTL 
                 MEL 
               
               
                   
               
               
                 135 
                 MPRLLRLSL 
                 UEC 
               
               
                   
               
               
                 136 
                 QPDHAGIFRVF 
                 HNSCC, OSCAR 
               
               
                   
               
               
                 137 
                 SPQLSYFEY 
                 OSCAR 
               
               
                   
               
               
                 138 
                 VPFNLITEY 
                 MEL 
               
               
                   
               
               
                 139 
                 LVILQHQAM 
                 RCC 
               
               
                   
               
               
                 140 
                 TPFPDIHWF 
                 NSCLCsquam, RCC, SCLC 
               
               
                   
               
               
                 141 
                 YGPYGSGSGW 
                 GC 
               
               
                   
               
               
                 142 
                 HPFKMKWQY 
                 RCC 
               
               
                   
               
               
                 143 
                 YPMIPPAQL 
                 SCLC 
               
               
                   
               
               
                 144 
                 RPVQGIPTY 
                 MEL 
               
               
                   
               
               
                 145 
                 VPAQRLGLLL 
                 BRCA, GBM, HNSCC, NSCLCsquam, OC 
               
               
                   
               
               
                 146 
                 SPTRGSEF 
                 GBM 
               
               
                   
               
               
                 147 
                 HVAQPAVVL 
                 BRCA, HCC 
               
               
                   
               
               
                 148 
                 KPHLIYRQ 
                 AML, BRCA, CRC, HCC, HNSCC, MEL, NSCLCadeno, 
               
               
                   
                   
                 OSCAR, RCC, SCLC, UEC 
               
               
                   
               
               
                 149 
                 SPSSVFTSK 
                 BRCA 
               
               
                   
               
               
                 150 
                 APLHGGGSL 
                 PRCA 
               
               
                   
               
               
                 151 
                 QPTWNTQTRL 
                 NHL 
               
               
                   
               
               
                 152 
                 SSASFSSELFRH 
                 BRCA, CCC, OSCAR, PACA, SCLC, UEC 
               
               
                   
               
               
                 153 
                 QPVHSLCSA 
                 GC 
               
               
                   
               
               
                 154 
                 RPPPSRRAVL 
                 GBM 
               
               
                   
               
               
                 155 
                 APIPRLIEG 
                 OSCAR 
               
               
                   
               
               
                 156 
                 GSRPVTGSV 
                 BRCA 
               
               
                   
               
               
                 157 
                 RPVTGSVC 
                 BRCA, NSCLCadeno 
               
               
                   
               
               
                 158 
                 SVPVATVEL 
                 CLL 
               
               
                   
               
               
                 159 
                 TPMTVPRI 
                 CLL, NHL 
               
               
                   
               
               
                 160 
                 IPVSHPVLTF 
                 BRCA, CRC, GBM, HCC, NSCLCadeno 
               
               
                   
               
               
                 161 
                 ASKILETSL 
                 MEL 
               
               
                   
               
               
                 163 
                 FRYPNGVSL 
                 HCC 
               
               
                   
               
               
                 164 
                 RAAGRRLQL 
                 HCC 
               
               
                   
               
               
                 166 
                 YAYTSRVIL 
                 NHL 
               
               
                   
               
               
                 167 
                 NVNPARKGL 
                 AML 
               
               
                   
               
               
                 168 
                 SPSGQRDVSL 
                 MEL 
               
               
                   
               
               
                 169 
                 RPFSVSSISQL 
                 MEL 
               
               
                   
               
               
                 170 
                 APEGKRLGF 
                 MEL 
               
               
                   
               
               
                 171 
                 LPLGGHKSL 
                 MEL 
               
               
                   
               
               
                 172 
                 SAQSLHPVL 
                 GBM 
               
               
                   
               
               
                 173 
                 VIINNPISL 
                 NSCLCother 
               
               
                   
               
               
                 174 
                 IPVTSSVTL 
                 NSCLCsquam, OSCAR 
               
               
                   
               
               
                 175 
                 AAFPHKIIF 
                 OSCAR 
               
               
                   
               
               
                 176 
                 QPLDICHSF 
                 OC 
               
               
                   
               
               
                 177 
                 VWEPQGSSRSL 
                 UEC 
               
               
                   
               
               
                 178 
                 VPYYPRANL 
                 OSCAR 
               
               
                   
               
               
                 179 
                 PRVRLLLL 
                 GBC, HNSCC 
               
               
                   
               
               
                 180 
                 RLRDYISSL 
                 CLL, NHL 
               
               
                   
               
               
                 181 
                 LPVSPARAL 
                 HNSCC, NSCLCadeno, NSCLCsquam, OSCAR 
               
               
                   
               
               
                 182 
                 RPLPVSPARAL 
                 BRCA, NSCLCadeno, NSCLCsquam 
               
               
                   
               
               
                 183 
                 VPRRPARAL 
                 BRCA, GBM, MEL 
               
               
                   
               
               
                 184 
                 KIIASGNHL 
                 NSCLCother 
               
               
                   
               
               
                 185 
                 RPVLTASSF 
                 NHL 
               
               
                   
               
               
                 188 
                 HAAASFETL 
                 NSCLCadeno 
               
               
                   
               
               
                 189 
                 QPQCSTHIL 
                 CCC, HCC, OSCAR 
               
               
                   
               
               
                 190 
                 RLAHVRARL 
                 UEC 
               
               
                   
               
               
                 191 
                 KPKAVKPKAA 
                 NSCLCadeno 
               
               
                   
               
               
                 192 
                 IPFADVKSF 
                 NSCLCadeno, NSCLCsquam, SCLC 
               
               
                   
               
               
                 193 
                 LPALKEEAF 
                 PRCA 
               
               
                   
               
               
                 194 
                 HPNKIKASL 
                 BRCA 
               
               
                   
               
               
                 195 
                 NPIFGRKEL 
                 UEC 
               
               
                   
               
               
                 196 
                 RPSGTAGAAL 
                 HNSCC, NSCLCsquam, RCC 
               
               
                   
               
               
                 197 
                 RPSGTAGAALLA 
                 HCC 
               
               
                   
               
               
                 198 
                 LPSPAHAFRAL 
                 OC 
               
               
                   
               
               
                 199 
                 SPFWIHQA 
                 AML 
               
               
                   
               
               
                 200 
                 EPFHLIVSY 
                 CRC, HNSCC, MEL, 
               
               
                   
                   
                 NSCLCadeno, NSCLCsquam, 
               
               
                   
                   
                 OSCAR, RCC, SCLC 
               
               
                   
               
               
                 201 
                 LPIARVLTV 
                 UEC 
               
               
                   
               
               
                 202 
                 SPSREASAL 
                 CLL, GBM, UBC 
               
               
                   
               
               
                 203 
                 KPRGPIDI 
                 CRC, GBC, NSCLCadeno 
               
               
                   
               
               
                 204 
                 FPYSGDKILV 
                 AML, CRC, GC, HCC, 
               
               
                   
                   
                 MEL, NSCLCsquam, PACA, 
               
               
                   
                   
                 SCLC, UBC, UEC 
               
               
                   
               
               
                 205 
                 LPPALLTTV 
                 GC 
               
               
                   
               
               
                 206 
                 TPRIGPKVSL 
                 AML, BRCA, CCC, CLL, 
               
               
                   
                   
                 CRC, GBC, GBM, GC, HCC, 
               
               
                   
                   
                 HNSCC, MEL, NSCLCadeno, NSCLCsquam, OSCAR, 
               
               
                   
                   
                 PACA, RCC, SCLC, UBC, UEC 
               
               
                   
               
               
                 207 
                 VPSDITTAF 
                 NSCLCadeno, OSCAR, SCLC 
               
               
                   
               
               
                 208 
                 RNRQVATAL 
                 CCC, CRC, GBC, HNSCC 
               
               
                   
               
               
                 209 
                 KIEQIRAVL 
                 OSCAR 
               
               
                   
               
               
                 210 
                 IPENRVVSY 
                 OSCAR 
               
               
                   
               
               
                 211 
                 IPDTIASVL 
                 MEL 
               
               
                   
               
               
                 212 
                 VPYAAQAAL 
                 BRCA 
               
               
                   
               
               
                 214 
                 LPLKFFPII 
                 UEC 
               
               
                   
               
               
                 215 
                 IPVAIKEL 
                 NSCLCother 
               
               
                   
               
               
                 216 
                 LPWEQNEQV 
                 HCC 
               
               
                   
               
               
                 217 
                 SPGDKRLAAYL 
                 CCC, HCC 
               
               
                   
               
               
                 218 
                 VQRTPPPI 
                 GC, NSCLCadeno, NSCLCsquam, OSCAR 
               
               
                   
               
               
                 219 
                 VPHTGRYTCL 
                 RCC 
               
               
                   
               
               
                 220 
                 RPAPGPAPFV 
                 BRCA 
               
               
                   
               
               
                 221 
                 LPQRPNARL 
                 CCC, CRC, GBC, GC, HCC, HNSCC, MEL, 
               
               
                   
                   
                 NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, 
               
               
                   
                   
                 PRCA, RCC, SCLC, UBC, UEC 
               
               
                   
               
               
                 222 
                 MLKTTLTAF 
                 HCC 
               
               
                   
               
               
                 223 
                 KAHVRIEL 
                 CRC 
               
               
                   
               
               
                 226 
                 APGGSSRSSL 
                 AML 
               
               
                   
               
               
                 229 
                 FPNAGPRHLL 
                 AML, CLL, NHL, OC, RCC 
               
               
                   
               
               
                 230 
                 DVIDDIISL 
                 GBM, HCC, HNSCC, NHL, NSCLCsquam 
               
               
                   
               
               
                 231 
                 SPITLQAL 
                 HCC 
               
               
                   
               
               
                 232 
                 TAYPSLRLL 
                 BRCA, HCC, MEL, NHL, 
               
               
                   
                   
                 NSCLCadeno, NSCLCsquam, 
               
               
                   
                   
                 PACA, SCLC, UEC 
               
               
                   
               
               
                 233 
                 MAYDRFIAI 
                 CRC, GBC, NSCLCadeno, RCC 
               
               
                   
               
               
                 234 
                 HPRAPGEQQRL 
                 BRCA, CRC, UEC 
               
               
                   
               
               
                 235 
                 AQNPAGTAL 
                 MEL 
               
               
                   
               
               
                 236 
                 TPELKSSIL 
                 HCC 
               
               
                   
               
               
                 237 
                 LPRAGGAF 
                 GBC, GC, NSCLCadeno, PACA, RCC 
               
               
                   
               
               
                 238 
                 LPRAGGAFLM 
                 HNSCC 
               
               
                   
               
               
                 239 
                 VLPRAGGAFLM 
                 NSCLCadeno 
               
               
                   
               
               
                 241 
                 LPKAALLV 
                 CLL 
               
               
                   
               
               
                 242 
                 IPETASVVAI 
                 AML, CCC, CRC, 
               
               
                   
                   
                 NSCLCadeno, NSCLCsquam 
               
               
                   
               
               
                 243 
                 MARTGGMVVI 
                 CRC, NSCLCadeno, NSCLCsquam 
               
               
                   
               
               
                 244 
                 VPAHLVAA 
                 GC 
               
               
                   
               
               
                 245 
                 GPVPSPLAL 
                 OC 
               
               
                   
               
               
                 246 
                 RPILKEQSSSSF 
                 GBC, HNSCC, NSCLCsquam, OSCAR 
               
               
                   
               
               
                 247 
                 SPVGVGQRL 
                 SCLC 
               
               
                   
               
               
                 249 
                 SPRSGVLL 
                 OSCAR, UEC 
               
               
                   
               
               
                 250 
                 APAAPAAVPS 
                 CRC, GBM, OC 
               
               
                   
               
               
                 251 
                 MPVDSFNSM 
                 MEL, NSCLCadeno, NSCLCsquam, 
               
               
                   
                   
                 RCC, SCLC, UBC 
               
               
                   
               
               
                 252 
                 QPENSLEGISL 
                 NSCLCsquam 
               
               
                   
               
               
                 253 
                 MPVDSFNSML 
                 CRC, MEL, NSCLCsquam, SCLC, UBC 
               
               
                   
               
               
                 254 
                 RVIQGTTTL 
                 HCC 
               
               
                   
               
               
                 255 
                 VPSHWMVAL 
                 NHL 
               
               
                   
               
               
                 256 
                 SPVPSHWMVAL 
                 CLL, NHL 
               
               
                   
               
               
                 257 
                 APYGTLRKS 
                 MEL 
               
               
                   
               
               
                 258 
                 SVIGPNSRL 
                 SCLC 
               
               
                   
               
               
                 259 
                 VPMPGVQAV 
                 UEC 
               
               
                   
               
               
                 260 
                 LVQSSRSEV 
                 HNSCC, OSCAR 
               
               
                   
               
               
                 261 
                 SPSTSRTPL 
                 GBC, GBM, HCC, HNSCC, NSCLCadeno 
               
               
                   
               
               
                 262 
                 SPSTSRTPLLSSL 
                 BRCA, CCC, GBC, GBM, HCC, 
               
               
                   
                   
                 HNSCC, NHL, OSCAR, 
               
               
                   
                   
                 RCC, UEC 
               
               
                   
               
               
                 263 
                 SQRPPATSQA 
                 AML, BRCA, CCC, CLL, CRC, 
               
               
                   
                   
                 GBM, HCC, HNSCC, 
               
               
                   
                   
                 NHL, OC, OSCAR, PACA, PRCA, RCC 
               
               
                   
               
               
                 264 
                 APRPGNWIL 
                 MEL, NSCLCsquam 
               
               
                   
               
               
                 266 
                 KPYEGRVEI 
                 CLL, GBM 
               
               
                   
               
               
                 267 
                 MPVPGILL 
                 MEL 
               
               
                   
               
               
                 268 
                 EPLSVTASY 
                 HNSCC 
               
               
                   
               
               
                 269 
                 FTVSSSSAM 
                 GBC 
               
               
                   
               
               
                 270 
                 SPRGTTSTL 
                 CCC, CRC, GBC, HCC, NHL 
               
               
                   
               
               
                 271 
                 SPTPVFTTL 
                 CRC, GBC 
               
               
                   
               
               
                 272 
                 SSPRGTTSTL 
                 GBC, OSCAR 
               
               
                   
               
               
                 273 
                 TDTPSTTPTTI 
                 CCC, CRC, GBC, GBM, 
               
               
                   
                   
                 HCC, MEL, NSCLCadeno, 
               
               
                   
                   
                 OSCAR, PACA, PRCA, RCC, SCLC, UEC 
               
               
                   
               
               
                 274 
                 KPIRTGISPLAL 
                 CCC, HCC 
               
               
                   
               
               
                 276 
                 RPVWDVRSA 
                 HNSCC 
               
               
                   
               
               
                 277 
                 MPPLLIVAF 
                 OC 
               
               
                   
               
               
                 278 
                 LIAARGSLVL 
                 AML, CRC, MEL, NSCLCadeno, 
               
               
                   
                   
                 OSCAR, SCLC, UEC 
               
               
                   
               
               
                 279 
                 APADEPRTVL 
                 NSCLCsquam 
               
               
                   
               
               
                 280 
                 LPRAFLQSL 
                 CRC, NHL, NSCLCsquam 
               
               
                   
               
               
                 281 
                 NPRSPPATM 
                 AML, OC 
               
               
                   
               
               
                 282 
                 AVRLPTPNL 
                 AML 
               
               
                   
               
               
                 284 
                 RPSAPRGPP 
                 CRC, OSCAR 
               
               
                   
               
               
                 285 
                 RITWKGLLL 
                 NSCLCother 
               
               
                   
               
               
                 286 
                 APARPAAAF 
                 BRCA, MEL, NSCLCadeno, OC, RCC 
               
               
                   
               
               
                 287 
                 SPIPRPLFL 
                 BRCA 
               
               
                   
               
               
                 288 
                 LHAMNSLSAM 
                 NHL 
               
               
                   
               
               
                 289 
                 LPYEKVSRL 
                 CCC, NHL 
               
               
                   
               
               
                 291 
                 SPSKSLEM 
                 CRC 
               
               
                   
               
               
                 292 
                 LPMTHRLQL 
                 MEL 
               
               
                   
               
               
                 293 
                 FPYDKPLIM 
                 GC, NSCLCadeno 
               
               
                   
               
               
                 296 
                 SPLLMQRTL 
                 CLL, NHL 
               
               
                   
               
               
                 297 
                 FPIKYVNDF 
                 RCC 
               
               
                   
               
               
                 298 
                 RVLLRWISL 
                 GBM 
               
               
                   
               
               
                 299 
                 SPFSGGPVSF 
                 RCC 
               
               
                   
               
               
                 300 
                 HPYSDLADVF 
                 MEL 
               
               
                   
               
               
                 301 
                 FPAFLEAM 
                 MEL 
               
               
                   
               
               
                 302 
                 IPIDQILNSF 
                 MEL 
               
               
                   
               
               
                 303 
                 RPPPPCIAL 
                 MEL 
               
               
                   
               
               
                 304 
                 SPLIGDFPAF 
                 MEL 
               
               
                   
               
               
                 305 
                 AASPVGSAL 
                 HCC 
               
               
                   
               
               
                 306 
                 RPFPLALL 
                 CRC 
               
               
                   
               
               
                 307 
                 RPHQKGWLSI 
                 HCC 
               
               
                   
               
               
                 308 
                 RPDVVRTLL 
                 CRC, GBC, GC, HNSCC, MEL, NSCLCadeno, 
               
               
                   
                   
                 NSCLCsquam, OSCAR, PACA, RCC, UBC 
               
               
                   
               
               
                 311 
                 APRLALDPDAL 
                 BRCA, SCLC 
               
               
                   
               
               
                 312 
                 SPSLQSSRESL 
                 GBC, HNSCC, NSCLCadeno, NSCLCsquam, OSCAR, 
               
               
                   
                   
                 UBC 
               
               
                   
               
               
                 313 
                 VPLSSYVSI 
                 MEL 
               
               
                   
               
               
                 314 
                 IALMKLAGPL 
                 AML, CRC, HCC, MEL, NHL, NSCLCadeno, UEC 
               
               
                   
               
               
                 316 
                 NPREPEKSL 
                 BRCA, CRC, GBC, GC, HCC, OSCAR, SCLC 
               
               
                   
               
               
                 317 
                 MPYNSAHHCVV 
                 CLL, NHL 
               
               
                   
               
               
                 318 
                 TPISNTGVL 
                 AML, GBC, NHL, NSCLCadeno, NSCLCother, RCC 
               
               
                   
               
               
                 319 
                 RPLDTFRVL 
                 OSCAR 
               
               
                   
               
               
                 320 
                 APMHIDRNIL 
                 HCC 
               
               
                   
               
               
                 321 
                 QPQQPGFFL 
                 CLL 
               
               
                   
               
               
                 322 
                 RAVPVGSGL 
                 MEL, NSCLCadeno, NSCLCsquam 
               
               
                   
               
               
                 323 
                 TPHGITDIL 
                 CRC, UEC 
               
               
                   
               
               
                 324 
                 LPAPLRISL 
                 BRCA, GBM, MEL, NSCLCadeno, OC, UEC 
               
               
                   
               
               
                 325 
                 SPRSNPVRL 
                 NHL 
               
               
                   
               
               
                 326 
                 IPPFTQRVF 
                 OC 
               
               
                   
               
               
                 327 
                 GPRTTQSSVL 
                 NSCLCadeno 
               
               
                   
               
               
                 328 
                 LPLHRGDLVI 
                 CLL 
               
               
                   
               
               
                 329 
                 QPANFIVLL 
                 GBC 
               
               
                   
               
               
                 330 
                 RPFSAIAEL 
                 GBC 
               
               
                   
               
               
                 331 
                 SPDSAILKL 
                 NSCLCsquam, UEC 
               
               
                   
               
               
                 332 
                 SPYAGSTAF 
                 AML, NSCLCadeno 
               
               
                   
               
               
                 333 
                 SVLPRALSL 
                 BRCA 
               
               
                   
               
               
                 334 
                 YPLSLALHF 
                 OC 
               
               
                   
               
               
                 335 
                 VPPQNPRPSL 
                 AML, GBM, HNSCC, NHL, NSCLCadeno, OSCAR 
               
               
                   
               
               
                 336 
                 YPLQGPGLLSV 
                 NHL 
               
               
                   
               
               
                 337 
                 IPTSRVITL 
                 BRCA, CLL, HCC, MEL, NHL, NSCLCadeno, 
               
               
                   
                   
                 NSCLCsquam, OC, OSCAR, PACA, SCLC 
               
               
                   
               
               
                 338 
                 MPATPSLKV 
                 HNSCC, OC, PACA, UBC 
               
               
                   
               
               
                 339 
                 GPQRTTSV 
                 CCC 
               
               
                   
               
               
                 340 
                 APEPRAALL 
                 MEL, NSCLCsquam, OC 
               
               
                   
               
               
                 343 
                 RPRPPKVLGL 
                 AML, CCC, HCC, MEL, NSCLCadeno, NSCLCsquam, 
               
               
                   
                   
                 OC, OSCAR, RCC, SCLC, UEC 
               
               
                   
               
               
                 344 
                 VPYPSPTCV 
                 BRCA, HCC, UEC 
               
               
                   
               
               
                 345 
                 SAAPPGASL 
                 HCC 
               
               
                   
               
               
                 346 
                 IPMPRITWL 
                 BRCA 
               
               
                   
               
               
                 347 
                 SPLEKINSF 
                 GBC 
               
               
                   
               
               
                 348 
                 HPAPPVTSA 
                 OC 
               
               
                   
               
               
                 349 
                 QPRDGWPMML 
                 HNSCC, OSCAR 
               
               
                   
               
               
                 350 
                 RPKSTLMNF 
                 OC, OSCAR 
               
               
                   
               
               
                 351 
                 SPYADIIPSA 
                 HNSCC 
               
               
                   
               
               
                 352 
                 LPAFSKIGGIL 
                 CRC, MEL 
               
               
                   
               
               
                 353 
                 KPRATWTL 
                 AML, BRCA, CCC, CLL, GBC, GC, HCC, HNSCC, 
               
               
                   
                   
                 MEL, NSCLCadeno, NSCLCsquam, OC, OSCAR, 
               
               
                   
                   
                 PACA, RCC, SCLC, UEC 
               
               
                   
               
               
                 354 
                 APAKDARASL 
                 CRC, GBC, HNSCC, NSCLCadeno, NSCLCsquam, 
               
               
                   
                   
                 OC, OSCAR, UBC 
               
               
                   
               
               
                 355 
                 APKTSFIAA 
                 GC 
               
               
                   
               
               
                 356 
                 RPFLRLPSL 
                 CRC, HCC, HNSCC, OC, OSCAR 
               
               
                   
               
               
                 357 
                 LPPHIFAI 
                 CRC, GC, HCC, UEC 
               
               
                   
               
               
                 358 
                 APSMLRKNQL 
                 HCC 
               
               
                   
               
               
                 359 
                 SPRRLVELAGQSL 
                 MEL, OC, OSCAR, UEC 
               
               
                   
               
               
                 361 
                 SPYGSDRLVQL 
                 CLL, NHL 
               
               
                   
               
               
                 362 
                 KPMLPPAAF 
                 UEC 
               
               
                   
               
               
                 363 
                 KPRTPFTTA 
                 UEC 
               
               
                   
               
               
                 364 
                 KPRTPFTTAQL 
                 BRCA, CRC, GBM, RCC, UEC 
               
               
                   
               
               
                 365 
                 RPKHFLQML 
                 OSCAR 
               
               
                   
               
               
                 366 
                 SPTLRQLDL 
                 CCC, HCC 
               
               
                   
               
               
                 367 
                 APQVHIFSL 
                 BRCA, CRC, GBM, RCC, UEC 
               
               
                   
               
               
                 368 
                 NPASRLTAL 
                 BRCA, CCC, CRC, GBC, GBM, GC, HCC, HNSCC, 
               
               
                   
                   
                 MEL, NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR, 
               
               
                   
                   
                 PACA, PRCA, RCC, SCLC, UBC, UEC 
               
               
                   
               
               
                 370 
                 AAHEFGHVL 
                 BRCA, UEC 
               
               
                   
               
               
                 371 
                 APRSPGQVTPRGL 
                 NSCLCadeno, OC 
               
               
                   
               
               
                 372 
                 SPSSASLTL 
                 GBC, NSCLCsquam, OSCAR 
               
               
                   
               
               
                 373 
                 LPKPDLPQLI 
                 AML, BRCA, HCC, MEL, NSCLCadeno, PRCA, RCC, 
               
               
                   
                   
                 UEC 
               
               
                   
               
               
                 374 
                 KPRNMTGLDL 
                 CLL 
               
               
                   
               
               
                 375 
                 LPRGVLEGL 
                 CRC, NSCLCadeno, UEC 
               
               
                   
               
               
                 376 
                 FPQVGRTAL 
                 AML, BRCA, CCC, CLL, CRC, GBC, GC, HCC, 
               
               
                   
                   
                 HNSCC, MEL, NHL, NSCLCadeno, NSCLCother, 
               
               
                   
                   
                 NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC, 
               
               
                   
                   
                 SCLC, UBC, UEC 
               
               
                   
               
               
                 377 
                 SPFSKRIKL 
                 AML, BRCA, CLL, GC, HNSCC, MEL, NHL, 
               
               
                   
                   
                 NSCLCadeno, NSCLCsquam, OC, OSCAR, RCC, 
               
               
                   
                   
                 SCLC, UBC, UEC 
               
               
                   
               
               
                 379 
                 GPRQVLFPL 
                 AML, BRCA, CCC, CRC, GBC, GBM, GC, HCC, 
               
               
                   
                   
                 HNSCC, MEL, NHL, NSCLCadeno, NSCLCsquam, OC, 
               
               
                   
                   
                 OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 
               
               
                   
               
               
                 380 
                 SPYPGSAAF 
                 BRCA, NSCLCadeno, OSCAR 
               
               
                   
               
               
                 381 
                 APRPRLLLL 
                 AML, BRCA, CCC, CLL, CRC, GBC, GBM, GC, HCC, 
               
               
                   
                   
                 HNSCC, MEL, NHL, NSCLCadeno, NSCLCother, 
               
               
                   
                   
                 NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC, 
               
               
                   
                   
                 SCLC, UBC, UEC 
               
               
                   
               
               
                 382 
                 RPGPQRTTSV 
                 BRCA, CCC, CLL, HCC, MEL, NHL, OC, OSCAR, 
               
               
                   
                   
                 PRCA, SCLC, UEC 
               
               
                   
               
               
                 383 
                 KPRATWTLKL 
                 BRCA, CCC, CRC, GBC, GC, HCC, HNSCC, MEL, 
               
               
                   
                   
                 NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR, RCC, 
               
               
                   
                   
                 SCLC, UEC 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8b 
               
             
            
               
                   
               
               
                 Overview of presentation of selected tumor- 
               
               
                 associated peptides of the present 
               
               
                 invention across entities. 
               
               
                 AML: acute myeloid leukemia; 
               
               
                 BRCA: breast cancer; 
               
               
                 CCC: cholangiocellular carcinoma; 
               
               
                 CLL: chronic lymphocytic leukemia; 
               
               
                 CRC: colorectal cancer; 
               
               
                 GBC: gallbladder cancer; 
               
               
                 GBM: glioblastoma; 
               
               
                 GC: gastric cancer; 
               
               
                 HCC: hepatocellular carcinoma; 
               
               
                 HNSCC: head and neck squamous 
               
               
                 cell carcinoma; 
               
               
                 MEL: melanoma; 
               
               
                 NHL: non-Hodgkin lymphoma; 
               
               
                 NSCLCadeno: non-small cell lung 
               
               
                 cancer adenocarcinoma; 
               
               
                 NSCLCother: NSCLC samples that could 
               
               
                 not unambiguously be assigned to 
               
               
                 NSCLCadeno or NSCLCsquam; 
               
               
                 NSCLCsquam: squamous cell non-small 
               
               
                 cell lung cancer; 
               
               
                 OC: ovarian cancer; 
               
               
                 OSCAR: esophageal cancer; 
               
               
                 PACA: pancreatic cancer; 
               
               
                 PRCA: prostate cancer; 
               
               
                 RCC: renal cell carcinoma; 
               
               
                 SCLC: small cell lung cancer; 
               
               
                 UBC: urinary bladder carcinoma; 
               
               
                 UEC: uterine and endometrial cancer. 
               
            
           
           
               
               
               
               
            
               
                   
                 SEQ ID 
                   
                 Peptide Presentation 
               
               
                   
                 No. 
                 Sequence 
                 on cancer entities 
               
               
                   
                   
               
               
                   
                 448 
                 TVYGEPRKL 
                 OSCAR 
               
               
                   
                   
               
               
                   
                 449 
                 RPKTSVNLISSL 
                 SCLC 
               
               
                   
                   
               
               
                   
                 450 
                 SAAARALLP 
                 CCC, CRC, GBM, GC, 
               
               
                   
                   
                   
                 HCC, NSCLCother, 
               
               
                   
                   
                   
                 NSCLCsquam, PACA, 
               
               
                   
                   
                   
                 SCLC, UEC 
               
               
                   
                   
               
               
                   
                 451 
                 VPILPLNHAL 
                 UEC 
               
               
                   
                   
               
               
                   
                 454 
                 SPDPAHLESL 
                 NSCLCother 
               
               
                   
                   
               
               
                   
                 455 
                 FPVQATIDF 
                 OC 
               
               
                   
                   
               
               
                   
                 456 
                 VPVSHPVLTL 
                 NSCLCsquam 
               
               
                   
                   
               
               
                   
                 457 
                 RPPLSQRHTF 
                 NHL 
               
               
                   
                   
               
               
                   
                 459 
                 SPAPWRPWI 
                 SCLC 
               
               
                   
                   
               
               
                   
                 460 
                 APLMPLGKTL 
                 PACA 
               
               
                   
                   
               
               
                   
                 461 
                 MPHLGPGILL 
                 MEL 
               
               
                   
                   
               
               
                   
                 462 
                 MPLLADVRL 
                 MEL 
               
               
                   
                   
               
               
                   
                 463 
                 LPTDLFNSVM 
                 MEL 
               
               
                   
                   
               
               
                   
                 467 
                 VPRNQDWLGVSR 
                 MEL 
               
               
                   
                   
                 QL 
                   
               
               
                   
                   
               
               
                   
                 468 
                 LPSLHVLVL 
                 MEL 
               
               
                   
                   
               
               
                   
                 469 
                 LPLDTRTSI 
                 CLL 
               
               
                   
                   
               
               
                   
                 470 
                 RPNGEVKSEL 
                 SCLC 
               
               
                   
                   
               
               
                   
                 471 
                 LPLLAGTLLL 
                 NSCLCadeno 
               
               
                   
                   
               
               
                   
                 472 
                 LPMPAITWY 
                 MEL 
               
               
                   
                   
               
               
                   
                 473 
                 LPGEREAAL 
                 MEL 
               
               
                   
                   
               
               
                   
                 474 
                 VPKADLLTL 
                 MEL 
               
               
                   
                   
               
               
                   
                 475 
                 IPLEIQKL 
                 MEL 
               
               
                   
                   
               
               
                   
                 476 
                 EPNPVEEIF 
                 NSCLCsquam 
               
               
                   
                   
               
               
                   
                 477 
                 NPVPVITWYKDNRL 
                 MEL 
               
               
                   
                   
               
               
                   
                 478 
                 APKFISPASQL 
                 SCLC 
               
               
                   
                   
               
               
                   
                 479 
                 APHAGGALL 
                 NSCLCsquam 
               
               
                   
                   
               
               
                   
                 480 
                 VPAAPTKAL 
                 CLL 
               
               
                   
                   
               
               
                   
                 481 
                 SPARALLLALA 
                 HNSCC 
               
               
                   
                   
               
               
                   
                 482 
                 QPSLKKIIL 
                 PACA 
               
               
                   
                   
               
               
                   
                 484 
                 LPASAEPKGTM 
                 HNSCC 
               
               
                   
                   
               
               
                   
                 485 
                 LPLKTKVFA 
                 NSCLCsquam 
               
               
                   
                   
               
               
                   
                 486 
                 TPTRPLPSA 
                 NSCLCadeno 
               
               
                   
                   
               
               
                   
                 487 
                 IPWFIKTAF 
                 MEL 
               
               
                   
                   
               
               
                   
                 488 
                 LPLGGLPLLI 
                 CLL 
               
               
                   
                   
               
               
                   
                 489 
                 WPNHIMLVL 
                 MEL 
               
               
                   
                   
               
               
                   
                 491 
                 MPEADLKRIF 
                 MEL 
               
               
                   
                   
               
               
                   
                 492 
                 IPFSVDEI 
                 NSCLCother, UEC 
               
               
                   
                   
               
               
                   
                 493 
                 LPLQQYKLV 
                 HCC 
               
               
                   
                   
               
               
                   
                 494 
                 LPLRAVNLNL 
                 SCLC 
               
               
                   
                   
               
               
                   
                 495 
                 SPSYTQASL 
                 BRCA 
               
               
                   
                   
               
               
                   
                 496 
                 MPAVSGPGPLF 
                 NSCLCadeno 
               
               
                   
                   
               
               
                   
                 497 
                 YVVKPLHPF 
                 CRC 
               
               
                   
                   
               
               
                   
                 498 
                 RPQPQPRPAL 
                 HNSCC, OSCAR 
               
               
                   
                   
               
               
                   
                 499 
                 QPVLPSPAC 
                 MEL 
               
               
                   
                   
               
            
           
         
       
     
     Example 2 
     Expression Profiling of Genes Encoding the Peptides of the Invention 
     Over-presentation or specific presentation of a peptide on tumor cells compared to normal cells is sufficient for its usefulness in immunotherapy, and some peptides are tumor-specific despite their source protein occurring also in normal tissues. Still, mRNA expression profiling adds an additional level of safety in selection of peptide targets for immunotherapies. Especially for therapeutic options with high safety risks, such as affinity-matured TCRs, the ideal target peptide will be derived from a protein that is unique to the tumor and not found on normal tissues. 
     RNA Sources and Preparation 
     Surgically removed tissue specimens were provided as indicated above (see Example 1) after written informed consent had been obtained from each patient. Tumor tissue specimens were snap-frozen immediately after surgery and later homogenized with mortar and pestle under liquid nitrogen. Total RNA was prepared from these samples using TRI Reagent (Ambion, Darmstadt, Germany) followed by a cleanup with RNeasy (QIAGEN, Hilden, Germany); both methods were performed according to the manufacturer&#39;s protocol. 
     Total RNA from healthy human tissues for RNASeq experiments was obtained from: Asterand (Detroit, Mich., USA &amp; Royston, Herts, UK); Bio-Options Inc. (Brea, Calif., USA); Geneticist Inc. (Glendale, Calif., USA); ProteoGenex Inc. (Culver City, Calif., USA); Tissue Solutions Ltd (Glasgow, UK). Total RNA from tumor tissues for RNASeq experiments was obtained from: Asterand (Detroit, Mich., USA &amp; Royston, Herts, UK); BioCat GmbH (Heidelberg, Germany); BioServe (Beltsville, Md., USA); Geneticist Inc. (Glendale, Calif., USA); Istituto Nazionale Tumori “Pascale” (Naples, Italy); ProteoGenex Inc. (Culver City, Calif., USA); University Hospital Heidelberg (Heidelberg, Germany). 
     Quality and quantity of all RNA samples were assessed on an Agilent 2100 Bioanalyzer (Agilent, Waldbronn, Germany) using the RNA 6000 Pico LabChip Kit (Agilent). 
     RNAseq Experiments 
     Gene expression analysis of—tumor and normal tissue RNA samples was performed by next generation sequencing (RNAseq) by CeGaT (Tübingen, Germany). Briefly, sequencing libraries are prepared using the Illumina HiSeq v4 reagent kit according to the provider&#39;s protocol (Illumina Inc., San Diego, Calif., USA), which includes RNA fragmentation, cDNA conversion and addition of sequencing adaptors. Libraries derived from multiple samples are mixed equimolar and sequenced on the Illumina HiSeq 2500 sequencer according to the manufacturer&#39;s instructions, generating 50 bp single end reads. Processed reads are mapped to the human genome (GRCh38) using the STAR software. Expression data are provided on transcript level as RPKM (Reads Per Kilobase per Million mapped reads, generated by the software Cufflinks) and on exon level (total reads, generated by the software Bedtools), based on annotations of the ensembl sequence database (Ensembl77). Exon reads are normalized for exon length and alignment size to obtain RPKM values. 
     Exemplary expression profiles of source genes of the present invention that are highly over-expressed or exclusively expressed in acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer are shown in  FIGS.  2 A- 2 T . Expression scores for further exemplary genes are shown in Table 9a and 9b. 
     
       
         
           
               
             
               
                 TABLE 9a 
               
             
            
               
                   
               
               
                 Expression scores. The table lists peptides from genes that are very highly 
               
               
                 over-expressed in tumors compared to a panel of normal tissues (+++), highly over- 
               
               
                 expressed in tumors compared to a panel of normal tissues (++) or over-expressed in 
               
               
                 tumors compared to a panel of normal tissues (+). The baseline for this score was 
               
               
                 calculated from measurements of the following relevant normal tissues: adipose tissue, 
               
               
                 adrenal gland, bile duct, blood cells, blood vessels, bone marrow, brain, esophagus, eye, 
               
               
                 gallbladder, heart, head &amp; neck, kidney, large intestine, liver, lung, lymph node, nerve, 
               
               
                 parathyroid, pancreas, pituitary, pleura, skeletal muscle, skin, small intestine, spleen, 
               
               
                 stomach, thyroid gland, trachea, ureter, urinary bladder. In case expression data for 
               
               
                 several samples of the same tissue type were available, the arithmetic mean of all 
               
               
                 respective samples was used for the calculation. AML: acute myeloid leukemia; BRCA: 
               
               
                 breast cancer; CCC: cholangiocellular carcinoma; CLL: chronic lymphocytic leukemia; 
               
               
                 CRC: colorectal cancer; GBC: gallbladder cancer; GBM: glioblastoma; GC: gastric 
               
               
                 cancer; HCC: hepatocellular carcinoma; HNSCC: head and neck squamous cell 
               
               
                 carcinoma; MEL: melanoma; NHL: non-Hodgkin lymphoma; NSCLCadeno: non-small cell 
               
               
                 lung cancer adenocarcinoma; NSCLCother: NSCLC samples that could not 
               
               
                 unambiguously be assigned to NSCLCadeno or NSCLCsquam; NSCLCsquam: 
               
               
                 squamous cell non-small cell lung cancer; OC: ovarian cancer; OSCAR: esophageal 
               
               
                 cancer; PACA: pancreatic cancer; PRCA: prostate cancer; RCC: renal cell carcinoma; 
               
               
                 SCLC: small cell lung cancer; UBC: urinary bladder carcinoma; UEC: uterine and 
               
               
                 endometrial cancer 
               
            
           
           
               
               
               
            
               
                   
                   
                 Gene Expression in tumor samples 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                   
                 very highly 
               
               
                 Seq 
                   
                   
                   
                 over- 
               
               
                 No 
                   
                   
                 highly over- 
                 expressed 
               
               
                 ID 
                 Sequence 
                 over-expressed (+) 
                 expressed (++) 
                 (+++) 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1 
                 RPRSLQCVSL 
                 CLL 
                   
                 PRCA 
               
               
                   
               
               
                 2 
                 VPGSDPARYEFL 
                 HCC, UEC 
                 GBC, GC, 
                 MEL, UBC 
               
               
                   
                   
                   
                 HNSCC, 
                   
               
               
                   
                   
                   
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 OC, OSCAR, 
                   
               
               
                   
                   
                   
                 SCLC 
                   
               
               
                   
               
               
                 3 
                 MPYVVLTAL 
                 NSCLCsquam, SCLC 
                 NSCLCadeno 
                 RCC 
               
               
                   
               
               
                 4 
                 GPKKFIVKL 
                   
                   
                 PRCA 
               
               
                   
               
               
                 5 
                 LPSLSHCSQL 
                 AML, BRCA, NHL, 
                 GBC, HNSCC, 
                 MEL, UEC 
               
               
                   
                   
                 OSCAR, UBC 
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 OC, RCC, 
                   
               
               
                   
                   
                   
                 SCLC 
                   
               
               
                   
               
               
                 6 
                 LPLNSSTSL 
                 BRCA, HCC, RCC 
                 CCC, CRC, 
                 GBC, 
               
               
                   
                   
                   
                 GC, HNSCC, 
                 NSCLCother, 
               
               
                   
                   
                   
                 MEL, NHL, 
                 NSCLCsquam, 
               
               
                   
                   
                   
                 NSCLCadeno, 
                 SCLC 
               
               
                   
                   
                   
                 OC, OSCAR, 
                   
               
               
                   
                   
                   
                 PACA, UBC, 
                   
               
               
                   
                   
                   
                 UEC 
                   
               
               
                   
               
               
                 7 
                 RPSQLAPATL 
                 AML, GC, HCC, 
                 GBC 
                 SCLC 
               
               
                   
                   
                 HNSCC, MEL, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, UBC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 8 
                 MPKTNLSKM 
                 AML, GC, HCC, 
                 GBC 
                 SCLC 
               
               
                   
                   
                 HNSCC, MEL, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, UBC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 9 
                 RPDSRLLEL 
                 GC, HNSCC, 
                 HCC, MEL, 
                 GBC 
               
               
                   
                   
                 NSCLCsquam, OC, 
                 SCLC 
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 10 
                 SPMEAELVRRIL 
                 GC, HNSCC, 
                 HCC, MEL, 
                 GBC 
               
               
                   
                   
                 NSCLCsquam, OC, 
                 SCLC 
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 11 
                 APLPRPGAV 
                 GC, HNSCC, 
                 HCC, MEL, 
                 GBC 
               
               
                   
                   
                 NSCLCsquam, OC, 
                 SCLC 
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 12 
                 LPNTGRIGQLL 
                   
                   
                 PRCA 
               
               
                   
               
               
                 13 
                 LPNTGRIGQL 
                   
                   
                 PRCA 
               
               
                   
               
               
                 14 
                 AVHEIGHSL 
                 HCC, RCC 
                 CCC, GC, 
                 CRC, GBC, 
               
               
                   
                   
                   
                 MEL, NHL, 
                 HNSCC, 
               
               
                   
                   
                   
                 NSCLCadeno, 
                 NSCLCother, 
               
               
                   
                   
                   
                 OC, PACA, 
                 NSCLCsquam, 
               
               
                   
                   
                   
                 UEC 
                 OSCAR, 
               
               
                   
                   
                   
                   
                 SCLC, UBC 
               
               
                   
               
               
                 15 
                 KPGFNISIL 
                 OC 
                   
                 BRCA 
               
               
                   
               
               
                 16 
                 FPAPPAHWF 
                 OC 
                   
                 BRCA 
               
               
                   
               
               
                 17 
                 SPAAPLSPASSL 
                   
                   
                 UBC 
               
               
                   
               
               
                 18 
                 MALSVLRLAL 
                   
                   
                 AML 
               
               
                   
               
               
                 19 
                 WPRLPGAGL 
                 GC, HCC, 
                 GBC, HNSCC, 
                 MEL 
               
               
                   
                   
                 NSCLCsquam, PACA, 
                 OSCAR 
                   
               
               
                   
                   
                 SCLC, UBC, UEC 
                   
                   
               
               
                   
               
               
                 20 
                 MVLGIGPVL 
                   
                   
                 PRCA 
               
               
                   
               
               
                 21 
                 APSRLLEL 
                 CCC, CRC, GBC, MEL, 
                   
                 HCC 
               
               
                   
                   
                 SCLC 
                   
                   
               
               
                   
               
               
                 22 
                 LPQLKPAL 
                 BRCA, NSCLCsquam 
                 OSCAR 
                 HNSCC 
               
               
                   
               
               
                 23 
                 VPRPTSTVGL 
                   
                 MEL 
                   
               
               
                   
               
               
                 24 
                 VPRPTSTVGLFL 
                   
                 MEL 
                   
               
               
                   
               
               
                 25 
                 RPQGAVGGL 
                 GBC 
                 HCC 
                   
               
               
                   
               
               
                 26 
                 SPSFSSTLLSL 
                 BRCA, GBC, SCLC 
                 HCC, MEL 
                   
               
               
                   
               
               
                 27 
                 RIRVTSEVL 
                 HCC, MEL, UEC 
                 BRCA, PRCA 
                   
               
               
                   
               
               
                 28 
                 LPAPTSLVL 
                   
                 GBM 
                   
               
               
                   
               
               
                 29 
                 APLRVHITSL 
                 HCC 
                 CCC, 
                   
               
               
                   
                   
                   
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 OC 
                   
               
               
                   
               
               
                 30 
                 YPGFTKRL 
                 GC, HNSCC, MEL, 
                 BRCA, CCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 CRC, GBC, 
                   
               
               
                   
                   
                 NSCLCsquam, 
                 HCC, OC, UBC 
                   
               
               
                   
                   
                 OSCAR, PACA, RCC, 
                   
                   
               
               
                   
                   
                 SCLC 
                   
                   
               
               
                   
               
               
                 31 
                 RPGPSDPAA 
                 NSCLCadeno, UEC 
                 RCC 
                   
               
               
                   
               
               
                 32 
                 APMAPGRSPL 
                 BRCA 
                 UEC 
                   
               
               
                   
               
               
                 33 
                 LPRGLSPARQL 
                 BRCA 
                 UEC 
                   
               
               
                   
               
               
                 34 
                 APMAPGRSP 
                 BRCA 
                 UEC 
                   
               
               
                   
               
               
                 35 
                 APLPPPRAL 
                   
                 GBM 
                   
               
               
                   
               
               
                 36 
                 RPFSREMDL 
                   
                 AML 
                   
               
               
                   
               
               
                 37 
                 LPPPRALTL 
                   
                 GBM 
                   
               
               
                   
               
               
                 38 
                 RPSFPNLTSF 
                   
                 AML 
                   
               
               
                   
               
               
                 39 
                 QPRPSSEKI 
                 AML, GBM 
                 SCLC 
                   
               
               
                   
               
               
                 40 
                 FPRTVKHIDAAL 
                 CRC, GC, 
                 HNSCC, 
                   
               
               
                   
                   
                 NSCLCadeno, PACA, 
                 NSCLCsquam, 
                   
               
               
                   
                   
                 UBC 
                 OSCAR 
                   
               
               
                   
               
               
                 41 
                 MPAGGGPRSL 
                 CCC, HCC, NHL, UEC 
                 CLL 
                   
               
               
                   
               
               
                 42 
                 APLKMLAL 
                   
                 NHL 
                   
               
               
                   
               
               
                 43 
                 APTPRPKVL 
                 PRCA, UEC 
                 BRCA 
                   
               
               
                   
               
               
                 44 
                 SPSQTVQRAV 
                   
                 NHL 
                   
               
               
                   
               
               
                 45 
                 TRPWSGPYIL 
                   
                 MEL 
                   
               
               
                   
               
               
                 46 
                 QPISGNPVTL 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 47 
                 RPRQTGALM 
                   
                 AML 
                   
               
               
                   
               
               
                 48 
                 RPRYSIGL 
                 PRCA, UEC 
                 BRCA 
                   
               
               
                   
               
               
                 49 
                 APEKARAFL 
                 GBC, HCC, HNSCC, 
                 CRC, GC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 PRCA 
                   
               
               
                   
                   
                 NSCLCother, SCLC, 
                   
                   
               
               
                   
                   
                 UBC, UEC 
                   
                   
               
               
                   
               
               
                 50 
                 PEKARAFL 
                 GBC, HCC, HNSCC, 
                 CRC, GC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 PRCA 
                   
               
               
                   
                   
                 NSCLCother, SCLC, 
                   
                   
               
               
                   
                   
                 UBC, UEC 
                   
                   
               
               
                   
               
               
                 51 
                 SPVFYVQTL 
                 HCC 
                 BRCA, PRCA 
                   
               
               
                   
               
               
                 52 
                 KEDNPSGHTYTL 
                 BRCA, MEL, 
                 GBC, HCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 NHL 
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 SCLC 
                   
                   
               
               
                   
               
               
                 53 
                 SPRIPFSTF 
                   
                 MEL 
                   
               
               
                   
               
               
                 54 
                 VPSCGRSVEGL 
                 CCC, NSCLCother, 
                 HNSCC, 
                   
               
               
                   
                   
                 UBC 
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 OSCAR, RCC 
                   
               
               
                   
               
               
                 55 
                 LPALLRSGL 
                 GBC, NHL, OSCAR 
                 CCC 
                   
               
               
                   
               
               
                 56 
                 LPALLRSGLTL 
                 GBC, NHL, OSCAR 
                 CCC 
                   
               
               
                   
               
               
                 57 
                 APLLPIRTL 
                   
                 UBC 
                   
               
               
                   
               
               
                 58 
                 APLLPIRTLPL 
                   
                 UBC 
                   
               
               
                   
               
               
                 59 
                 KPRTIYSSL 
                 HNSCC, NSCLCsquam 
                 SCLC, UEC 
                   
               
               
                   
               
               
                 60 
                 RPYSIYPHGVTF 
                 CCC 
                 HCC 
                   
               
               
                   
               
               
                 61 
                 LPRIPFSTF 
                   
                 MEL 
                   
               
               
                   
               
               
                 62 
                 KPQSTISGL 
                 CCC 
                 HCC 
                   
               
               
                   
               
               
                 63 
                 FPHMATTAF 
                 NSCLCother, OSCAR 
                 HNSCC 
                   
               
               
                   
               
               
                 64 
                 VPRPIFSQLYL 
                 HCC, OC, SCLC, UEC 
                 BRCA, PRCA 
                   
               
               
                   
               
               
                 65 
                 FPNVYSTLVL 
                 HCC 
                 MEL 
                   
               
               
                   
               
               
                 66 
                 LPMTVISVL 
                 PACA, UEC 
                 GC 
                   
               
               
                   
               
               
                 67 
                 VPVSRPVL 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 68 
                 FPNEVSVVL 
                 NSCLCadeno 
                 MEL 
                   
               
               
                   
               
               
                 69 
                 RPEDGRPRL 
                 SCLC 
                 GBM 
                   
               
               
                   
               
               
                 70 
                 VPAQRLGLL 
                 NSCLCother 
                 CLL 
                   
               
               
                   
               
               
                 71 
                 APFAPLHGGGSL 
                   
                 PRCA 
                   
               
               
                   
               
               
                 72 
                 APCNGNVAV 
                 BRCA, GBC, MEL, OC 
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 UBC 
                   
               
               
                   
               
               
                 73 
                 LPVSSPVTL 
                   
                 GBM 
                   
               
               
                   
               
               
                 74 
                 VPVSHPVL 
                   
                 CLL, NHL 
                   
               
               
                   
               
               
                 75 
                 HVRPQTNCI 
                 HCC, NSCLCother, 
                 GBM 
                   
               
               
                   
                   
                 NSCLCsquam, SCLC 
                   
                   
               
               
                   
               
               
                 76 
                 KPKVESQAL 
                 PRCA 
                 BRCA 
                   
               
               
                   
               
               
                 77 
                 QPRLVPGETL 
                   
                 MEL 
                   
               
               
                   
               
               
                 78 
                 HPSQESPTL 
                 SCLC 
                 UEC 
                   
               
               
                   
               
               
                 79 
                 GPASDHPSL 
                 BRCA, HCC, OC, UEC 
                 PRCA 
                   
               
               
                   
               
               
                 80 
                 SALPTTISF 
                 BRCA, CRC, GC, UEC 
                 HCC, 
                 GBC, 
               
               
                   
                   
                   
                 NSCLCadeno 
                 HNSCC, 
               
               
                   
                   
                   
                   
                 MEL, 
               
               
                   
                   
                   
                   
                 NSCLCsquam, 
               
               
                   
                   
                   
                   
                 OC, 
               
               
                   
                   
                   
                   
                 OSCAR, 
               
               
                   
                   
                   
                   
                 SCLC, UBC 
               
               
                   
               
               
                 81 
                 IAYPSLREAAL 
                 BRCA, CRC, GC, UEC 
                 HCC, 
                 GBC, 
               
               
                   
                   
                   
                 NSCLCadeno 
                 HNSCC, 
               
               
                   
                   
                   
                   
                 MEL, 
               
               
                   
                   
                   
                   
                 NSCLCsquam, 
               
               
                   
                   
                   
                   
                 OC, 
               
               
                   
                   
                   
                   
                 OSCAR, 
               
               
                   
                   
                   
                   
                 SCLC, UBC 
               
               
                   
               
               
                 82 
                 DAAHPGPSV 
                   
                 OC 
                 UEC 
               
               
                   
               
               
                 83 
                 AVSSHHNVI 
                 BRCA, GBC, HCC, 
                   
                 PRCA 
               
               
                   
                   
                 NHL, OC, SCLC, UBC 
                   
                   
               
               
                   
               
               
                 84 
                 MPMQDIKMI 
                 AML, BRCA, GC, NHL, 
                 GBC, HNSCC, 
                 MEL, OC, 
               
               
                   
                   
                 OSCAR, UBC 
                 NSCLCadeno, 
                 SCLC, UEC 
               
               
                   
                   
                   
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 RCC 
                   
               
               
                   
               
               
                 85 
                 MPMQDIKMILKM 
                 AML, BRCA, GC, NHL, 
                 GBC, HNSCC, 
                 MEL, OC, 
               
               
                   
                   
                 OSCAR, UBC 
                 NSCLCadeno, 
                 SCLC, UEC 
               
               
                   
                   
                   
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 RCC 
                   
               
               
                   
               
               
                 86 
                 ALLLRGVTL 
                 NSCLCsquam, SCLC 
                 NSCLCadeno 
                 RCC 
               
               
                   
               
               
                 87 
                 APVGGNVTSSF 
                 AML, HCC, HNSCC, 
                 GBC, NHL 
                 NSCLCsquam, 
               
               
                   
                   
                 MEL, OSCAR 
                   
                 OC 
               
               
                   
               
               
                 88 
                 KPSAVKDSIY 
                 OC 
                 PRCA, SCLC 
                 UEC 
               
               
                   
               
               
                 89 
                 FLIPRAGWLAGL 
                   
                   
                 PRCA 
               
               
                   
               
               
                 90 
                 HAIEKAFQL 
                 CRC, MEL, 
                 GC, 
                 HNSCC 
               
               
                   
                   
                 NSCLCadeno, PACA 
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 OSCAR, UBC 
                   
               
               
                   
               
               
                 91 
                 FPRLVGPDFF 
                 HCC, OC 
                 BRCA, CCC, 
                   
               
               
                   
                   
                   
                 CRC, GBC, 
                   
               
               
                   
                   
                   
                 GC, HNSCC, 
                   
               
               
                   
                   
                   
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 OSCAR, 
                   
               
               
                   
                   
                   
                 PACA, UBC, 
                   
               
               
                   
                   
                   
                 UEC 
                   
               
               
                   
               
               
                 92 
                 TSPLPPTV 
                   
                 RCC 
                   
               
               
                   
               
               
                 93 
                 SVAIAHGVF 
                 CRC 
                 SCLC 
                   
               
               
                   
               
               
                 94 
                 LPMSKRQEY 
                 BRCA, CRC, 
                 SCLC, UEC 
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, UBC 
                   
                   
               
               
                   
               
               
                 95 
                 RTKEEINEL 
                 HNSCC, NSCLCother, 
                 BRCA, GBC, 
                   
               
               
                   
                   
                 NSCLCsquam, PACA, 
                 MEL, 
                   
               
               
                   
                   
                 SCLC 
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 OC, UBC 
                   
               
               
                   
               
               
                 96 
                 QPSLVQAIF 
                 MEL 
                 AML 
                   
               
               
                   
               
               
                 97 
                 LPPGTQIQI 
                 SCLC 
                 GBM 
                   
               
               
                   
               
               
                 98 
                 FPCSALLACF 
                 BRCA 
                 RCC 
                   
               
               
                   
               
               
                 99 
                 MPVSAFTVI 
                 CRC, NSCLCsquam, 
                 BRCA, CCC, 
                   
               
               
                   
                   
                 OC, UBC, UEC 
                 GBC, GC, 
                   
               
               
                   
                   
                   
                 HNSCC, 
                   
               
               
                   
                   
                   
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 OSCAR, PACA 
                   
               
               
                   
               
               
                 100 
                 TPIPFDKILY 
                 CRC, NSCLCsquam, 
                 BRCA, CCC, 
                   
               
               
                   
                   
                 OC, UBC, UEC 
                 GBC, GC, 
                   
               
               
                   
                   
                   
                 HNSCC, 
                   
               
               
                   
                   
                   
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 OSCAR, PACA 
                   
               
               
                   
               
               
                 101 
                 KPGLPGLK 
                 CRC, NSCLCsquam, 
                 BRCA, CCC, 
                   
               
               
                   
                   
                 OC, UBC, UEC 
                 GBC, GC, 
                   
               
               
                   
                   
                   
                 HNSCC, 
                   
               
               
                   
                   
                   
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 OSCAR, PACA 
                   
               
               
                   
               
               
                 102 
                 MAGPAIHTAPM 
                 SCLC 
                 GBM 
                   
               
               
                   
               
               
                 103 
                 REPIMKADML 
                 BRCA, MEL, 
                 GBC, HCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 NHL 
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 SCLC 
                   
                   
               
               
                   
               
               
                 104 
                 RPLPNSVIHV 
                   
                 HCC 
                   
               
               
                   
               
               
                 105 
                 RPRYETGVCA 
                 CRC, GC, PACA 
                 HNSCC, MEL, 
                   
               
               
                   
                   
                   
                 OC, OSCAR, 
                   
               
               
                   
                   
                   
                 UBC 
                   
               
               
                   
               
               
                 106 
                 APFHIDRLF 
                 NSCLCsquam, PACA, 
                 GC 
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 107 
                 GQRLESPGGAA 
                 GBM 
                 SCLC 
                   
               
               
                   
               
               
                 108 
                 APRGSPPI 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 109 
                 LPRALMRST 
                   
                 NHL 
                   
               
               
                   
               
               
                 110 
                 YPSSPASAV 
                   
                 HCC 
                   
               
               
                   
               
               
                 111 
                 YPLQQTNVY 
                 GBM 
                 RCC 
                   
               
               
                   
               
               
                 112 
                 YPSPLNKHSF 
                 GBM 
                 RCC 
                   
               
               
                   
               
               
                 113 
                 KPHLDRRGAVI 
                   
                 GBC, HCC 
                   
               
               
                   
               
               
                 114 
                 FVPPSGPSNPM 
                   
                 MEL 
                   
               
               
                   
               
               
                 115 
                 KTKSLAQQL 
                 GBC, GC, 
                 CCC, HNSCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 NSCLCsquam, 
                   
               
               
                   
                   
                 NSCLCother, PACA 
                 OSCAR, UBC 
                   
               
               
                   
               
               
                 116 
                 RSYQHSLRL 
                 GBC, GC, 
                 CCC, HNSCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 NSCLCsquam, 
                   
               
               
                   
                   
                 NSCLCother, PACA 
                 OSCAR, UBC 
                   
               
               
                   
               
               
                 117 
                 IPHQRSSL 
                 PRCA 
                 AML 
                   
               
               
                   
               
               
                 118 
                 NPERHKPSF 
                   
                 AML, OC, 
                   
               
               
                   
                   
                   
                 RCC, UEC 
                   
               
               
                   
               
               
                 119 
                 KATEYVHSL 
                 GBM, MEL, OC, SCLC, 
                 AML, UEC 
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 120 
                 TVRPKNAAL 
                 GBM, MEL, OC, SCLC, 
                 AML, UEC 
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 121 
                 GPFQRAAL 
                   
                 UEC 
                   
               
               
                   
               
               
                 122 
                 KPRTPFTTAQLL 
                   
                 UEC 
                   
               
               
                   
               
               
                 123 
                 RPRLRDLPAL 
                 GBC, NHL, OSCAR 
                 CCC 
                   
               
               
                   
               
               
                 124 
                 KTIDGHINL 
                 AML, BRCA, CCC, 
                 CLL, NHL, 
                   
               
               
                   
                   
                 CRC, GBC, GBM, GC, 
                 SCLC 
                   
               
               
                   
                   
                 HCC, HNSCC, MEL, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, UBC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 125 
                 SPAKQFNIY 
                 AML, BRCA, CCC, 
                 CLL, SCLC 
                   
               
               
                   
                   
                 CRC, GBC, GBM, GC, 
                   
                   
               
               
                   
                   
                 HCC, HNSCC, MEL, 
                   
                   
               
               
                   
                   
                 NHL, NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, UBC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 126 
                 MPREDAHF 
                   
                 MEL 
                   
               
               
                   
               
               
                 127 
                 KSKQVITLL 
                   
                 MEL 
                   
               
               
                   
               
               
                 128 
                 SPPATLFLFLL 
                 CCC 
                 MEL 
                   
               
               
                   
               
               
                 129 
                 MTLPATTLTL 
                   
                 NHL 
                   
               
               
                   
               
               
                 130 
                 GAYDKARYL 
                 HCC, PRCA 
                 BRCA 
                   
               
               
                   
               
               
                 131 
                 MPFRNIRSIL 
                 BRCA, OC, SCLC 
                 CCC, HCC 
                   
               
               
                   
               
               
                 132 
                 LPRLPVGSLV 
                 BRCA, CRC, GBC, 
                 HNSCC, 
                   
               
               
                   
                   
                 GC, MEL, NHL, 
                 NSCLCadeno, 
                   
               
               
                   
                   
                 NSCLCother, 
                 OSCAR, PACA 
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 133 
                 LPELPTTLTF 
                 BRCA, CRC, GBC, 
                 NSCLCadeno, 
                   
               
               
                   
                   
                 GC, HNSCC, MEL, 
                 OSCAR, PACA 
                   
               
               
                   
                   
                 NHL, NSCLCsquam, 
                   
                   
               
               
                   
                   
                 OC, UEC 
                   
                   
               
               
                   
               
               
                 134 
                 VAAAARLTL 
                   
                 MEL 
                   
               
               
                   
               
               
                 135 
                 MPRLLRLSL 
                 GBC, HCC, NHL, OC, 
                 BRCA 
                   
               
               
                   
                   
                 SCLC, UEC 
                   
                   
               
               
                   
               
               
                 136 
                 QPDHAGIFRVF 
                 NSCLCother, OSCAR 
                 HNSCC 
                   
               
               
                   
               
               
                 137 
                 SPQLSYFEY 
                 GC, NSCLCadeno, 
                 CCC, HNSCC, 
                   
               
               
                   
                   
                 NSCLCother, PACA, 
                 NSCLCsquam, 
                   
               
               
                   
                   
                 UBC 
                 OSCAR 
                   
               
               
                   
               
               
                 138 
                 VPFNLITEY 
                 HCC 
                 MEL 
                   
               
               
                   
               
               
                 139 
                 LVILQHQAM 
                 PACA, UEC 
                 GC 
                   
               
               
                   
               
               
                 140 
                 TPFPDIHWF 
                 NSCLCadeno 
                 MEL 
                   
               
               
                   
               
               
                 141 
                 YGPYGSGSGW 
                 NHL 
                 HNSCC, MEL 
                   
               
               
                   
               
               
                 142 
                 HPFKMKWQY 
                 OSCAR 
                 RCC 
                   
               
               
                   
               
               
                 143 
                 YPMIPPAQL 
                 SCLC 
                 GBM 
                   
               
               
                   
               
               
                 144 
                 RPVQGIPTY 
                   
                 MEL 
                   
               
               
                   
               
               
                 145 
                 VPAQRLGLLL 
                 NSCLCother 
                 CLL 
                   
               
               
                   
               
               
                 146 
                 SPTRGSEF 
                   
                 GBM 
                   
               
               
                   
               
               
                 147 
                 HVAQPAVVL 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 148 
                 KPHLIYRQ 
                 BRCA, OC, UEC 
                 SCLC 
                   
               
               
                   
               
               
                 149 
                 SPSSVFTSK 
                   
                 BRCA 
                   
               
               
                   
               
               
                 150 
                 APLHGGGSL 
                   
                 PRCA 
                   
               
               
                   
               
               
                 151 
                 QPTWNTQTRL 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 152 
                 SSASFSSELFRH 
                   
                 GBM 
                   
               
               
                   
               
               
                 153 
                 QPVHSLCSA 
                   
                 GC, PACA 
                   
               
               
                   
               
               
                 154 
                 RPPPSRRAVL 
                   
                 GBM 
                   
               
               
                   
               
               
                 155 
                 APIPRLIEG 
                 HCC, OSCAR 
                 HNSCC 
                   
               
               
                   
               
               
                 156 
                 GSRPVTGSV 
                 BRCA, GBC, MEL, OC 
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 UBC 
                   
               
               
                   
               
               
                 157 
                 RPVTGSVC 
                 BRCA, GBC, MEL, OC 
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 UBC 
                   
               
               
                   
               
               
                 158 
                 SVPVATVEL 
                   
                 NHL 
                   
               
               
                   
               
               
                 159 
                 TPMTVPRI 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 160 
                 IPVSHPVLTF 
                   
                 CLL, NHL 
                   
               
               
                   
               
               
                 161 
                 ASKILETSL 
                   
                 MEL 
                   
               
               
                   
               
               
                 162 
                 IPIRVDQNGAF 
                 AML, GBM 
                 CLL 
                   
               
               
                   
               
               
                 163 
                 FRYPNGVSL 
                   
                 HCC 
                   
               
               
                   
               
               
                 164 
                 RAAGRRLQL 
                   
                 HCC 
                   
               
               
                   
               
               
                 165 
                 RPSKEMQVTI 
                 CCC, GC 
                 PACA 
                   
               
               
                   
               
               
                 166 
                 YAYTSRVIL 
                 AML 
                 CLL, NHL 
                   
               
               
                   
               
               
                 167 
                 NVNPARKGL 
                 OC, OSCAR 
                 AML 
                   
               
               
                   
               
               
                 168 
                 SPSGQRDVSL 
                   
                 MEL 
                   
               
               
                   
               
               
                 169 
                 RPFSVSSISQL 
                   
                 MEL 
                   
               
               
                   
               
               
                 170 
                 APEGKRLGF 
                   
                 MEL 
                   
               
               
                   
               
               
                 171 
                 LPLGGHKSL 
                   
                 MEL 
                   
               
               
                   
               
               
                 172 
                 SAQSLHPVL 
                   
                 GBM 
                   
               
               
                   
               
               
                 173 
                 VIINNPISL 
                   
                 MEL 
                   
               
               
                   
               
               
                 174 
                 IPVTSSVTL 
                   
                 MEL 
                   
               
               
                   
               
               
                 175 
                 AAFPHKIIF 
                   
                 RCC 
                   
               
               
                   
               
               
                 176 
                 QPLDICHSF 
                 CCC, GBC, GC, HCC, 
                 CRC, MEL 
                   
               
               
                   
                   
                 HNSCC, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, UBC 
                   
                   
               
               
                   
               
               
                 177 
                 VWEPQGSSRSL 
                   
                 UEC 
                   
               
               
                   
               
               
                 178 
                 VPYYPRANL 
                 CRC, GC, HNSCC, 
                 GBC 
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, UBC 
                   
                   
               
               
                   
               
               
                 179 
                 PRVRLLLL 
                 AML 
                 SCLC 
                   
               
               
                   
               
               
                 180 
                 RLRDYISSL 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 181 
                 LPVSPARAL 
                 CCC, CRC, GBC, 
                 BRCA, 
                   
               
               
                   
                   
                 GBM, GC, MEL, NHL, 
                 HNSCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 OSCAR 
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 PACA, UBC, UEC 
                   
                   
               
               
                   
               
               
                 182 
                 RPLPVSPARAL 
                 CCC, CRC, GBC, 
                 BRCA, 
                   
               
               
                   
                   
                 GBM, GC, MEL, NHL, 
                 HNSCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 OSCAR 
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 PACA, UBC, UEC 
                   
                   
               
               
                   
               
               
                 183 
                 VPRRPARAL 
                   
                 GBM 
                   
               
               
                   
               
               
                 184 
                 KIIASGNHL 
                 BRCA, CLL, NHL, RCC 
                 UBC 
                   
               
               
                   
               
               
                 185 
                 RPVLTASSF 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 186 
                 VPLPAGGGTVLT 
                   
                 SCLC 
                   
               
               
                   
               
               
                 187 
                 APPPPPPPF 
                 AML, CLL, NHL 
                 PRCA 
                   
               
               
                   
               
               
                 188 
                 HAAASFETL 
                 MEL 
                 CLL, NHL 
                   
               
               
                   
               
               
                 189 
                 QPQCSTHIL 
                   
                 HCC 
                   
               
               
                   
               
               
                 190 
                 RLAHVRARL 
                 BRCA, HCC, OC 
                 PRCA 
                   
               
               
                   
               
               
                 191 
                 KPKAVKPKAA 
                 CLL 
                 NHL 
                   
               
               
                   
               
               
                 192 
                 IPFADVKSF 
                 NSCLCsquam 
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 NSCLCother 
                   
               
               
                   
               
               
                 193 
                 LPALKEEAF 
                   
                 PRCA 
                   
               
               
                   
               
               
                 194 
                 HPNKIKASL 
                   
                 BRCA 
                   
               
               
                   
               
               
                 195 
                 NPIFGRKEL 
                   
                 UEC 
                   
               
               
                   
               
               
                 196 
                 RPSGTAGAAL 
                   
                 GBM 
                   
               
               
                   
               
               
                 197 
                 RPSGTAGAALLA 
                   
                 GBM 
                   
               
               
                   
               
               
                 198 
                 LPSPAHAFRAL 
                 HCC, MEL, NHL, OC, 
                 UBC 
                   
               
               
                   
                   
                 PACA, UEC 
                   
                   
               
               
                   
               
               
                 199 
                 SPFWIHQA 
                   
                 AML 
                   
               
               
                   
               
               
                 200 
                 EPFHLIVSY 
                 MEL 
                 CLL, NHL 
                   
               
               
                   
               
               
                 201 
                 LPIARVLTV 
                   
                 BRCA 
                   
               
               
                   
               
               
                 202 
                 SPSREASAL 
                   
                 AML 
                   
               
               
                   
               
               
                 203 
                 KPRGPIDI 
                 MEL 
                 PRCA 
                   
               
               
                   
               
               
                 204 
                 FPYSGDKILV 
                   
                 GBM 
                   
               
               
                   
               
               
                 205 
                 LPPALLTTV 
                   
                 GBM 
                   
               
               
                   
               
               
                 206 
                 TPRIGPKVSL 
                   
                 GBM 
                   
               
               
                   
               
               
                 207 
                 VPSDITTAF 
                   
                 GBM 
                   
               
               
                   
               
               
                 208 
                 RNRQVATAL 
                 AML 
                 CCC 
                   
               
               
                   
               
               
                 209 
                 KIEQIRAVL 
                 CCC, GBC, GC, 
                 OSCAR 
                   
               
               
                   
                   
                 HNSCC, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, PACA, 
                   
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 210 
                 IPENRVVSY 
                   
                 CRC 
                   
               
               
                   
               
               
                 211 
                 IPDTIASVL 
                   
                 MEL 
                   
               
               
                   
               
               
                 212 
                 VPYAAQAAL 
                 CRC, GBC, SCLC, 
                 HCC 
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 213 
                 RPYQDAPVA 
                 NHL, RCC 
                 GBM 
                   
               
               
                   
               
               
                 214 
                 LPLKFFPII 
                 CCC, GBC, GC, HCC, 
                 OC 
                   
               
               
                   
                   
                 NSCLCadeno, PACA, 
                   
                   
               
               
                   
                   
                 SCLC 
                   
                   
               
               
                   
               
               
                 215 
                 IPVAIKEL 
                   
                 GBM 
                   
               
               
                   
               
               
                 216 
                 LPWEQNEQV 
                   
                 HCC 
                   
               
               
                   
               
               
                 217 
                 SPGDKRLAAYL 
                   
                 HCC 
                   
               
               
                   
               
               
                 218 
                 VQRTPPPI 
                 CCC, CRC, GBC, GC, 
                 RCC, SCLC 
                   
               
               
                   
                   
                 PACA 
                   
                   
               
               
                   
               
               
                 219 
                 VPHTGRYTCL 
                   
                 MEL 
                   
               
               
                   
               
               
                 220 
                 RPAPGPAPFV 
                 GBC, HNSCC, MEL, 
                 CRC, GC 
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, UBC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 221 
                 LPQRPNARL 
                 CCC, GBC, GC, 
                 HNSCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 OSCAR 
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, PACA, 
                   
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 222 
                 MLKTTLTAF 
                   
                 HCC 
                   
               
               
                   
               
               
                 223 
                 KAHVRIEL 
                 HCC 
                 CRC 
                   
               
               
                   
               
               
                 224 
                 SPIIHSILL 
                 BRCA, HNSCC, 
                 SCLC 
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 225 
                 SPIIHSIL 
                 BRCA, HNSCC, 
                 SCLC 
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 226 
                 APGGSSRSSL 
                   
                 AML 
                   
               
               
                   
               
               
                 227 
                 RPGTGQGGL 
                   
                 AML 
                   
               
               
                   
               
               
                 228 
                 RPTAASQSRAL 
                   
                 AML 
                   
               
               
                   
               
               
                 229 
                 FPNAGPRHLL 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 230 
                 DVIDDIISL 
                   
                 MEL 
                   
               
               
                   
               
               
                 231 
                 SPITLQAL 
                   
                 HCC 
                   
               
               
                   
               
               
                 232 
                 TAYPSLRLL 
                 HNSCC, MEL, 
                 SCLC 
                   
               
               
                   
                   
                 NSCLCsquam 
                   
                   
               
               
                   
               
               
                 233 
                 MAYDRFIAI 
                 BRCA, GBC, HCC, 
                 NHL 
                   
               
               
                   
                   
                 HNSCC, MEL, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, PACA, 
                   
                   
               
               
                   
                   
                 SCLC 
                   
                   
               
               
                   
               
               
                 234 
                 HPRAPGEQQRL 
                 HCC 
                 CRC 
                   
               
               
                   
               
               
                 235 
                 AQNPAGTAL 
                   
                 MEL 
                   
               
               
                   
               
               
                 236 
                 TPELKSSIL 
                   
                 HCC 
                   
               
               
                   
               
               
                 237 
                 LPRAGGAF 
                 CCC, GC, HNSCC, 
                 OSCAR 
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, PACA, 
                   
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 238 
                 LPRAGGAFLM 
                 CCC, GC, HNSCC, 
                 OSCAR 
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, PACA, 
                   
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 239 
                 VLPRAGGAFLM 
                 CCC, GC, HNSCC, 
                 OSCAR 
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, PACA, 
                   
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 240 
                 RVMLPKAAL 
                 BRCA, CCC, NHL, 
                 GBC 
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, SCLC, UBC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 241 
                 LPKAALLV 
                 BRCA, CCC, NHL, 
                 GBC 
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, SCLC, UBC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 242 
                 IPETASVVAI 
                 MEL 
                 CLL, NHL 
                   
               
               
                   
               
               
                 243 
                 MARTGGMVVI 
                   
                 UBC 
                   
               
               
                   
               
               
                 244 
                 VPAHLVAA 
                   
                 RCC 
                   
               
               
                   
               
               
                 245 
                 GPVPSPLAL 
                   
                 CLL 
                   
               
               
                   
               
               
                 246 
                 RPILKEQSSSSF 
                   
                 HNSCC 
                   
               
               
                   
               
               
                 247 
                 SPVGVGQRL 
                 GBM 
                 SCLC 
                   
               
               
                   
               
               
                 248 
                 KPYDGIPAS 
                   
                 GBM 
                   
               
               
                   
               
               
                 249 
                 SPRSGVLL 
                 OC 
                 UEC 
                   
               
               
                   
               
               
                 250 
                 APAAPAAVPS 
                 CRC, GBM, GC, 
                 NSCLCadeno, 
                   
               
               
                   
                   
                 HNSCC, SCLC 
                 NSCLCsquam 
                   
               
               
                   
               
               
                 251 
                 MPVDSFNSM 
                 CCC, GBC, 
                 CRC 
                   
               
               
                   
                   
                 NSCLCadeno, UEC 
                   
                   
               
               
                   
               
               
                 252 
                 QPENSLEGISL 
                 CCC, GBC, 
                 CRC 
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCother, PACA, 
                   
                   
               
               
                   
                   
                 RCC, UEC 
                   
                   
               
               
                   
               
               
                 253 
                 MPVDSFNSML 
                 CCC, GBC, 
                 CRC 
                   
               
               
                   
                   
                 NSCLCadeno, UEC 
                   
                   
               
               
                   
               
               
                 254 
                 RVIQGTTTL 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 255 
                 VPSHWMVAL 
                 CLL 
                 NHL 
                   
               
               
                   
               
               
                 256 
                 SPVPSHWMVAL 
                 CLL 
                 NHL 
                   
               
               
                   
               
               
                 257 
                 APYGTLRKS 
                   
                 CCC 
                   
               
               
                   
               
               
                 258 
                 SVIGPNSRL 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 259 
                 VPMPGVQAV 
                 CRC 
                 UEC 
                   
               
               
                   
               
               
                 260 
                 LVQSSRSEV 
                 OSCAR 
                 HNSCC 
                   
               
               
                   
               
               
                 261 
                 SPSTSRTPL 
                   
                 GBM 
                   
               
               
                   
               
               
                 262 
                 SPSTSRTPLLSSL 
                   
                 GBM 
                   
               
               
                   
               
               
                 263 
                 SQRPPATSQA 
                 OC 
                 NHL 
                   
               
               
                   
               
               
                 264 
                 APRPGNWIL 
                 MEL, NSCLCsquam, 
                 UEC 
                   
               
               
                   
                   
                 OC, RCC, SCLC 
                   
                   
               
               
                   
               
               
                 265 
                 FPRKPYEGRV 
                   
                 MEL 
                   
               
               
                   
               
               
                 266 
                 KPYEGRVEI 
                   
                 MEL 
                   
               
               
                   
               
               
                 267 
                 MPVPGILL 
                   
                 MEL 
                   
               
               
                   
               
               
                 268 
                 EPLSVTASY 
                 GBC, SCLC 
                 HCC 
                   
               
               
                   
               
               
                 269 
                 FTVSSSSAM 
                   
                 PACA 
                   
               
               
                   
               
               
                 270 
                 SPRGTTSTL 
                   
                 PACA 
                   
               
               
                   
               
               
                 271 
                 SPTPVFTTL 
                   
                 PACA 
                   
               
               
                   
               
               
                 272 
                 SSPRGTTSTL 
                   
                 PACA 
                   
               
               
                   
               
               
                 273 
                 TDTPSTTPTTI 
                   
                 PACA 
                   
               
               
                   
               
               
                 274 
                 KPIRTGISPLAL 
                   
                 HCC 
                   
               
               
                   
               
               
                 275 
                 IPAPQGAVL 
                   
                 NSCLCother 
                   
               
               
                   
               
               
                 276 
                 RPVWDVRSA 
                 NSCLCadeno 
                 HNSCC 
                   
               
               
                   
               
               
                 277 
                 MPPLLIVAF 
                 UBC 
                 BRCA 
                   
               
               
                   
               
               
                 278 
                 LIAARGSLVL 
                 GBM, HCC, MEL, OC 
                 SCLC 
                   
               
               
                   
               
               
                 279 
                 APADEPRTVL 
                 BRCA, CCC, CRC, 
                 GBM 
                   
               
               
                   
                   
                 GBC, GC, HNSCC, 
                   
                   
               
               
                   
                   
                 NHL, NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, PRCA, 
                   
                   
               
               
                   
                   
                 SCLC, UBC, UEC 
                   
                   
               
               
                   
               
               
                 280 
                 LPRAFLQSL 
                 BRCA, CCC, CRC, 
                 GBM 
                   
               
               
                   
                   
                 GBC, GC, HNSCC, 
                   
                   
               
               
                   
                   
                 NHL, NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, PRCA, 
                   
                   
               
               
                   
                   
                 SCLC, UBC, UEC 
                   
                   
               
               
                   
               
               
                 281 
                 NPRSPPATM 
                 HCC, UEC 
                 UBC 
                   
               
               
                   
               
               
                 282 
                 AVRLPTPNL 
                 AML 
                   
                   
               
               
                   
               
               
                 283 
                 RPQPGWRESL 
                 GBC, SCLC 
                   
                   
               
               
                   
               
               
                 284 
                 RPSAPRGPP 
                 CRC 
                   
                   
               
               
                   
               
               
                 285 
                 RITWKGLLL 
                 CCC 
                   
                   
               
               
                   
               
               
                 286 
                 APARPAAAF 
                 MEL, OC 
                   
                   
               
               
                   
               
               
                 287 
                 SPIPRPLFL 
                 BRCA, SCLC 
                   
                   
               
               
                   
               
               
                 288 
                 LHAMNSLSAM 
                 CCC, OC, SCLC, UBC, 
                   
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 289 
                 LPYEKVSRL 
                 CCC 
                   
                   
               
               
                   
               
               
                 290 
                 RPTHPLRSF 
                 GBM 
                   
                   
               
               
                   
               
               
                 291 
                 SPSKSLEM 
                 CLL, CRC 
                   
                   
               
               
                   
               
               
                 292 
                 LPMTHRLQL 
                 CCC 
                   
                   
               
               
                   
               
               
                 293 
                 FPYDKPLIM 
                 CCC, GBC, 
                   
                   
               
               
                   
                   
                 NSCLCadeno 
                   
                   
               
               
                   
               
               
                 294 
                 VPKPAIPSSSVL 
                 GBM, NSCLCsquam, 
                   
                   
               
               
                   
                   
                 SCLC 
                   
                   
               
               
                   
               
               
                 295 
                 HPRWIEPTVM 
                 PRCA 
                   
                   
               
               
                   
               
               
                 296 
                 SPLLMQRTL 
                 AML, CLL 
                   
                   
               
               
                   
               
               
                 297 
                 FPIKYVNDF 
                 CCC, GBC, 
                   
                   
               
               
                   
                   
                 NSCLCadeno 
                   
                   
               
               
                   
               
               
                 298 
                 RVLLRWISL 
                 GBM 
                   
                   
               
               
                   
               
               
                 299 
                 SPFSGGPVSF 
                 RCC 
                   
                   
               
               
                   
               
               
                 300 
                 HPYSDLADVF 
                 SCLC 
                   
                   
               
               
                   
               
               
                 301 
                 FPAFLEAM 
                 SCLC 
                   
                   
               
               
                   
               
               
                 302 
                 IPIDQILNSF 
                 SCLC 
                   
                   
               
               
                   
               
               
                 303 
                 RPPPPCIAL 
                 SCLC 
                   
                   
               
               
                   
               
               
                 304 
                 SPLIGDFPAF 
                 SCLC 
                   
                   
               
               
                   
               
               
                 305 
                 AASPVGSAL 
                 HCC 
                   
                   
               
               
                   
               
               
                 306 
                 RPFPLALL 
                 CRC 
                   
                   
               
               
                   
               
               
                 307 
                 RPHQKGWLSI 
                 HCC 
                   
                   
               
               
                   
               
               
                 308 
                 RPDVVRTLL 
                 CCC, HNSCC, OSCAR 
                   
                   
               
               
                   
               
               
                 309 
                 FAFYGGKSL 
                 GBM, HCC, HNSCC, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, 
                   
                   
               
               
                   
                   
                 OSCAR, SCLC, UBC 
                   
                   
               
               
                   
               
               
                 310 
                 SPGWAQTQL 
                 CRC, GC, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, PACA, 
                   
                   
               
               
                   
                   
                 RCC 
                   
                   
               
               
                   
               
               
                 311 
                 APRLALDPDAL 
                 GBM, SCLC, UEC 
                   
                   
               
               
                   
               
               
                 312 
                 SPSLQSSRESL 
                 BRCA, CCC, CRC, 
                   
                   
               
               
                   
                   
                 GBC, GBM, GC, 
                   
                   
               
               
                   
                   
                 HNSCC, MEL, NHL, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, SCLC, 
                   
                   
               
               
                   
                   
                 UBC, UEC 
                   
                   
               
               
                   
               
               
                 313 
                 VPLSSYVSI 
                 GBM 
                   
                   
               
               
                   
               
               
                 314 
                 IALMKLAGPL 
                 CCC, GBC, GC, HCC, 
                   
                   
               
               
                   
                   
                 OC, PACA, SCLC 
                   
                   
               
               
                   
               
               
                 315 
                 APVVFPAL 
                 SCLC 
                   
                   
               
               
                   
               
               
                 316 
                 NPREPEKSL 
                 CRC, GBC, GC, PACA 
                   
                   
               
               
                   
               
               
                 317 
                 MPYNSAHHCVV 
                 CLL, OC 
                   
                   
               
               
                   
               
               
                 318 
                 TPISNTGVL 
                 CLL, NHL 
                   
                   
               
               
                   
               
               
                 319 
                 RPLDTFRVL 
                 PRCA, UBC 
                   
                   
               
               
                   
               
               
                 320 
                 APMHIDRNIL 
                 HCC 
                   
                   
               
               
                   
               
               
                 321 
                 QPQQPGFFL 
                 AML 
                   
                   
               
               
                   
               
               
                 322 
                 RAVPVGSGL 
                 SCLC 
                   
                   
               
               
                   
               
               
                 323 
                 TPHGITDIL 
                 GC 
                   
                   
               
               
                   
               
               
                 324 
                 LPAPLRISL 
                 GBM 
                   
                   
               
               
                   
               
               
                 325 
                 SPRSNPVRL 
                 NHL 
                   
                   
               
               
                   
               
               
                 326 
                 IPPFTQRVF 
                 HNSCC, NSCLCsquam 
                   
                   
               
               
                   
               
               
                 327 
                 GPRTTQSSVL 
                 CLL, NHL 
                   
                   
               
               
                   
               
               
                 328 
                 LPLHRGDLVI 
                 CLL 
                   
                   
               
               
                   
               
               
                 329 
                 QPANFIVLL 
                 GBC, GC, PACA 
                   
                   
               
               
                   
               
               
                 330 
                 RPFSAIAEL 
                 CCC 
                   
                   
               
               
                   
               
               
                 331 
                 SPDSAILKL 
                 PRCA 
                   
                   
               
               
                   
               
               
                 332 
                 SPYAGSTAF 
                 BRCA 
                   
                   
               
               
                   
               
               
                 333 
                 SVLPRALSL 
                 SCLC 
                   
                   
               
               
                   
               
               
                 334 
                 YPLSLALHF 
                 SCLC 
                   
                   
               
               
                   
               
               
                 335 
                 VPPQNPRPSL 
                 AML 
                   
                   
               
               
                   
               
               
                 336 
                 YPLQGPGLLSV 
                 NSCLCother, SCLC 
                   
                   
               
               
                   
               
               
                 337 
                 IPTSRVITL 
                 HCC, NHL 
                   
                   
               
               
                   
               
               
                 338 
                 MPATPSLKV 
                 CCC, CRC 
                   
                   
               
               
                   
               
               
                 339 
                 GPQRTTSV 
                 NHL 
                   
                   
               
               
                   
               
               
                 340 
                 APEPRAALL 
                 MEL 
                   
                   
               
               
                   
               
               
                 341 
                 LPRSPPLKVL 
                 GBC, NHL 
                   
                   
               
               
                   
               
               
                 342 
                 RPRPPKVL 
                 HCC, NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam 
                   
                   
               
               
                   
               
               
                 343 
                 RPRPPKVLGL 
                 HCC, NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam 
                   
                   
               
               
                   
               
               
                 344 
                 VPYPSPTCV 
                 HCC, PRCA 
                   
                   
               
               
                   
               
               
                 345 
                 SAAPPGASL 
                 HCC, PRCA 
                   
                   
               
               
                   
               
               
                 346 
                 IPMPRITWL 
                 UBC 
                   
                   
               
               
                   
               
               
                 347 
                 SPLEKINSF 
                 MEL, SCLC 
                   
                   
               
               
                   
               
               
                 348 
                 HPAPPVTSA 
                 HNSCC, OC, OSCAR, 
                   
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 349 
                 QPRDGWPMML 
                 HNSCC, OC, OSCAR, 
                   
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                 350 
                 RPKSTLMNF 
                 HNSCC, OC, OSCAR, 
                   
                   
               
               
                   
                   
                 UBC 
                   
                   
               
               
                   
               
               
                 351 
                 SPYADIIPSA 
                 BRCA, MEL 
                   
                   
               
               
                   
               
               
                 352 
                 LPAFSKIGGIL 
                 SCLC 
                   
                   
               
               
                   
               
               
                 353 
                 KPRATWTL 
                 HNSCC, OC 
                   
                   
               
               
                   
               
               
                 354 
                 APAKDARASL 
                 GBM 
                   
                   
               
               
                   
               
               
                 355 
                 APKTSFIAA 
                 CRC, GC, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, PACA 
                   
                   
               
               
                   
               
               
                 356 
                 RPFLRLPSL 
                 CRC, HNSCC, OSCAR 
                   
                   
               
               
                   
               
               
                 357 
                 LPPHIFAI 
                 MEL 
                   
                   
               
               
                   
               
               
                 358 
                 APSMLRKNQL 
                 BRCA, GBM, MEL, 
                 GBC, UBC 
                 HCC 
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 OSCAR, SCLC 
                   
                   
               
               
                   
               
               
                 359 
                 SPRRLVELAGQS 
                 AML, BRCA, GC, HCC, 
                 GBC, HNSCC, 
                 MEL, OC, 
               
               
                   
                 L 
                 NHL, OSCAR, UBC 
                 NSCLCadeno, 
                 SCLC, UEC 
               
               
                   
                   
                   
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 RCC 
                   
               
               
                   
               
               
                 360 
                 SPASRSISLL 
                 AML, GC, HNSCC, 
                 CLL, NHL 
                 RCC 
               
               
                   
                   
                 OC, OSCAR 
                   
                   
               
               
                   
               
               
                 361 
                 SPYGSDRLVQL 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 362 
                 KPMLPPAAF 
                   
                 UEC 
                   
               
               
                   
               
               
                 363 
                 KPRTPFTTA 
                   
                 UEC 
                   
               
               
                   
               
               
                 364 
                 KPRTPFTTAQL 
                   
                 UEC 
                   
               
               
                   
               
               
                 365 
                 RPKHFLQML 
                 HNSCC, NHL, 
                 OC 
                   
               
               
                   
                   
                 NSCLCsquam, OSCAR 
                   
                   
               
               
                   
               
               
                 366 
                 SPTLRQLDL 
                 HCC 
                 NHL 
                   
               
               
                   
               
               
                 367 
                 APQVHIFSL 
                 GBM, OC 
                 CCC 
                   
               
               
                   
               
               
                 368 
                 NPASRLTAL 
                 PRCA, UEC 
                 BRCA 
                   
               
               
                   
               
               
                 369 
                 RPYGCVLRAA 
                 AML, CCC, GBC, GC, 
                 CLL, NHL 
                 RCC 
               
               
                   
                   
                 HNSCC, OC, OSCAR 
                   
                   
               
               
                   
               
               
                 370 
                 AAHEFGHVL 
                 HCC, NSCLCother, 
                 BRCA, CCC, 
                   
               
               
                   
                   
                 OC, RCC, SCLC 
                 CRC, GBC, 
                   
               
               
                   
                   
                   
                 GC, HNSCC, 
                   
               
               
                   
                   
                   
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 OSCAR, 
                   
               
               
                   
                   
                   
                 PACA, UBC, 
                   
               
               
                   
                   
                   
                 UEC 
                   
               
               
                   
               
               
                 371 
                 APRSPGQVTPRG 
                 HCC, NSCLCadeno, 
                 CRC, GBC, 
                   
               
               
                   
                 L 
                 NSCLCsquam, PACA, 
                 GC, RCC 
                   
               
               
                   
                   
                 SCLC 
                   
                   
               
               
                   
               
               
                 372 
                 SPSSASLTL 
                 GBC, GC, HCC, MEL, 
                 HNSCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 NSCLCsquam, 
                   
               
               
                   
                   
                 NSCLCother, PACA, 
                 OC, OSCAR, 
                   
               
               
                   
                   
                 UEC 
                 SCLC, UBC 
                   
               
               
                   
               
               
                 373 
                 LPKPDLPQLI 
                 BRCA, HCC 
                 PRCA 
                   
               
               
                   
               
               
                 374 
                 KPRNMTGLDL 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 375 
                 LPRGVLEGL 
                 BRCA, CCC, CRC, 
                 GBM 
                   
               
               
                   
                   
                 GBC, GC, HNSCC, 
                   
                   
               
               
                   
                   
                 NHL, NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, PRCA, 
                   
                   
               
               
                   
                   
                 SCLC, UBC, UEC 
                   
                   
               
               
                   
               
               
                 376 
                 FPQVGRTAL 
                 CLL 
                   
                   
               
               
                   
               
               
                 377 
                 SPFSKRIKL 
                 AML, CLL, NHL 
                   
                   
               
               
                   
               
               
                 378 
                 SPRQPRLDF 
                 NSCLCsquam, SCLC 
                   
                   
               
               
                   
               
               
                 379 
                 GPRQVLFPL 
                 GBM 
                   
                   
               
               
                   
               
               
                 380 
                 SPYPGSAAF 
                 BRCA, GC 
                   
                   
               
               
                   
               
               
                 381 
                 APRPRLLLL 
                 CCC, GBC, MEL 
                   
                   
               
               
                   
               
               
                 382 
                 RPGPQRTTSV 
                 NHL 
                   
                   
               
               
                   
               
               
                 383 
                 KPRATWTLKL 
                 HNSCC, OC 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9b 
               
             
            
               
                   
               
               
                 Expression scores. The table lists peptides from genes that are very highly 
               
               
                 over-expressed in tumors compared to a panel of normal tissues (+++), highly over- 
               
               
                 expressed in tumors compared to a panel of normal tissues (++) or over-expressed in 
               
               
                 tumors compared to a panel of normal tissues (+). The baseline for this score was 
               
               
                 calculated from measurements of the following relevant normal tissues: adipose tissue, 
               
               
                 adrenal gland, bile duct, blood cells, blood vessels, bone marrow, brain, esophagus, eye, 
               
               
                 gallbladder, heart, head &amp; neck, kidney, large intestine, liver, lung, lymph node, nerve, 
               
               
                 parathyroid, pancreas, pituitary, pleura, skeletal muscle, skin, small intestine, spleen, 
               
               
                 stomach, thyroid gland, trachea, ureter, urinary bladder. In case expression data for 
               
               
                 several samples of the same tissue type were available, the arithmetic mean of all 
               
               
                 respective samples was used for the calculation. AML: acute myeloid leukemia; BRCA: 
               
               
                 breast cancer; CCC: cholangiocellular carcinoma; CLL: chronic lymphocytic leukemia; 
               
               
                 CRC: colorectal cancer; GBC: gallbladder cancer; GBM: glioblastoma; GC: gastric 
               
               
                 cancer; HCC: hepatocellular carcinoma; HNSCC: head and neck squamous cell 
               
               
                 carcinoma; MEL: melanoma; NHL: non-Hodgkin lymphoma; NSCLCadeno: non-small cell 
               
               
                 lung cancer adenocarcinoma; NSCLCother: NSCLC samples that could not 
               
               
                 unambiguously be assigned to NSCLCadeno or NSCLCsquam; NSCLCsquam: 
               
               
                 squamous cell non-small cell lung cancer; OC: ovarian cancer; OSCAR: esophageal 
               
               
                 cancer; PACA: pancreatic cancer; PRCA: prostate cancer; RCC: renal cell carcinoma; 
               
               
                 SCLC: small cell lung cancer; UBC: urinary bladder carcinoma; UEC: uterine and 
               
               
                 endometrial cancer 
               
            
           
           
               
               
               
            
               
                   
                   
                 Gene Expression in tumor samples 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                   
                 very highly 
               
               
                 Seq 
                   
                   
                   
                 over- 
               
               
                 ID 
                   
                   
                 highly over- 
                 expressed 
               
               
                 No 
                 Sequence 
                 over-expressed (+) 
                 expressed (++) 
                 (+++) 
               
               
                   
               
               
                 448 
                 TVYGEPRKL 
                 BRCA, CRC, GC, 
                 HCC, 
                 GBC, 
               
               
                   
                   
                 UEC 
                 NSCLCadeno 
                 HNSCC, 
               
               
                   
                   
                   
                   
                 MEL, 
               
               
                   
                   
                   
                   
                 NSCLCsquam, 
               
               
                   
                   
                   
                   
                 OC, 
               
               
                   
                   
                   
                   
                 OSCAR, 
               
               
                   
                   
                   
                   
                 SCLC, UBC 
               
               
                   
               
               
                 449 
                 RPKTSVNLISSL 
                 HCC, NHL, RCC 
                 CCC, GBC, 
                 CRC, 
               
               
                   
                   
                   
                 GC, MEL, 
                 HNSCC, 
               
               
                   
                   
                   
                 NSCLCadeno, 
                 NSCLCother, 
               
               
                   
                   
                   
                 OC, OSCAR, 
                 NSCLCsquam, 
               
               
                   
                   
                   
                 PACA, UBC, 
                 SCLC 
               
               
                   
                   
                   
                 UEC 
                   
               
               
                   
               
               
                 450 
                 SAAARALLP 
                 HCC, MEL, RCC, 
                 BRCA, CRC, 
                 CCC, PACA 
               
               
                   
                   
                 SCLC 
                 GBC, GC, 
                   
               
               
                   
                   
                   
                 HNSCC, 
                   
               
               
                   
                   
                   
                 NSCLCadeno, 
                   
               
               
                   
                   
                   
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 OC, OSCAR, 
                   
               
               
                   
                   
                   
                 UBC, UEC 
                   
               
               
                   
               
               
                 451 
                 VPILPLNHAL 
                 BRCA 
                 UEC 
                   
               
               
                   
               
               
                 452 
                 QPVKKNTL 
                 HCC, UEC 
                 RCC 
                   
               
               
                   
               
               
                 453 
                 APALPGQVTI 
                 CCC, CRC, GBC, 
                 BRCA, GBM, 
                   
               
               
                   
                   
                 HCC, MEL, 
                 OC, SCLC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 UBC, UEC 
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, 
                   
                   
               
               
                   
                   
                 PACA, PRCA 
                   
                   
               
               
                   
               
               
                 454 
                 SPDPAHLESL 
                 BRCA, GC, 
                 GBC, HCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 HNSCC, MEL, 
                   
               
               
                   
                   
                 OSCAR, PACA, UEC 
                 NSCLCsquam, 
                   
               
               
                   
                   
                   
                 OC, SCLC, 
                   
               
               
                   
                   
                   
                 UBC 
                   
               
               
                   
               
               
                 455 
                 FPVQATIDF 
                 BRCA, CRC, 
                 SCLC, UEC 
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, UBC 
                   
                   
               
               
                   
               
               
                 456 
                 VPVSHPVLTL 
                   
                 CLL, NHL 
                   
               
               
                   
               
               
                 457 
                 RPPLSQRHTF 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 458 
                 VPIPTHYFVVL 
                   
                 RCC 
                   
               
               
                   
               
               
                 459 
                 SPAPWRPWI 
                 BRCA, 
                 SCLC 
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PRCA, 
                   
                   
               
               
                   
                   
                 UBC, UEC 
                   
                   
               
               
                   
               
               
                 460 
                 APLMPLGKTL 
                 GBC, GC, 
                 CCC, HNSCC, 
                   
               
               
                   
                   
                 NSCLCadeno, 
                 NSCLCsquam, 
                   
               
               
                   
                   
                 NSCLCother, PACA, 
                 OSCAR, UBC 
                   
               
               
                   
                   
                 UEC 
                   
                   
               
               
                   
               
               
                 461 
                 MPHLGPGILL 
                   
                 MEL 
                   
               
               
                   
               
               
                 462 
                 MPLLADVRL 
                   
                 MEL 
                   
               
               
                   
               
               
                 463 
                 LPTDLFNSVM 
                   
                 MEL 
                   
               
               
                   
               
               
                 464 
                 VPFVPRTSV 
                 BRCA, GC, HNSCC, 
                 CCC, CRC, 
                   
               
               
                   
                   
                 MEL, NHL, 
                 GBC 
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR, PACA, 
                   
                   
               
               
                   
                   
                 RCC, UBC, UEC 
                   
                   
               
               
                   
               
               
                 465 
                 VPKSLPYVL 
                 HNSCC, 
                 AML, HCC, 
                   
               
               
                   
                   
                 NSCLCsquam, 
                 NHL 
                   
               
               
                   
                   
                 OSCAR 
                   
                   
               
               
                   
               
               
                 466 
                 SPMEAILVSRL 
                 CRC, NSCLCadeno, 
                 RCC 
                   
               
               
                   
                   
                 NSCLCsquam, SCLC 
                   
                   
               
               
                   
               
               
                 467 
                 VPRNQDWLGVSRQ 
                   
                 MEL 
                   
               
               
                   
                 L 
                   
                   
                   
               
               
                   
               
               
                 468 
                 LPSLHVLVL 
                   
                 MEL 
                   
               
               
                   
               
               
                 469 
                 LPLDTRTSI 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 470 
                 RPNGEVKSEL 
                 RCC, SCLC 
                 CRC 
                   
               
               
                   
               
               
                 471 
                 LPLLAGTLLL 
                   
                 UEC 
                   
               
               
                   
               
               
                 472 
                 LPMPAITWY 
                   
                 MEL 
                   
               
               
                   
               
               
                 473 
                 LPGEREAAL 
                   
                 MEL 
                   
               
               
                   
               
               
                 474 
                 VPKADLLTL 
                   
                 MEL 
                   
               
               
                   
               
               
                 475 
                 IPLEIQKL 
                   
                 HCC 
                   
               
               
                   
               
               
                 476 
                 EPNPVEEIF 
                 CCC, CRC, GBM, 
                 BRCA, GBC, 
                   
               
               
                   
                   
                 GC, HNSCC, 
                 MEL, 
                   
               
               
                   
                   
                 NSCLCother, 
                 NSCLCadeno, 
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                 PACA 
                   
               
               
                   
                   
                 OSCAR 
                   
                   
               
               
                   
               
               
                 477 
                 NPVPVITWYKDNRL 
                   
                 MEL 
                   
               
               
                   
               
               
                 478 
                 APKFISPASQL 
                 RCC, SCLC 
                 CRC 
                   
               
               
                   
               
               
                 479 
                 APHAGGALL 
                 GBC, HNSCC, MEL, 
                 NHL 
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 SCLC, UEC 
                   
                   
               
               
                   
               
               
                 480 
                 VPAAPTKAL 
                 UBC 
                 GBM 
                   
               
               
                   
               
               
                 481 
                 SPARALLLALA 
                 CCC, CRC, GBC, 
                 BRCA, HNSCC, 
                   
               
               
                   
                   
                 GBM, GC, MEL, 
                 OSCAR 
                   
               
               
                   
                   
                 NHL, NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 PACA, UBC, UEC 
                   
                   
               
               
                   
               
               
                 482 
                 QPSLKKIIL 
                 CCC, CLL, GBC, GC, 
                 NSCLCadeno, 
                   
               
               
                   
                   
                 HCC, NSCLCsquam, 
                 UEC 
                   
               
               
                   
                   
                 PACA 
                   
                   
               
               
                   
               
               
                 483 
                 KPAAAGVKKVA 
                 CLL 
                 NHL 
                   
               
               
                   
               
               
                 484 
                 LPASAEPKGTM 
                 CCC, CRC, GBC, 
                 OSCAR, UBC 
                   
               
               
                   
                   
                 GC, HCC, HNSCC, 
                   
                   
               
               
                   
                   
                 NSCLCadeno, 
                   
                   
               
               
                   
                   
                 NSCLCother, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 PACA 
                   
                   
               
               
                   
               
               
                 485 
                 LPLKTKVFA 
                 CCC, NSCLCadeno, 
                 BRCA 
                   
               
               
                   
                   
                 NSCLCother, PACA, 
                   
                   
               
               
                   
                   
                 RCC 
                   
                   
               
               
                   
               
               
                 486 
                 TPTRPLPSA 
                 CCC, CRC, GBC, 
                 RCC, SCLC 
                   
               
               
                   
                   
                 GC, PACA 
                   
                   
               
               
                   
               
               
                 487 
                 IPWFIKTAF 
                   
                 MEL 
                   
               
               
                   
               
               
                 488 
                 LPLGGLPLLI 
                 NHL 
                 CLL 
                   
               
               
                   
               
               
                 489 
                 WPNHIMLVL 
                 BRCA, MEL, OC 
                 PRCA 
                   
               
               
                   
               
               
                 490 
                 APRGPAQGEAA 
                   
                 AML 
                   
               
               
                   
               
               
                 491 
                 MPEADLKRIF 
                   
                 MEL 
                   
               
               
                   
               
               
                 492 
                 IPFSVDEI 
                 CCC, GBC, 
                 CRC 
                   
               
               
                   
                   
                 NSCLCadeno, UEC 
                   
                   
               
               
                   
               
               
                 493 
                 LPLQQYKLV 
                 CRC, GBM, GC, 
                 NSCLCadeno 
                   
               
               
                   
                   
                 HNSCC, 
                   
                   
               
               
                   
                   
                 NSCLCsquam, SCLC 
                   
                   
               
               
                   
               
               
                 494 
                 LPLRAVNLNL 
                 GBC, GBM, MEL, 
                 SCLC 
                   
               
               
                   
                   
                 NSCLCsquam, OC, 
                   
                   
               
               
                   
                   
                 OSCAR 
                   
                   
               
               
                   
               
               
                 495 
                 SPSYTQASL 
                   
                 BRCA 
                   
               
               
                   
               
               
                 496 
                 MPAVSGPGPLF 
                   
                 PRCA 
                   
               
               
                   
               
               
                 497 
                 YVVKPLHPF 
                 NSCLCother, 
                 NSCLCadeno 
                   
               
               
                   
                   
                 NSCLCsquam 
                   
                   
               
               
                   
               
               
                 498 
                 RPQPQPRPAL 
                 CLL, NHL, OC, 
                 CCC, GBC, 
                   
               
               
                   
                   
                 OSCAR, UBC 
                 HNSCC 
                   
               
               
                   
               
               
                 499 
                 QPVLPSPAC 
                   
                 MEL 
               
               
                   
               
            
           
         
       
     
     Example 3 
     In Vitro Immunogenicity for MHC Class I Presented Peptides 
     In order to obtain information regarding the immunogenicity of the TUMAPs of the present invention, the inventors performed investigations using an in vitro T-cell priming assay based on repeated stimulations of CD8+ T cells with artificial antigen presenting cells (aAPCs) loaded with peptide/MHC complexes and anti-CD28 antibody. This way the inventors could show immunogenicity for HLA-B*07 restricted TUMAPs of the invention, demonstrating that these peptides are T-cell epitopes against which CD8+ precursor T cells exist in humans (Table 10a and 10b). 
     In Vitro Priming of CD8+ T Cells 
     In order to perform in vitro stimulations by artificial antigen presenting cells loaded with peptide-MHC complex (pMHC) and anti-CD28 antibody, the inventors first isolated CD8+ T cells from fresh HLA-B*07 leukapheresis products via positive selection using CD8 microbeads (Miltenyi Biotec, Bergisch-Gladbach, Germany) of healthy donors obtained from the University clinics Mannheim, Germany, after informed consent. 
     PBMCs and isolated CD8+ lymphocytes were incubated in T-cell medium (TCM) until use consisting of RPMI-Glutamax (Invitrogen, Karlsruhe, Germany) supplemented with 10% heat inactivated human AB serum (PAN-Biotech, Aidenbach, Germany), 100 U/ml Penicillin/100 μg/ml Streptomycin (Cambrex, Cologne, Germany), 1 mM sodium pyruvate (CC Pro, Oberdorla, Germany), 20 μg/ml Gentamycin (Cambrex). 2.5 ng/ml IL-7 (PromoCell, Heidelberg, Germany) and 10 U/ml IL-2 (Novartis Pharma, Nürnberg, Germany) were also added to the TCM at this step. 
     Generation of pMHC/anti-CD28 coated beads, T-cell stimulations and readout was performed in a highly defined in vitro system using four different pMHC molecules per stimulation condition and 8 different pMHC molecules per readout condition. 
     The purified co-stimulatory mouse IgG2a anti human CD28 Ab 9.3 (Jung et al., 1987) was chemically biotinylated using Sulfo-N-hydroxysuccinimidobiotin as recommended by the manufacturer (Perbio, Bonn, Germany). Beads used were 5.6 μm diameter streptavidin coated polystyrene particles (Bangs Laboratories, Illinois, USA). 
     pMHC used for positive and negative control stimulations were A*0201/MLA-001 (peptide ELAGIGILTV (SEQ ID NO. 446) from modified Melan-A/MART-1) and A*0201/DDX5-001 (YLLPAIVHI from DDX5, SEQ ID NO. 447), respectively. 
     800.000 beads/200 μl were coated in 96-well plates in the presence of 4×12.5 ng different biotin-pMHC, washed and 600 ng biotin anti-CD28 were added subsequently in a volume of 200 μl. Stimulations were initiated in 96-well plates by co-incubating 1×10 6  CD8+ T cells with 2×10 5  washed coated beads in 200 μl TCM supplemented with 5 ng/ml IL-12 (PromoCell) for 3 days at 37° C. Half of the medium was then exchanged by fresh TCM supplemented with 80 U/ml IL-2 and incubating was continued for four days at 37° C. This stimulation cycle was performed for a total of three times. For the pMHC multimer readout using 8 different pMHC molecules per condition, a two-dimensional combinatorial coding approach was used as previously described (Andersen et al., 2012) with minor modifications encompassing coupling to five different fluorochromes. Finally, multimeric analyses were performed by staining the cells with Live/dead near IR dye (Invitrogen, Karlsruhe, Germany), CD8-FITC antibody clone SK1 (BD, Heidelberg, Germany) and fluorescent pMHC multimers. For analysis, a BD LSRII SORP cytometer equipped with appropriate lasers and filters was used. Peptide specific cells were calculated as percentage of total CD8+ cells. Evaluation of multimeric analysis was done using the FlowJo software (Tree Star, Oreg., USA). In vitro priming of specific multimer+ CD8+ lymphocytes was detected by comparing to negative control stimulations. Immunogenicity for a given antigen was detected if at least one evaluable in vitro stimulated well of one healthy donor was found to contain a specific CD8+ T-cell line after in vitro stimulation (i.e. this well contained at least 1% of specific multimer+ among CD8+ T-cells and the percentage of specific multimer+ cells was at least 10× the median of the negative control stimulations). 
     In vitro immunogenicity for acute myeloid leukemia, breast cancer, cholangiocellular carcinoma, chronic lymphocytic leukemia, colorectal cancer, gallbladder cancer, glioblastoma, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, lung cancer (including non-small cell lung cancer adenocarcinoma, squamous cell non-small cell lung cancer, and small cell lung cancer), ovarian cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, urinary bladder carcinoma, uterine and endometrial cancer peptides. 
     For tested HLA class I peptides, in vitro immunogenicity could be demonstrated by generation of peptide specific T-cell lines. Exemplary flow cytometry results after TUMAP-specific multimer staining for two peptides of the invention are shown in  FIGS.  3 A through  3 G  together with corresponding negative controls. Results for 58 peptides from the invention are summarized in Table 10a and 10b. 
     
       
         
           
               
             
               
                 TABLE 10a 
               
             
            
               
                   
               
               
                 in vitro immunogenicity of HLA class I peptides of 
               
               
                 the invention 
               
               
                 Exemplary results of in vitro immunogenicity 
               
               
                 experiments conducted by the applicant for the 
               
               
                 peptides of the invention. &lt;20% = +;  
               
               
                 20% - 49% = ++; 50% - 69% = +++; &gt;= 70% = ++++ 
               
            
           
           
               
               
               
            
               
                 Seq ID No 
                 Sequence 
                 Wells positive [%] 
               
               
                   
               
               
                 388 
                 SPSVSQLSVL 
                 ++++ 
               
               
                   
               
               
                 389 
                 APLPRPGAVL 
                 ++ 
               
               
                   
               
               
                 390 
                 SPRMSGLLSQT 
                 +++ 
               
               
                   
               
               
                 391 
                 APRPASSL 
                 + 
               
               
                   
               
               
                 392 
                 GPQPWHAAL 
                 ++ 
               
               
                   
               
               
                 393 
                 APAAWLRSA 
                 +++ 
               
               
                   
               
               
                 396 
                 VPDVAQFVL 
                 ++ 
               
               
                   
               
               
                 398 
                 SPASRSISL 
                 + 
               
               
                   
               
               
                 399 
                 NPFYPEVEL 
                 + 
               
               
                   
               
               
                 405 
                 LPFDGPGGIL 
                 ++++ 
               
               
                   
               
               
                 406 
                 LPDGSRVEL 
                 ++++ 
               
               
                   
               
               
                 407 
                 FPRLVGPDF 
                 +++ 
               
               
                   
               
               
                 408 
                 YPKDIYSSF 
                 ++ 
               
               
                   
               
               
                 410 
                 SPRSWIQVQI 
                 + 
               
               
                   
               
               
                 411 
                 IPNWARQDL 
                 ++++ 
               
               
                   
               
               
                 414 
                 KPSESIYSAL 
                 ++ 
               
               
                   
               
               
                 415 
                 LPSDSHFKITF 
                 ++ 
               
               
                   
               
               
                 418 
                 RPMTPTQIGPSL 
                 + 
               
               
                   
               
               
                 419 
                 SPMWHVQQL 
                 ++++ 
               
               
                   
               
               
                 420 
                 SPRWLPVSL 
                 ++++ 
               
               
                   
               
               
                 423 
                 SPRVYWLGL 
                 ++++ 
               
               
                   
               
               
                 425 
                 YPRGNHWAVGHL 
                 ++ 
               
               
                   
               
               
                 427 
                 VPSSRILQL 
                 +++ 
               
               
                   
               
               
                 429 
                 RPRALRDLQL 
                 ++ 
               
               
                   
               
               
                 430 
                 RPRALRDLQLL 
                 +++ 
               
               
                   
               
               
                 433 
                 IPEPSAQQL 
                 + 
               
               
                   
               
               
                 437 
                 FPYPYAERL 
                 +++ 
               
               
                   
               
               
                 440 
                 YPRTITPGM 
                 + 
               
               
                   
               
               
                 443 
                 VPDGVSKVL 
                 +++ 
               
               
                   
               
               
                 445 
                 RPAATAVISL 
                 + 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10b 
               
             
            
               
                   
               
               
                 in vitro immunogenicity of HLA class I peptides of 
               
               
                 the invention 
               
               
                 Exemplary results of in vitro immunogenicity 
               
               
                 experiments conducted by the applicant for the 
               
               
                 peptides of the invention. &lt;20% = +; 
               
               
                 20% - 49% = ++; 50% - 69% = +++; &gt;= 70% = ++++ 
               
            
           
           
               
               
               
            
               
                 Seq ID No 
                 Sequence 
                 Wells positive [%] 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                 RPRSLQCVSL 
                 + 
               
               
                   
               
               
                 3 
                 MPYWLTAL 
                 + 
               
               
                   
               
               
                 4 
                 GPKKFIVKL 
                 + 
               
               
                   
               
               
                 5 
                 LPSLSHCSQL 
                 ++ 
               
               
                   
               
               
                 6 
                 LPLNSSTSL 
                 + 
               
               
                   
               
               
                 9 
                 RPDSRLLEL 
                 +++ 
               
               
                   
               
               
                 12 
                 LPNTGRIGQLL 
                 ++ 
               
               
                   
               
               
                 17 
                 SPAAPLSPASSL 
                 + 
               
               
                   
               
               
                 21 
                 APSRLLEL 
                 + 
               
               
                   
               
               
                 23 
                 VPRPTSTVGL 
                 ++ 
               
               
                   
               
               
                 24 
                 VPRPTSTVGLFL 
                 + 
               
               
                   
               
               
                 26 
                 SPSFSSTLLSL 
                 + 
               
               
                   
               
               
                 33 
                 LPRGLSPARQL 
                 ++ 
               
               
                   
               
               
                 38 
                 RPSFPNLTSF 
                 + 
               
               
                   
               
               
                 45 
                 TRPWSGPYIL 
                 + 
               
               
                   
               
               
                 48 
                 RPRYSIGL 
                 + 
               
               
                   
               
               
                 49 
                 APEKARAFL 
                 + 
               
               
                   
               
               
                 51 
                 SPVFYVQTL 
                 + 
               
               
                   
               
               
                 53 
                 SPRIPFSTF 
                 + 
               
               
                   
               
               
                 56 
                 LPALLRSGLTL 
                 +++ 
               
               
                   
               
               
                 59 
                 KPRTIYSSL 
                 + 
               
               
                   
               
               
                 61 
                 LPRIPFSTF 
                 ++ 
               
               
                   
               
               
                 64 
                 VPRPIFSQLYL 
                 +++ 
               
               
                   
               
               
                 68 
                 FPNEVSVVL 
                 ++ 
               
               
                   
               
               
                 361 
                 SPYGSDRLVQL 
                 + 
               
               
                   
               
               
                 364 
                 KPRTPFTTAQL 
                 + 
               
               
                   
               
               
                 365 
                 RPKHFLQML 
                 + 
               
               
                   
               
               
                 366 
                 SPTLRQLDL 
                 ++ 
               
               
                   
               
            
           
         
       
     
     Example 4 
     Synthesis of Peptides 
     All peptides were synthesized using standard and well-established solid phase peptide synthesis using the Fmoc-strategy. Identity and purity of each individual peptide have been determined by mass spectrometry and analytical RP-HPLC. The peptides were obtained as white to off-white lyophilizes (trifluoro acetate salt) in purities of &gt;50%. All TUMAPs are preferably administered as trifluoro-acetate salts or acetate salts, other salt-forms are also possible. 
     Example 5 
     MHC Binding Assays 
     Candidate peptides for T cell based therapies according to the present invention were further tested for their MHC binding capacity (affinity). The individual peptide-MHC complexes were produced by UV-ligand exchange, where a UV-sensitive peptide is cleaved upon UV-irradiation and exchanged with the peptide of interest as analyzed. Only peptide candidates that can effectively bind and stabilize the peptide-receptive MHC molecules prevent dissociation of the MHC complexes. To determine the yield of the exchange reaction, an ELISA was performed based on the detection of the light chain (β2m) of stabilized MHC complexes. The assay was performed as generally described in Rodenko et al. (Rodenko et al., 2006) 
     96 well MAXISorp plates (NUNC) were coated over night with 2 ug/ml streptavidin in PBS at room temperature, washed 4× and blocked for 1 h at 37° C. in 2% BSA containing blocking buffer. Refolded HLA-A*02:01/MLA-001 monomers served as standards, covering the range of 15-500 ng/ml. Peptide-MHC monomers of the UV-exchange reaction were diluted 100-fold in blocking buffer. Samples were incubated for 1 h at 37° C., washed four times, incubated with 2 ug/ml HRP conjugated anti-β2m for 1 h at 37° C., washed again and detected with TMB solution that is stopped with NH 2 SO 4 . Absorption was measured at 450 nm. Candidate peptides that show a high exchange yield (preferably higher than 50%, most preferred higher than 75%) are generally preferred for a generation and production of antibodies or fragments thereof, and/or T cell receptors or fragments thereof, as they show sufficient avidity to the MHC molecules and prevent dissociation of the MHC complexes. 
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 MHC class I binding scores. Binding of HLA-class I 
               
               
                 restricted peptides to HLA-B*07 was ranged by pep- 
               
               
                 tide exchange yield: &gt;10% = +; &gt;20% = ++; 
               
               
                 &gt;50 = +++; &gt; 75% = ++++ 
               
            
           
           
               
               
               
            
               
                 SEQ 
                   
                 Peptide 
               
               
                 ID 
                 Sequence 
                 exchange 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                 RPRSLQCVSL 
                 ++++ 
               
               
                   
               
               
                 2 
                 VPGSDPARYEFL 
                 +++ 
               
               
                   
               
               
                 3 
                 MPYVVLTAL 
                 ++++ 
               
               
                   
               
               
                 4 
                 GPKKFIVKL 
                 +++ 
               
               
                   
               
               
                 5 
                 LPSLSHCSQL 
                 ++++ 
               
               
                   
               
               
                 6 
                 LPLNSSTSL 
                 ++++ 
               
               
                   
               
               
                 7 
                 RPSQLAPATL 
                 +++ 
               
               
                   
               
               
                 8 
                 MPKTNLSKM 
                 +++ 
               
               
                   
               
               
                 9 
                 RPDSRLLEL 
                 ++++ 
               
               
                   
               
               
                 10 
                 SPMEAELVRRIL 
                 ++++ 
               
               
                   
               
               
                 11 
                 APLPRPGAV 
                 ++++ 
               
               
                   
               
               
                 12 
                 LPNTGRIGQLL 
                 ++++ 
               
               
                   
               
               
                 13 
                 LPNTGRIGQL 
                 +++ 
               
               
                   
               
               
                 14 
                 AVHEIGHSL 
                 +++ 
               
               
                   
               
               
                 15 
                 KPGFNISIL 
                 ++++ 
               
               
                   
               
               
                 16 
                 FPAPPAHWF 
                 ++++ 
               
               
                   
               
               
                 17 
                 SPAAPLSPASSL 
                 ++++ 
               
               
                   
               
               
                 18 
                 MALSVLRLAL 
                 ++ 
               
               
                   
               
               
                 19 
                 WPRLPGAGL 
                 +++ 
               
               
                   
               
               
                 20 
                 MVLGIGPVL 
                 ++++ 
               
               
                   
               
               
                 21 
                 APSRLLEL 
                 ++++ 
               
               
                   
               
               
                 22 
                 LPQLKPAL 
                 ++++ 
               
               
                   
               
               
                 23 
                 VPRPTSTVGL 
                 +++ 
               
               
                   
               
               
                 24 
                 VPRPTSTVGLFL 
                 ++++ 
               
               
                   
               
               
                 25 
                 RPQGAVGGL 
                 +++ 
               
               
                   
               
               
                 26 
                 SPSFSSTLLSL 
                 ++++ 
               
               
                   
               
               
                 27 
                 RIRVTSEVL 
                 +++ 
               
               
                   
               
               
                 28 
                 LPAPTSLVL 
                 ++++ 
               
               
                   
               
               
                 29 
                 APLRVHITSL 
                 ++++ 
               
               
                   
               
               
                 30 
                 YPGFTKRL 
                 +++ 
               
               
                   
               
               
                 31 
                 RPGPSDPAA 
                 +++ 
               
               
                   
               
               
                 32 
                 APMAPGRSPL 
                 ++++ 
               
               
                   
               
               
                 33 
                 LPRGLSPARQL 
                 +++ 
               
               
                   
               
               
                 34 
                 APMAPGRSP 
                 +++ 
               
               
                   
               
               
                 35 
                 APLPPPRAL 
                 +++ 
               
               
                   
               
               
                 36 
                 RPFSREMDL 
                 +++ 
               
               
                   
               
               
                 37 
                 LPPPRALTL 
                 +++ 
               
               
                   
               
               
                 38 
                 RPSFPNLTSF 
                 ++++ 
               
               
                   
               
               
                 39 
                 QPRPSSEKI 
                 +++ 
               
               
                   
               
               
                 40 
                 FPRTVKHIDAAL 
                 ++++ 
               
               
                   
               
               
                 41 
                 MPAGGGPRSL 
                 ++++ 
               
               
                   
               
               
                 42 
                 APLKMLAL 
                 ++++ 
               
               
                   
               
               
                 43 
                 APTPRPKVL 
                 ++++ 
               
               
                   
               
               
                 44 
                 SPSQTVQRAV 
                 ++++ 
               
               
                   
               
               
                 45 
                 TRPWSGPYIL 
                 +++ 
               
               
                   
               
               
                 46 
                 QPISGNPVTL 
                 +++ 
               
               
                   
               
               
                 47 
                 RPRQTGALM 
                 ++++ 
               
               
                   
               
               
                 48 
                 RPRYSIGL 
                 +++ 
               
               
                   
               
               
                 49 
                 APEKARAFL 
                 +++ 
               
               
                   
               
               
                 50 
                 PEKARAFL 
                 +++ 
               
               
                   
               
               
                 51 
                 SPVFYVQTL 
                 ++++ 
               
               
                   
               
               
                 52 
                 KEDNPSGHTYTL 
                 +++ 
               
               
                   
               
               
                 53 
                 SPRIPFSTF 
                 ++++ 
               
               
                   
               
               
                 54 
                 VPSCGRSVEGL 
                 +++ 
               
               
                   
               
               
                 56 
                 LPALLRSGLTL 
                 ++++ 
               
               
                   
               
               
                 59 
                 KPRTIYSSL 
                 ++++ 
               
               
                   
               
               
                 60 
                 RPYSIYPHGVTF 
                 ++++ 
               
               
                   
               
               
                 61 
                 LPRIPFSTF 
                 ++++ 
               
               
                   
               
               
                 62 
                 KPQSTISGL 
                 +++ 
               
               
                   
               
               
                 63 
                 FPHMATTAF 
                 +++ 
               
               
                   
               
               
                 64 
                 VPRPIFSQLYL 
                 ++++ 
               
               
                   
               
               
                 65 
                 FPNVYSTLVL 
                 ++++ 
               
               
                   
               
               
                 66 
                 LPMTVISVL 
                 ++++ 
               
               
                   
               
               
                 67 
                 VPVSRPVL 
                 ++++ 
               
               
                   
               
               
                 68 
                 FPNEVSVVL 
                 ++++ 
               
               
                   
               
               
                 69 
                 RPEDGRPRL 
                 +++ 
               
               
                   
               
               
                 70 
                 VPAQRLGLL 
                 ++++ 
               
               
                   
               
               
                 71 
                 APFAPLHGGGSL 
                 +++ 
               
               
                   
               
               
                 72 
                 APCNGNVAV 
                 +++ 
               
               
                   
               
               
                 73 
                 LPVSSPVTL 
                 ++++ 
               
               
                   
               
               
                 74 
                 VPVSHPVL 
                 ++++ 
               
               
                   
               
               
                 75 
                 HVRPQTNCI 
                 +++ 
               
               
                   
               
               
                 76 
                 KPKVESQAL 
                 ++++ 
               
               
                   
               
               
                 77 
                 QPRLVPGETL 
                 ++++ 
               
               
                   
               
               
                 78 
                 HPSQESPTL 
                 +++ 
               
               
                   
               
               
                 79 
                 GPASDHPSL 
                 +++ 
               
               
                   
               
               
                 80 
                 SALPTTISF 
                 +++ 
               
               
                   
               
               
                 81 
                 IAYPSLREAAL 
                 ++ 
               
               
                   
               
               
                 83 
                 AVSSHHNVI 
                 ++ 
               
               
                   
               
               
                 84 
                 MPMQDIKMI 
                 +++ 
               
               
                   
               
               
                 85 
                 MPMQDIKMILKM 
                 +++ 
               
               
                   
               
               
                 86 
                 ALLLRGVTL 
                 ++ 
               
               
                   
               
               
                 87 
                 APVGGNVTSSF 
                 +++ 
               
               
                   
               
               
                 88 
                 KPSAVKDSIY 
                 ++ 
               
               
                   
               
               
                 89 
                 FLIPRAGWLAGL 
                 ++ 
               
               
                   
               
               
                 91 
                 FPRLVGPDFF 
                 ++++ 
               
               
                   
               
               
                 92 
                 TSPLPPTV 
                 +++ 
               
               
                   
               
               
                 93 
                 SVAIAHGVF 
                 ++++ 
               
               
                   
               
               
                 94 
                 LPMSKRQEY 
                 +++ 
               
               
                   
               
               
                 95 
                 RTKEEINEL 
                 ++ 
               
               
                   
               
               
                 96 
                 QPSLVQAIF 
                 ++++ 
               
               
                   
               
               
                 98 
                 FPCSALLACF 
                 ++++ 
               
               
                   
               
               
                 99 
                 MPVSAFTVI 
                 ++++ 
               
               
                   
               
               
                 101 
                 KPGLPGLK 
                 + 
               
               
                   
               
               
                 102 
                 MAGPAIHTAPM 
                 ++ 
               
               
                   
               
               
                 103 
                 REPIMKADML 
                 ++ 
               
               
                   
               
               
                 104 
                 RPLPNSVIHV 
                 +++ 
               
               
                   
               
               
                 105 
                 RPRYETGVCA 
                 ++++ 
               
               
                   
               
               
                 106 
                 APFHIDRLF 
                 +++ 
               
               
                   
               
               
                 108 
                 APRGSPPI 
                 +++ 
               
               
                   
               
               
                 109 
                 LPRALMRST 
                 +++ 
               
               
                   
               
               
                 110 
                 YPSSPASAV 
                 ++++ 
               
               
                   
               
               
                 111 
                 YPLQQTNVY 
                 + 
               
               
                   
               
               
                 112 
                 YPSPLNKHSF 
                 +++ 
               
               
                   
               
               
                 113 
                 KPHLDRRGAVI 
                 ++++ 
               
               
                   
               
               
                 114 
                 FVPPSGPSNPM 
                 ++ 
               
               
                   
               
               
                 115 
                 KTKSLAQQL 
                 +++ 
               
               
                   
               
               
                 117 
                 IPHQRSSL 
                 ++++ 
               
               
                   
               
               
                 118 
                 NPERHKPSF 
                 +++ 
               
               
                   
               
               
                 119 
                 KATEYVHSL 
                 + 
               
               
                   
               
               
                 120 
                 TVRPKNAAL 
                 +++ 
               
               
                   
               
               
                 121 
                 GPFQRAAL 
                 +++ 
               
               
                   
               
               
                 122 
                 KPRTPFTTAQLL 
                 ++++ 
               
               
                   
               
               
                 123 
                 RPRLRDLPAL 
                 +++ 
               
               
                   
               
               
                 125 
                 SPAKQFNIY 
                 ++ 
               
               
                   
               
               
                 126 
                 MPREDAHF 
                 + 
               
               
                   
               
               
                 127 
                 KSKQVITLL 
                 + 
               
               
                   
               
               
                 129 
                 MTLPATTLTL 
                 ++ 
               
               
                   
               
               
                 130 
                 GAYDKARYL 
                 ++ 
               
               
                   
               
               
                 131 
                 MPFRNIRSIL 
                 +++ 
               
               
                   
               
               
                 132 
                 LPRLPVGSLV 
                 ++++ 
               
               
                   
               
               
                 133 
                 LPELPTTLTF 
                 ++ 
               
               
                   
               
               
                 134 
                 VAAAARLTL 
                 +++ 
               
               
                   
               
               
                 135 
                 MPRLLRLSL 
                 +++ 
               
               
                   
               
               
                 136 
                 QPDHAGIFRVF 
                 ++++ 
               
               
                   
               
               
                 139 
                 LVILQHQAM 
                 +++ 
               
               
                   
               
               
                 140 
                 TPFPDIHWF 
                 ++++ 
               
               
                   
               
               
                 141 
                 YGPYGSGSGW 
                 ++ 
               
               
                   
               
               
                 143 
                 YPMIPPAQL 
                 +++ 
               
               
                   
               
               
                 144 
                 RPVQGIPTY 
                 +++ 
               
               
                   
               
               
                 145 
                 VPAQRLGLLL 
                 +++ 
               
               
                   
               
               
                 146 
                 SPTRGSEF 
                 ++++ 
               
               
                   
               
               
                 147 
                 HVAQPAVVL 
                 +++ 
               
               
                   
               
               
                 149 
                 SPSSVFTSK 
                 +++ 
               
               
                   
               
               
                 150 
                 APLHGGGSL 
                 +++ 
               
               
                   
               
               
                 151 
                 QPTWNTQTRL 
                 ++++ 
               
               
                   
               
               
                 152 
                 SSASFSSELFRH 
                 +++ 
               
               
                   
               
               
                 153 
                 QPVHSLCSA 
                 ++++ 
               
               
                   
               
               
                 154 
                 RPPPSRRAVL 
                 +++ 
               
               
                   
               
               
                 156 
                 GSRPVTGSV 
                 +++ 
               
               
                   
               
               
                 157 
                 RPVTGSVC 
                 ++++ 
               
               
                   
               
               
                 158 
                 SVPVATVEL 
                 ++ 
               
               
                   
               
               
                 160 
                 IPVSHPVLTF 
                 ++ 
               
               
                   
               
               
                 161 
                 ASKILETSL 
                 ++ 
               
               
                   
               
               
                 162 
                 IPIRVDQNGAF 
                 +++ 
               
               
                   
               
               
                 164 
                 RAAGRRLQL 
                 ++++ 
               
               
                   
               
               
                 165 
                 RPSKEMQVTI 
                 ++++ 
               
               
                   
               
               
                 167 
                 NVNPARKGL 
                 ++++ 
               
               
                   
               
               
                 168 
                 SPSGQRDVSL 
                 ++++ 
               
               
                   
               
               
                 169 
                 RPFSVSSISQL 
                 ++++ 
               
               
                   
               
               
                 170 
                 APEGKRLGF 
                 ++++ 
               
               
                   
               
               
                 171 
                 LPLGGHKSL 
                 +++ 
               
               
                   
               
               
                 172 
                 SAQSLHPVL 
                 +++ 
               
               
                   
               
               
                 173 
                 VIINNPISL 
                 ++ 
               
               
                   
               
               
                 174 
                 IPVTSSVTL 
                 ++++ 
               
               
                   
               
               
                 176 
                 QPLDICHSF 
                 ++++ 
               
               
                   
               
               
                 177 
                 VWEPQGSSRSL 
                 +++ 
               
               
                   
               
               
                 178 
                 VPYYPRANL 
                 +++ 
               
               
                   
               
               
                 180 
                 RLRDYISSL 
                 ++++ 
               
               
                   
               
               
                 181 
                 LPVSPARAL 
                 +++ 
               
               
                   
               
               
                 182 
                 RPLPVSPARAL 
                 +++ 
               
               
                   
               
               
                 183 
                 VPRRPARAL 
                 +++ 
               
               
                   
               
               
                 184 
                 KIIASGNHL 
                 ++ 
               
               
                   
               
               
                 185 
                 RPVLTASSF 
                 ++++ 
               
               
                   
               
               
                 186 
                 VPLPAGGGTVLT 
                 + 
               
               
                   
               
               
                 187 
                 APPPPPPPF 
                 ++++ 
               
               
                   
               
               
                 188 
                 HAAASFETL 
                 ++ 
               
               
                   
               
               
                 189 
                 QPQCSTHIL 
                 ++++ 
               
               
                   
               
               
                 190 
                 RLAHVRARL 
                 +++ 
               
               
                   
               
               
                 191 
                 KPKAVKPKAA 
                 ++++ 
               
               
                   
               
               
                 192 
                 IPFADVKSF 
                 ++ 
               
               
                   
               
               
                 193 
                 LPALKEEAF 
                 ++++ 
               
               
                   
               
               
                 194 
                 HPNKIKASL 
                 +++ 
               
               
                   
               
               
                 195 
                 NPIFGRKEL 
                 +++ 
               
               
                   
               
               
                 196 
                 RPSGTAGAAL 
                 +++ 
               
               
                   
               
               
                 197 
                 RPSGTAGAALLA 
                 ++ 
               
               
                   
               
               
                 198 
                 LPSPAHAFRAL 
                 +++ 
               
               
                   
               
               
                 199 
                 SPFWIHQA 
                 ++ 
               
               
                   
               
               
                 201 
                 LPIARVLTV 
                 ++++ 
               
               
                   
               
               
                 202 
                 SPSREASAL 
                 +++ 
               
               
                   
               
               
                 203 
                 KPRGPIDI 
                 ++ 
               
               
                   
               
               
                 204 
                 FPYSGDKILV 
                 +++ 
               
               
                   
               
               
                 206 
                 TPRIGPKVSL 
                 +++ 
               
               
                   
               
               
                 207 
                 VPSDITTAF 
                 +++ 
               
               
                   
               
               
                 208 
                 RNRQVATAL 
                 +++ 
               
               
                   
               
               
                 209 
                 KIEQIRAVL 
                 +++ 
               
               
                   
               
               
                 210 
                 IPENRVVSY 
                 ++ 
               
               
                   
               
               
                 211 
                 IPDTIASVL 
                 +++ 
               
               
                   
               
               
                 212 
                 VPYAAQAAL 
                 ++++ 
               
               
                   
               
               
                 213 
                 RPYQDAPVA 
                 ++++ 
               
               
                   
               
               
                 214 
                 LPLKFFPII 
                 + 
               
               
                   
               
               
                 215 
                 IPVAIKEL 
                 ++ 
               
               
                   
               
               
                 216 
                 LPWEQNEQV 
                 +++ 
               
               
                   
               
               
                 217 
                 SPGDKRLAAYL 
                 +++ 
               
               
                   
               
               
                 219 
                 VPHTGRYTCL 
                 +++ 
               
               
                   
               
               
                 220 
                 RPAPGPAPFV 
                 +++ 
               
               
                   
               
               
                 221 
                 LPQRPNARL 
                 +++ 
               
               
                   
               
               
                 222 
                 MLKTTLTAF 
                 + 
               
               
                   
               
               
                 223 
                 KAHVRIEL 
                 ++ 
               
               
                   
               
               
                 224 
                 SPIIHSILL 
                 ++++ 
               
               
                   
               
               
                 225 
                 SPIIHSIL 
                 +++ 
               
               
                   
               
               
                 226 
                 APGGSSRSSL 
                 +++ 
               
               
                   
               
               
                 227 
                 RPGTGQGGL 
                 +++ 
               
               
                   
               
               
                 228 
                 RPTAASQSRAL 
                 +++ 
               
               
                   
               
               
                 229 
                 FPNAGPRHLL 
                 +++ 
               
               
                   
               
               
                 230 
                 DVIDDIISL 
                 ++++ 
               
               
                   
               
               
                 231 
                 SPITLQAL 
                 ++++ 
               
               
                   
               
               
                 232 
                 TAYPSLRLL 
                 +++ 
               
               
                   
               
               
                 233 
                 MAYDRFIAI 
                 +++ 
               
               
                   
               
               
                 234 
                 HPRAPGEQQRL 
                 +++ 
               
               
                   
               
               
                 235 
                 AQNPAGTAL 
                 + 
               
               
                   
               
               
                 236 
                 TPELKSSIL 
                 +++ 
               
               
                   
               
               
                 237 
                 LPRAGGAF 
                 ++++ 
               
               
                   
               
               
                 238 
                 LPRAGGAFLM 
                 ++++ 
               
               
                   
               
               
                 239 
                 VLPRAGGAFLM 
                 +++ 
               
               
                   
               
               
                 240 
                 RVMLPKAAL 
                 +++ 
               
               
                   
               
               
                 242 
                 IPETASVVAI 
                 +++ 
               
               
                   
               
               
                 243 
                 MARTGGMVVI 
                 ++ 
               
               
                   
               
               
                 244 
                 VPAHLVAA 
                 ++ 
               
               
                   
               
               
                 245 
                 GPVPSPLAL 
                 ++++ 
               
               
                   
               
               
                 246 
                 RPILKEQSSSSF 
                 ++++ 
               
               
                   
               
               
                 247 
                 SPVGVGQRL 
                 +++ 
               
               
                   
               
               
                 248 
                 KPYDGIPAS 
                 +++ 
               
               
                   
               
               
                 249 
                 SPRSGVLL 
                 +++ 
               
               
                   
               
               
                 250 
                 APAAPAAVPS 
                 ++ 
               
               
                   
               
               
                 251 
                 MPVDSFNSM 
                 ++++ 
               
               
                   
               
               
                 252 
                 QPENSLEGISL 
                 +++ 
               
               
                   
               
               
                 253 
                 MPVDSFNSML 
                 ++++ 
               
               
                   
               
               
                 254 
                 RVIQGTTTL 
                 ++++ 
               
               
                   
               
               
                 255 
                 VPSHWMVAL 
                 ++++ 
               
               
                   
               
               
                 256 
                 SPVPSHWMVAL 
                 ++++ 
               
               
                   
               
               
                 258 
                 SVIGPNSRL 
                 ++ 
               
               
                   
               
               
                 259 
                 VPMPGVQAV 
                 ++++ 
               
               
                   
               
               
                 260 
                 LVQSSRSEV 
                 ++++ 
               
               
                   
               
               
                 261 
                 SPSTSRTPL 
                 +++ 
               
               
                   
               
               
                 262 
                 SPSTSRTPLLSSL 
                 ++++ 
               
               
                   
               
               
                 263 
                 SQRPPATSQA 
                 ++ 
               
               
                   
               
               
                 264 
                 APRPGNWIL 
                 +++ 
               
               
                   
               
               
                 265 
                 FPRKPYEGRV 
                 +++ 
               
               
                   
               
               
                 266 
                 KPYEGRVEI 
                 ++++ 
               
               
                   
               
               
                 267 
                 MPVPGILL 
                 +++ 
               
               
                   
               
               
                 268 
                 EPLSVTASY 
                 ++ 
               
               
                   
               
               
                 269 
                 FTVSSSSAM 
                 ++ 
               
               
                   
               
               
                 270 
                 SPRGTTSTL 
                 +++ 
               
               
                   
               
               
                 271 
                 SPTPVFTTL 
                 +++ 
               
               
                   
               
               
                 272 
                 SSPRGTTSTL 
                 +++ 
               
               
                   
               
               
                 273 
                 TDTPSTTPTTI 
                 ++ 
               
               
                   
               
               
                 274 
                 KPIRTGISPLAL 
                 +++ 
               
               
                   
               
               
                 275 
                 IPAPQGAVL 
                 +++ 
               
               
                   
               
               
                 276 
                 RPVWDVRSA 
                 ++++ 
               
               
                   
               
               
                 277 
                 MPPLLIVAF 
                 ++ 
               
               
                   
               
               
                 278 
                 LIAARGSLVL 
                 +++ 
               
               
                   
               
               
                 279 
                 APADEPRTVL 
                 +++ 
               
               
                   
               
               
                 280 
                 LPRAFLQSL 
                 ++++ 
               
               
                   
               
               
                 281 
                 NPRSPPATM 
                 ++++ 
               
               
                   
               
               
                 282 
                 AVRLPTPNL 
                 ++++ 
               
               
                   
               
               
                 283 
                 RPQPGWRESL 
                 ++++ 
               
               
                   
               
               
                 284 
                 RPSAPRGPP 
                 ++++ 
               
               
                   
               
               
                 285 
                 RITWKGLLL 
                 +++ 
               
               
                   
               
               
                 286 
                 APARPAAAF 
                 ++++ 
               
               
                   
               
               
                 287 
                 SPIPRPLFL 
                 ++++ 
               
               
                   
               
               
                 288 
                 LHAMNSLSAM 
                 +++ 
               
               
                   
               
               
                 289 
                 LPYEKVSRL 
                 +++ 
               
               
                   
               
               
                 290 
                 RPTHPLRSF 
                 ++++ 
               
               
                   
               
               
                 291 
                 SPSKSLEM 
                 +++ 
               
               
                   
               
               
                 292 
                 LPMTHRLQL 
                 +++ 
               
               
                   
               
               
                 293 
                 FPYDKPLIM 
                 ++++ 
               
               
                   
               
               
                 294 
                 VPKPAIPSSSVL 
                 ++++ 
               
               
                   
               
               
                 295 
                 HPRWIEPTVM 
                 ++++ 
               
               
                   
               
               
                 296 
                 SPLLMQRTL 
                 ++++ 
               
               
                   
               
               
                 298 
                 RVLLRWISL 
                 +++ 
               
               
                   
               
               
                 299 
                 SPFSGGPVSF 
                 ++++ 
               
               
                   
               
               
                 300 
                 HPYSDLADVF 
                 +++ 
               
               
                   
               
               
                 301 
                 FPAFLEAM 
                 +++ 
               
               
                   
               
               
                 302 
                 IPIDQILNSF 
                 +++ 
               
               
                   
               
               
                 303 
                 RPPPPCIAL 
                 ++++ 
               
               
                   
               
               
                 304 
                 SPLIGDFPAF 
                 ++ 
               
               
                   
               
               
                 305 
                 AASPVGSAL 
                 +++ 
               
               
                   
               
               
                 306 
                 RPFPLALL 
                 +++ 
               
               
                   
               
               
                 307 
                 RPHQKGWLSI 
                 +++ 
               
               
                   
               
               
                 308 
                 RPDVVRTLL 
                 ++++ 
               
               
                   
               
               
                 309 
                 FAFYGGKSL 
                 +++ 
               
               
                   
               
               
                 310 
                 SPGWAQTQL 
                 ++++ 
               
               
                   
               
               
                 311 
                 APRLALDPDAL 
                 ++++ 
               
               
                   
               
               
                 312 
                 SPSLQSSRESL 
                 +++ 
               
               
                   
               
               
                 313 
                 VPLSSYVSI 
                 ++++ 
               
               
                   
               
               
                 314 
                 IALMKLAGPL 
                 ++ 
               
               
                   
               
               
                 315 
                 APVVFPAL 
                 ++++ 
               
               
                   
               
               
                 316 
                 NPREPEKSL 
                 +++ 
               
               
                   
               
               
                 317 
                 MPYNSAHHCVV 
                 ++++ 
               
               
                   
               
               
                 318 
                 TPISNTGVL 
                 ++++ 
               
               
                   
               
               
                 319 
                 RPLDTFRVL 
                 ++++ 
               
               
                   
               
               
                 320 
                 APMHIDRNIL 
                 ++++ 
               
               
                   
               
               
                 321 
                 QPQQPGFFL 
                 +++ 
               
               
                   
               
               
                 322 
                 RAVPVGSGL 
                 +++ 
               
               
                   
               
               
                 323 
                 TPHGITDIL 
                 ++++ 
               
               
                   
               
               
                 324 
                 LPAPLRISL 
                 ++++ 
               
               
                   
               
               
                 325 
                 SPRSNPVRL 
                 ++++ 
               
               
                   
               
               
                 327 
                 GPRTTQSSVL 
                 ++++ 
               
               
                   
               
               
                 328 
                 LPLHRGDLVI 
                 +++ 
               
               
                   
               
               
                 329 
                 QPANFIVLL 
                 +++ 
               
               
                   
               
               
                 330 
                 RPFSAIAEL 
                 ++++ 
               
               
                   
               
               
                 331 
                 SPDSAILKL 
                 +++ 
               
               
                   
               
               
                 332 
                 SPYAGSTAF 
                 ++++ 
               
               
                   
               
               
                 333 
                 SVLPRALSL 
                 +++ 
               
               
                   
               
               
                 334 
                 YPLSLALHF 
                 ++++ 
               
               
                   
               
               
                 335 
                 VPPQNPRPSL 
                 +++ 
               
               
                   
               
               
                 336 
                 YPLQGPGLLSV 
                 +++ 
               
               
                   
               
               
                 337 
                 IPTSRVITL 
                 ++++ 
               
               
                   
               
               
                 338 
                 MPATPSLKV 
                 +++ 
               
               
                   
               
               
                 339 
                 GPQRTTSV 
                 +++ 
               
               
                   
               
               
                 340 
                 APEPRAALL 
                 +++ 
               
               
                   
               
               
                 341 
                 LPRSPPLKVL 
                 ++++ 
               
               
                   
               
               
                 342 
                 RPRPPKVL 
                 +++ 
               
               
                   
               
               
                 343 
                 RPRPPKVLGL 
                 +++ 
               
               
                   
               
               
                 344 
                 VPYPSPTCV 
                 ++++ 
               
               
                   
               
               
                 345 
                 SAAPPGASL 
                 +++ 
               
               
                   
               
               
                 346 
                 IPMPRITWL 
                 ++++ 
               
               
                   
               
               
                 347 
                 SPLEKINSF 
                 ++++ 
               
               
                   
               
               
                 348 
                 HPAPPVTSA 
                 +++ 
               
               
                   
               
               
                 349 
                 QPRDGWPMML 
                 ++++ 
               
               
                   
               
               
                 350 
                 RPKSTLMNF 
                 ++++ 
               
               
                   
               
               
                 351 
                 SPYADIIPSA 
                 +++ 
               
               
                   
               
               
                 352 
                 LPAFSKIGGIL 
                 ++++ 
               
               
                   
               
               
                 353 
                 KPRATWTL 
                 +++ 
               
               
                   
               
               
                 354 
                 APAKDARASL 
                 ++++ 
               
               
                   
               
               
                 355 
                 APKTSFIAA 
                 ++++ 
               
               
                   
               
               
                 356 
                 RPFLRLPSL 
                 +++ 
               
               
                   
               
               
                 357 
                 LPPHIFAI 
                 ++ 
               
               
                   
               
               
                 358 
                 APSMLRKNQL 
                 +++ 
               
               
                   
               
               
                 359 
                 SPRRLVELAGQSL 
                 ++++ 
               
               
                   
               
               
                 360 
                 SPASRSISLL 
                 ++++ 
               
               
                   
               
               
                 361 
                 SPYGSDRLVQL 
                 ++++ 
               
               
                   
               
               
                 362 
                 KPMLPPAAF 
                 +++ 
               
               
                   
               
               
                 363 
                 KPRTPFTTA 
                 ++++ 
               
               
                   
               
               
                 364 
                 KPRTPFTTAQL 
                 ++++ 
               
               
                   
               
               
                 365 
                 RPKHFLQML 
                 ++++ 
               
               
                   
               
               
                 366 
                 SPTLRQLDL 
                 ++++ 
               
               
                   
               
               
                 367 
                 APQVHIFSL 
                 ++++ 
               
               
                   
               
               
                 368 
                 NPASRLTAL 
                 ++++ 
               
               
                   
               
               
                 369 
                 RPYGCVLRAA 
                 ++++ 
               
               
                   
               
               
                 370 
                 AAHEFGHVL 
                 ++ 
               
               
                   
               
               
                 371 
                 APRSPGQVTPRGL 
                 +++ 
               
               
                   
               
               
                 372 
                 SPSSASLTL 
                 ++++ 
               
               
                   
               
               
                 373 
                 LPKPDLPQLI 
                 + 
               
               
                   
               
               
                 374 
                 KPRNMTGLDL 
                 ++++ 
               
               
                   
               
               
                 375 
                 LPRGVLEGL 
                 ++++ 
               
               
                   
               
               
                 376 
                 FPQVGRTAL 
                 ++++ 
               
               
                   
               
               
                 377 
                 SPFSKRIKL 
                 +++ 
               
               
                   
               
               
                 378 
                 SPRQPRLDF 
                 ++++ 
               
               
                   
               
               
                 379 
                 GPRQVLFPL 
                 ++++ 
               
               
                   
               
               
                 380 
                 SPYPGSAAF 
                 ++++ 
               
               
                   
               
               
                 381 
                 APRPRLLLL 
                 +++ 
               
               
                   
               
               
                 382 
                 RPGPQRTTSV 
                 ++++ 
               
               
                   
               
               
                 383 
                 KPRATWTLKL 
                 +++ 
               
               
                   
               
               
                 448 
                 TVYGEPRKL 
                 ++ 
               
               
                   
               
               
                 449 
                 RPKTSVNLISSL 
                 ++++ 
               
               
                   
               
               
                 450 
                 SAAARALLP 
                 + 
               
               
                   
               
               
                 451 
                 VPILPLNHAL 
                 ++++ 
               
               
                   
               
               
                 452 
                 QPVKKNTL 
                 ++++ 
               
               
                   
               
               
                 453 
                 APALPGQVTI 
                 ++++ 
               
               
                   
               
               
                 454 
                 SPDPAHLESL 
                 ++++ 
               
               
                   
               
               
                 455 
                 FPVQATIDF 
                 ++++ 
               
               
                   
               
               
                 456 
                 VPVSHPVLTL 
                 +++ 
               
               
                   
               
               
                 457 
                 RPPLSQRHTF 
                 ++++ 
               
               
                   
               
               
                 458 
                 VPIPTHYFVVL 
                 ++++ 
               
               
                   
               
               
                 459 
                 SPAPWRPWI 
                 ++++ 
               
               
                   
               
               
                 460 
                 APLMPLGKTL 
                 ++++ 
               
               
                   
               
               
                 461 
                 MPHLGPGILL 
                 ++++ 
               
               
                   
               
               
                 462 
                 MPLLADVRL 
                 ++++ 
               
               
                   
               
               
                 463 
                 LPTDLFNSVM 
                 ++++ 
               
               
                   
               
               
                 464 
                 VPFVPRTSV 
                 +++ 
               
               
                   
               
               
                 465 
                 VPKSLPYVL 
                 ++++ 
               
               
                   
               
               
                 466 
                 SPMEAILVSRL 
                 ++++ 
               
               
                   
               
               
                 467 
                 VPRNQDWLGVSRQL 
                 ++++ 
               
               
                   
               
               
                 468 
                 LPSLHVLVL 
                 ++++ 
               
               
                   
               
               
                 469 
                 LPLDTRTSI 
                 ++++ 
               
               
                   
               
               
                 470 
                 RPNGEVKSEL 
                 ++++ 
               
               
                   
               
               
                 471 
                 LPLLAGTLLL 
                 ++ 
               
               
                   
               
               
                 472 
                 LPMPAITWY 
                 ++ 
               
               
                   
               
               
                 473 
                 LPGEREAAL 
                 ++++ 
               
               
                   
               
               
                 474 
                 VPKADLLTL 
                 ++++ 
               
               
                   
               
               
                 475 
                 IPLEIQKL 
                 + 
               
               
                   
               
               
                 476 
                 EPNPVEEIF 
                 ++ 
               
               
                   
               
               
                 477 
                 NPVPVITWYKDNRL 
                 ++++ 
               
               
                   
               
               
                 478 
                 APKFISPASQL 
                 ++++ 
               
               
                   
               
               
                 479 
                 APHAGGALL 
                 ++++ 
               
               
                   
               
               
                 480 
                 VPAAPTKAL 
                 +++ 
               
               
                   
               
               
                 481 
                 SPARALLLALA 
                 +++ 
               
               
                   
               
               
                 482 
                 QPSLKKIIL 
                 ++++ 
               
               
                   
               
               
                 483 
                 KPAAAGVKKVA 
                 +++ 
               
               
                   
               
               
                 484 
                 LPASAEPKGTM 
                 ++ 
               
               
                   
               
               
                 486 
                 TPTRPLPSA 
                 ++ 
               
               
                   
               
               
                 487 
                 IPWFIKTAF 
                 ++++ 
               
               
                   
               
               
                 488 
                 LPLGGLPLLI 
                 +++ 
               
               
                   
               
               
                 489 
                 WPNHIMLVL 
                 ++++ 
               
               
                   
               
               
                 490 
                 APRGPAQGEAA 
                 ++++ 
               
               
                   
               
               
                 491 
                 MPEADLKRIF 
                 ++ 
               
               
                   
               
               
                 492 
                 IPFSVDEI 
                 + 
               
               
                   
               
               
                 493 
                 LPLQQYKLV 
                 + 
               
               
                   
               
               
                 494 
                 LPLRAVNLNL 
                 +++ 
               
               
                   
               
               
                 495 
                 SPSYTQASL 
                 ++++ 
               
               
                   
               
               
                 496 
                 MPAVSGPGPLF 
                 +++ 
               
               
                   
               
               
                 497 
                 YVVKPLHPF 
                 +++ 
               
               
                   
               
               
                 498 
                 RPQPQPRPAL 
                 ++++ 
               
               
                   
               
               
                 499 
                 QPVLPSPAC 
                 ++++ 
               
               
                   
               
            
           
         
       
     
     REFERENCE LIST 
     
         
         Alcoser, S. Y. et al., BMC Biotechnol. 11 (2011): 124 
         Allison, J. P. et al., Science. 270 (1995): 932-933 
         Andersen, R. S. et al., Nat Protoc. 7 (2012): 891-902 
         Anderson, N. L. et al., J Proteome Res. 11 (2012): 1868-1878 
         Appay, V. et al., Eur J Immunol. 36 (2006): 1805-1814 
         Banchereau, J. et al., Cell. 106 (2001): 271-274 
         Beatty, G. et al., J Immunol. 166 (2001): 2276-2282 
         Beggs, J. D., Nature. 275 (1978): 104-109 
         Benjamini, Y. et al., Journal of the Royal Statistical Society Series B (Methodological). Vol. 57 (1995): 289-300 
         Boulter, J. M. et al., Protein Eng. 16 (2003): 707-711 
         Braumuller, H. et al., Nature. (2013) 
         Bray, F. et al., Int J Cancer. 132 (2013): 1133-1145 
         Brossart, P. et al., Blood. 90 (1997): 1594-1599 
         Bruckdorfer, T. et al., Curr Pharm Biotechnol. 5 (2004): 29-43 
         Card, K. F. et al., Cancer Immunol Immunother. 53 (2004): 345-357 
         Cohen, C. J. et al., J Mol Recognit. 16 (2003a): 324-332 
         Cohen, C. J. et al., J Immunol. 170 (2003b): 4349-4361 
         Cohen, S. N. et al., Proc Natl Acad Sci USA. 69 (1972): 2110-2114 
         Coligan, J. E. et al., Current Protocols in Protein Science. (1995) 
         Colombetti, S. et al., J Immunol. 176 (2006): 2730-2738 
         Dengjel, J. et al., Clin Cancer Res. 12 (2006): 4163-4170 
         Denkberg, G. et al., J Immunol. 171 (2003): 2197-2207 
         Falk, K. et al., Nature. 351 (1991): 290-296 
         Ferlay et al., GLOBOCAN 2012 v1 0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No 11 [Internet] (2013), http://globocan.iarc.fr 
         Follenzi, A. et al., Nat Genet. 25 (2000): 217-222 
         Fong, L. et al., Proc Natl Acad Sci USA. 98 (2001): 8809-8814 
         Forsey, R. W. et al., Biotechnol Lett. 31 (2009): 819-823 
         Gabrilovich, D. I. et al., Nat Med. 2 (1996): 1096-1103 
         Gattinoni, L. et al., Nat Rev Immunol. 6 (2006): 383-393 
         Gnjatic, S. et al., Proc Natl Acad Sci USA. 100 (2003): 8862-8867 
         Godkin, A. et al., Int Immunol. 9 (1997): 905-911 
         Gragert, L. et al., Hum Immunol. 74 (2013): 1313-1320 
         Green, M. R. et al., Molecular Cloning, A Laboratory Manual. 4th (2012) 
         Greenfield, E. A., Antibodies: A Laboratory Manual. 2nd (2014) 
         Gunawardana, C. et al., Br J Haematol. 142 (2008): 606-609 
         Gustafsson, C. et al., Trends Biotechnol. 22 (2004): 346-353 
         Hwang, M. L. et al., J Immunol. 179 (2007): 5829-5838 
         Jung, G. et al., Proc Natl Acad Sci USA. 84 (1987): 4611-4615 
         Kibbe, A. H., Handbook of Pharmaceutical Excipients. rd (2000) 
         Krieg, A. M., Nat Rev Drug Discov. 5 (2006): 471-484 
         Kuball, J. et al., Blood. 109 (2007): 2331-2338 
         Liddy, N. et al., Nat Med. 18 (2012): 980-987 
         Ljunggren, H. G. et al., J Exp Med. 162 (1985): 1745-1759 
         Longenecker, B. M. et al., Ann N Y Acad Sci. 690 (1993): 276-291 
         Lonsdale, J., Nat Genet. 45 (2013): 580-585 
         Lukas, T. J. et al., Proc Natl Acad Sci USA. 78 (1981): 2791-2795 
         Lundblad, R. L., Chemical Reagents for Protein Modification. 3rd (2004) 
         Meziere, C. et al., J Immunol. 159 (1997): 3230-3237 
         Molina, J. R. et al., Mayo Clin Proc. 83 (2008): 584-594 
         Morgan, R. A. et al., Science. 314 (2006): 126-129 
         Mortara, L. et al., Clin Cancer Res. 12 (2006): 3435-3443 
         Mueller, L. N. et al., J Proteome Res. 7 (2008): 51-61 
         Mueller, L. N. et al., Proteomics. 7 (2007): 3470-3480 
         Mumberg, D. et al., Proc Natl Acad Sci USA. 96 (1999): 8633-8638 
         Pinheiro, J. et al., nlme: Linear and Nonlinear Mixed Effects Models (http://CRANR-projectorg/package=nlme) (2015) 
         Plebanski, M. et al., Eur J Immunol. 25 (1995): 1783-1787 
         Porta, C. et al., Virology. 202 (1994): 949-955 
         Rammensee, H. et al., Immunogenetics. 50 (1999): 213-219 
         Rini, B. I. et al., Cancer. 107 (2006): 67-74 
         Rock, K. L. et al., Science. 249 (1990): 918-921 
         Rodenko, B. et al., Nat Protoc. 1 (2006): 1120-1132 
         Saiki, R. K. et al., Science. 239 (1988): 487-491 
         Schmitt, T. M. et al., Hum Gene Ther. 20 (2009): 1240-1248 
         Scholten, K. B. et al., Clin Immunol. 119 (2006): 135-145 
         Seeger, F. H. et al., Immunogenetics. 49 (1999): 571-576 
         Sherman, F. et al., Laboratory Course Manual for Methods in Yeast Genetics. (1986) 
         Silva, L. P. et al., Anal Chem. 85 (2013): 9536-9542 
         Singh-Jasuja, H. et al., Cancer Immunol Immunother. 53 (2004): 187-195 
         Small, E. J. et al., J Clin Oncol. 24 (2006): 3089-3094 
         Sturm, M. et al., BMC Bioinformatics. 9 (2008): 163 
         Teufel, R. et al., Cell Mol Life Sci. 62 (2005): 1755-1762 
         Thakkar, J. P. et al., Cancer Epidemiol Biomarkers Prev. 23 (2014): 1985-1996 
         Tran, T. T. et al., Photochem Photobiol. 90 (2014): 1136-1143 
         Walter, S. et al., J Immunol. 171 (2003): 4974-4978 
         Walter, S. et al., Nat Med. 18 (2012): 1254-1261 
         Willcox, B. E. et al., Protein Sci. 8 (1999): 2418-2423 
         World Cancer Report (2014) 
         Zaremba, S. et al., Cancer Res. 57 (1997): 4570-4577 
         Zufferey, R. et al., J Virol. 73 (1999): 2886-2892