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B*44 RESTRICTED PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST CANCERS AND RELATED METHODS

20230002464 · 2023-01-05

    Inventors

    Cpc classification

    International classification

    Abstract

    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.

    Claims

    1. A method of treating a patient who has prostate cancer, comprising administering to said patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of EENIVAIGI (SEQ ID NO: 11).

    2. The method of claim 1, wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell, for a period of time sufficient to activate said T cell.

    3. The method of claim 1, further comprising administering to said patient an adjuvant selected from anti-CD40 antibody, 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, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.

    4. The method of claim 3, wherein the adjuvant is IL-1.

    5. The method of claim 3, wherein the adjuvant is IL-2.

    6. The method of claim 3, wherein the adjuvant is IL-7.

    7. The method of claim 3, wherein the adjuvant is IL-12.

    8. The method of claim 3, wherein the adjuvant is IL-15.

    9. The method of claim 3, wherein the adjuvant is IL-21.

    10. The method of claim 3, wherein the adjuvant is IL-23.

    11. A method of eliciting an immune response in a patient who has prostate cancer, comprising administering to said patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of EENIVAIGI (SEQ ID NO: 11).

    12. The method of claim 11, wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell, for a period of time sufficient to activate said T cell.

    13. The method of claim 11, further comprising administering to said patient an adjuvant selected from anti-CD40 antibody, 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, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.

    14. The method of claim 13, wherein the adjuvant is IL-1.

    15. The method of claim 13, wherein the adjuvant is IL-2.

    16. The method of claim 13, wherein the adjuvant is IL-7.

    17. The method of claim 13, wherein the adjuvant is IL-12.

    18. The method of claim 13, wherein the adjuvant is IL-15.

    19. The method of claim 13, wherein the adjuvant is IL-21.

    20. The method of claim 13, wherein the adjuvant is IL-23.

    Description

    [0339] 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.

    [0340] FIGS. 1A through 1M 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*44 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; reproductive organs, breast, prostate: low 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=124 for normal samples, N=159 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 cent (central nerve); 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. 1A: Gene symbols: KRT13, KRT17, Peptide: TELEVKIRDW (SEQ ID NO.: 196), FIG. 1B: Gene symbol: VCAN, Peptide: VEAATVSKW (SEQ ID NO.: 225), FIG. 1C: Gene symbol: EGFR, Peptide: QEILHGAVRF (SEQ ID NO.: 253), FIG. 1D: Gene symbol: TRPS1, Peptide: VEEEISRHY (SEQ ID NO.: 283), FIG. 1E: Gene symbol: KRT16, Peptide: AEKNRRDAETW (SEQ ID NO.: 305), FIG. 1F: Gene symbols: ZNF761, ZNF765, Peptide: EECDKAYSF (SEQ ID NO.: 364), FIG. 1G: Gene symbol: RTP4, Peptide: QEAKPRATW (SEQ ID NO.: 409), FIG. 1H: Gene symbol: PRDM15, Peptide: NEVDGEYRY (SEQ ID NO.: 452), FIG. 1I: Gene symbol: FGD6, Peptide: SESKVFQLL (SEQ ID NO.: 453), FIG. 1J: Gene symbol: TRPM8, Peptide: DEIFTNDRRW (SEQ ID NO.: 3), FIG. 1K: Gene symbols: ALPP, ALPPL2, Peptide: AEALGAAKKL (SEQ ID NO.: 4), FIG. 1L: Gene symbol: NLRP4, Peptide: NESDRLVYF (SEQ ID NO.: 16) and FIG. 1M: Gene symbol: RGS13, Peptide: MEHSDENIQFW (SEQ ID NO.: 19).

    [0341] FIGS. 2A through 2U 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&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); 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. 2A: Gene symbol: MAGEA4, Peptide: KEVDPASNTYTL (SEQ ID No.: 1), FIG. 2B: Gene symbol: KLK2, Peptide: EEFLRPRSL (SEQ ID No.: 2), FIG. 2C: Gene symbol: MAGEA3, Peptide: ELMEVDPIGHLY (SEQ ID No.: 8), FIG. 2D: Gene symbol: MMP12, Peptide: EMPGGPVW (SEQ ID No.: 14), FIG. 2E: Gene symbol: ESR1, Peptide: AEPPILYSEY (SEQ ID No.: 34), FIG. 2F: Gene symbol: MAGEA1, Peptide: AETSYVKVLEY (SEQ ID No.: 84), FIG. 2G: Gene symbol: PRAME, Peptide: QTLKAMVQAW (SEQ ID No.: 86), FIG. 2H: Gene symbol: CTAG1A, CTAG1B, Peptide: KEFTVSGNIL (SEQ ID No.: 88), FIG. 2I: Gene symbol: MAGEB2, Peptide: EESLLSSWDF (SEQ ID No.: 91), FIG. 2J: Gene symbols: MAGEA10, MAGEA4, MAGEA9, MAGEA9B, Peptide: GEPRKLLTQDW (SEQ ID No.: 418), FIG. 2K: Gene symbol: MAGEC2, Peptide: VEFLLLKY (SEQ ID No.: 5), FIG. 2L: Gene symbol: ACPP, Peptide: AELVGPVIPQDW (SEQ ID No.: 6), FIG. 2M: Gene symbol: MAGEA10, Peptide: KEVDPTGHSF (SEQ ID No.: 12), FIG. 2N: Gene symbol: CTAG2, Peptide: MEAELVRRI (SEQ ID No.: 15), FIG. 2O: Gene symbol: MMP1, Peptide: REYNLHRVA (SEQ ID No.: 23), FIG. 2P: Gene symbol: FLT3, Peptide: REYEYDLKW (SEQ ID No.: 32), FIG. 2Q: Gene symbols: SSX3, SSX4, SSX4B, Peptide: SEKIVYVY (SEQ ID No.: 43), FIG. 2R: Gene symbol: ANKRD28, Peptide: DEVRALIF (SEQ ID No.: 48), FIG. 2S: Gene symbol: MAGEB1, Peptide: EDNPSGHTY (SEQ ID No.: 52), FIG. 2T: Gene symbol: PAK1IP1, Peptide: YEQVLFGF (SEQ ID No.: 63) and FIG. 2U: Gene symbol: DNAH17, Peptide: EEYQDSFERY (SEQ ID No.: 64).

    [0342] FIGS. 3A-3G show exemplary results of peptide-specific in vitro CD8+ T cell responses of a healthy HLA-B*44+ donor. CD8+ T cells were primed using artificial APCs coated with anti-CD28 mAb and HLA-B*44 in complex with SEQ ID NO: 469, peptide (SEAFPSRAL) (FIG. 3A, left panel), SEQ ID NO: 512 peptide (AEPLVGQRW) (FIG. 3B, left panel), SEQ ID NO: 9 peptide (MEVDPIGHLYIF) (FIG. 3C, left panel), SEQ ID NO: 11 peptide (EENIVAIGI) (FIG. 3D, left panel), SEQ ID NO: 17 peptide (SEIYQPRGF) (FIG. 3E, left panel), SEQ ID NO: 35 peptide (RELVHMINW) (FIG. 3F, left panel), SEQ ID NO: 41 peptide (EENTGKTYF) (FIG. 3G, left panel), respectively. After three cycles of stimulation, the detection of peptide-reactive cells was performed by 2D multimer staining with B*44/SEQ ID NO: 469 (FIG. 3A), B*44/SEQ ID NO: 512 (FIG. 3B), B*44/SEQ ID NO: 9 (FIG. 3C), B*44/SEQ ID NO: 11 (D), B*44/SEQ ID NO: 17 (E), B*44/SEQ ID NO: 35 (F) or B*44/SEQ ID NO: 41 (FIG. 3G). Right panels (FIGS. 3A through 3G) show control staining of cells stimulated with irrelevant B*44/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.

    EXAMPLES

    Example 1

    [0343] Identification and Quantitation of Tumor Associated Peptides Presented on the Cell Surface

    [0344] Tissue Samples

    [0345] Patients' tumor tissues were obtained from: Asterand (Detroit, Mich., USA & 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 (OCU) (Osaka, Japan), University Hospital Heidelberg (Heidelberg, Germany), 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 Tübingen (Tübingen, Germany). Normal tissues were obtained from Asterand (Detroit, Mich., USA & Royston, Herts, UK), BioServe (Beltsville, Md., USA), Capital BioScience Inc. (Rockville, Md., USA), Centre for Clinical Transfusion Medicine Tuebingen (Tübingen, Germany), Geneticist Inc. (Glendale, Calif., USA), University Hospital Heidelberg (Heidelberg, Germany), Kyoto Prefectural University of Medicine (KPUM) (Kyoto, Japan), ProteoGenex Inc. (Culver City, Calif., USA), Tissue Solutions Ltd (Glasgow, UK), University Hospital Tübingen (Tübingen, Germany).

    [0346] 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.

    [0347] Isolation of HLA Peptides from Tissue Samples

    [0348] 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.

    [0349] Mass Spectrometry Analyses

    [0350] 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.

    [0351] 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'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. 1A-1M.

    [0352] Table 8 shows 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. 2 for prostate cancer (PRCA), peptide SEQ ID No. 16 for gallbladder cancer (GBC), melanoma (MEL), and non-Hodgkin lymphoma (NHL)).

    TABLE-US-00010 TABLE 8 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 No. Sequence Peptide Presentation on cancer entities 1 KEVDPASNTYTL NSCLCsquam 2 EEFLRPRSL PRCA 3 DEIFTNDRRW PRCA 4 AEALGAAKKL UEC 5 VEFLLLKY HCC 6 AELVGPVIPQDW PRCA 7 SESDLVNFI PRCA 8 ELMEVDPIGHLY OSCAR 9 MEVDPIGHLYIF GBC, HCC, NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR 10 SEYPTKNYV NSCLCadeno 11 EENIVAIGI PRCA 12 KEVDPTGHSF GBC, MEL 13 VEAQDRETW RCC 14 EMPGGPVW CRC, UBC 15 MEAELVRRI MEL 16 NESDRLVYF GBC, MEL, NHL 17 SEIYQPRGF NHL 18 QEAPRPASSL NSCLCsquam 19 MEHSDENIQFW NHL 20 LEALLSDLF BRCA, CRC, GC, NHL, NSCLCadeno, NSCLCsquam, OSCAR, UBC, UEC 21 SEAKEIKSQL BRCA 22 TEEITEGVW AML, CLL, HNSCC, NSCLCadeno 23 REYNLHRVA HNSCC 24 EELALRIGL CCC 25 SEKEPGQQY HCC 26 EESSSPVDEY GBC, RCC 27 GETCVRITY MEL 28 QEFPAHSL CLL 29 TENPKKFKI MEL 30 EEFCFSVRF AML 31 MESAKETRY BRCA, UEC 32 REYEYDLKW AML 33 IEYENQKRL AML 34 AEPPILYSEY UEC 35 RELVHMINW BRCA, UEC 36 LEQASRIWSW MEL 37 IEQGRWLW GBC, NHL 38 DEVRFFKGNKY OSCAR 39 AEAMGKFKQCF UEC 40 REVDPDDSYVF MEL 41 EENTGKTYF HNSCC, OSCAR 42 SEENTGKTYF HNSCC, NSCLCsquam, OSCAR 43 SEKIVYVY HCC 44 SEFGAPRW CCC 46 SELGLPKEV HNSCC 47 TEVHSSPAQRW NHL, UBC 48 DEVRALIF HCC 49 SEYVHSSF BRCA 50 SEYVHSSFSGF NSCLCadeno 51 VEMTGKHQL AML 52 EDNPSGHTY GBC, NHL 53 KEDNPSGHTY NHL 54 QEISAHRTEF CLL 55 TEFHMQFSY CLL 56 ALEEGGGYIF HCC 57 SEATHHTI AML, PACA 58 KEMDPSRQSY HCC 59 AEIEADRSYQ HNSCC 60 EEAVRSVAF CLL, NHL 61 AEYSVHKI PACA 62 AEYSVHKITSTF HNSCC 63 YEQVLFGF CLL 64 EEYQDSFERY HNSCC, OSCAR 65 SESMVESKF MEL, NSCLCadeno 66 AEVTLNNTI NSCLCadeno 67 TEGAVEVKY HCC 68 NEIDIHSIYF OSCAR 69 DENIQKFIW HNSCC, UBC 70 AEAEEAMKRL HNSCC 71 AEVGDIIKV NSCLCadeno, PACA 72 AEVGDIIKVHF HCC 73 GEGTLRLSW MEL 75 LETSCGSSTAY NSCLCadeno 76 RLNEHPSNNW PACA 77 QETLAESTW NHL 78 TEFSNHINL BRCA 79 TEAQRLDCW MEL 80 TEQSLYYRQW MEL 81 GEKATMQNL NSCLCsquam, UBC 82 AVFDESKSW HCC, OSCAR 83 TEGGTQKTF CCC, HCC, NHL, OSCAR 84 AETSYVKVLEY GBC 89 KEFYPVKEF OC 92 KEPSQSCIAQY OSCAR 93 SEAGLTANQY NHL 94 SLAELIAKDW CCC, HCC, UBC, UEC 95 AAFEDAQGHIW PACA 96 MDELEEGESY NHL 97 ELVHMINW BRCA 98 SEESAGPLL BRCA 99 SECVKSLSF BRCA 100 QGDWDYSFY AML 101 SEENTGKTY OSCAR 102 TELADLDAAW OC 103 AELFLTKSF HNSCC, NSCLCsquam 104 EVHSSPAQRW UBC 106 SVISDSPRSW OSCAR 107 YQENPRAAW MEL, PACA 108 QETNKVETY OSCAR 109 AFSPAAGNTW CCC 110 EVEVGEVKSW HCC 112 AEIEADRSYQH HNSCC, OSCAR 113 MEFKTLNKN MEL 115 QEPFTRPVL NSCLCsquam 118 SEVPVDSHYY GBC 120 VTEGAVEVKY AML, BRCA, CRC, NSCLCadeno, OC 121 YENIPVDKV MEL 122 GESVSWHLF HNSCC 123 DEINHQSL NHL 126 SEASQSPQY UEC 128 TELTEARVQVW MEL 129 EEAMKRLSY HNSCC, OSCAR 131 RESHLTEIRQY BRCA, PRCA 133 IEAPKLMW HNSCC, MEL, NSCLCadeno 134 IEIKDRLQL CLL 135 QEIDRGQYI MEL 136 EEMPEEIHL HNSCC, OSCAR 137 EKGLISAF SCLC 138 KEAPNIVTL BRCA 139 AESDFSNNML MEL 141 SEKWFRMGF AML 142 QELFLHPVL NHL 143 HEHIRSHW CRC, HCC, UEC 144 IEAYLERIGY BRCA 145 EELRMLSF CLL 146 MEELRMLSF CLL 147 RMLSFQQMTW NHL 148 KESDAGRYY CLL, NHL 149 AETEPERHLG CLL 151 TELQIPSF RCC 152 HENLIEDF HCC, OSCAR 153 IEIILLSGSL PACA 155 TEDARHPESW CLL, NHL 156 DAIPPPTLTW UBC 158 VEEERYTGQW UBC 159 EEVQDGKVI CCC, HNSCC, NSCLCadeno, OSCAR, PACA 160 AEIATTGQLY GBM, MEL 161 GESSEVKAVL AML 162 EAYDIELNKW OSCAR, UBC 164 DEDGKIVGY HCC 165 EEIEAHIAL AML, CCC 166 EEQDFINNRY GBM 167 AETENRYCV PACA 168 EEGPSVPKIY CLL, NHL 169 KEHNSSVPWSS RCC 171 WEWHTVF GC, NSCLCsquam, OSCAR 172 RENPGMFSW MEL 174 DENDAGNLITF OSCAR 175 NLKSPIPLW GBM, MEL, PACA, UBC 176 GETQQHIQL NSCLCsquam 177 LEEPMPFFY OSCAR 178 MEGAALLKIF PACA 179 EEHIFSAF NHL, NSCLCsquam, OSCAR 180 EEHSSKLQTSL UBC 181 HEVAQDDHL UBC 182 EELHAALSEW CRC, GBC, GC 183 KEMQVTISQQL NSCLCadeno 184 EEQLLQKVM AML 185 TEANVQALF CLL, NHL 186 EEIFAHLGL AML 187 TEQALRLSV PACA 188 AEFVPKADLL NSCLCsquam 191 AEHDMKSVL NHL 192 LEIMTNLVTL BRCA 195 MEIKGTVTEF GBC 196 TELEVKIRDW BRCA, GBC, HNSCC, NSCLCadeno, NSCLCsquam, OSCAR, PACA, UBC 197 NEILTIHF BRCA, GC, HCC, NSCLCadeno, NSCLCsquam, OSCAR 198 REEEANWL CCC, HCC, NSCLCsquam, UBC 199 AELPENLKALF HNSCC 200 KELSVFKKF CLL, NHL 203 REILHAQTL CLL, NHL 204 YERPTLVEL AML, CLL 206 SEDPEKYYL CCC, NSCLCsquam 207 LEGGGRGGEF BRCA, OSCAR 208 SEFLLRIF BRCA 209 AEGEPPPAL UBC 210 AEGEPPPALAW NHL, UBC 211 LEMLDAHRL BRCA 213 DEDLFHKL OSCAR 215 SAMWIQLLY MEL 216 AGSPVMRKW NSCLCsquam 217 EVEVGDRTDW UEC 218 REAEEKEAQL CLL 219 WEVEVGDRTDW CLL, MEL, NHL, NSCLCadeno, RCC 221 KEAFGPQAL NSCLCsquam 223 SEVEGLAFV NSCLCadeno, PACA 225 VEAATVSKW BRCA, CCC, CRC, GBC, HNSCC, MEL, NSCLCadeno, OC, OSCAR, RCC, SCLC, UEC 227 ALTEDSIDDTF GBM 229 AEDLEKKYA CCC, CLL, MEL, PACA, UEC 230 AEALVDGKW UBC 231 AEALVDGKWQE UBC F 232 YEIRAEAL UBC 233 QEDKATQTL CLL 234 TEEPQRLFY BRCA, HCC, MEL, NSCLCadeno, OC, OSCAR, RCC 236 LEDQLKPMLEW MEL 237 QEIGQKTSV MEL 238 VEDDNYKLSL BRCA, CLL 239 DEDYTYLIL CCC 240 MELQVSSGF CLL 241 QELLDIANYL CCC, HCC 242 CDAQIQYSY AML 243 VEQINISQDW CRC, HNSCC 244 VESSQAFTW HNSCC 245 MEFQGPMPAGM NSCLCsquam 246 HEHGLFNLY MEL 247 KESMLKTTL HCC 248 KESQLPTVMDF HCC 249 YEMAIYKKY MEL, PRCA 251 DESADSEPHKY NHL 252 EEFIGKIGI AML, BRCA, CCC, CLL, CRC, GBC, GC, HCC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 253 QEILHGAVRF CCC, CRC, GBC, GBM, GC, HCC, HNSCC, NSCLCadeno, NSCLCsquam, OSCAR, PRCA, RCC, UBC 254 QEVAGYVLI NSCLCadeno 255 KQWEYNEKLAF GBM 256 RLLPGKWW PACA 258 IEVSSPITL CCC, HCC, NSCLCadeno 259 IEVSSPITLQAL CCC, NSCLCadeno, OC 260 VELMFPLLL BRCA 261 QEWDPQKTEKY CCC, UEC 262 YENILNAI GC 264 RELIKAIGL BRCA 265 EDNLIHKF GBC, HNSCC, OC, PACA 266 EEEDRDGHTW GBC, UBC 267 VELEVPQL GC, HCC 268 EDLAVHLY CLL 269 SEDLAVHL CLL 270 VLRPPGSSW UBC 271 REDLVGPEV CLL 272 SEQNIQRANLF CCC, HCC 273 TEFELLHQV GC 274 DEIDKLTGY GC, HCC, PRCA 275 GEQPPEGQW CLL 277 VEFPATRSL AML 278 DQVTVFLHF UBC 279 GEPVTQPGSLL CLL 280 AAEPLVGQRW RCC 281 HEIPQESL NSCLCsquam, OSCAR 282 KEFGIGDLVW AML, HNSCC, OSCAR 283 VEEEISRHY BRCA, CCC, CLL, CRC, GBC, HCC, HNSCC, MEL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC, UBC, UEC 284 SQYPHTHTF CLL 286 DELSVGRY CRC, OSCAR, PRCA 287 REVSVVDIL HCC 288 TEHFLKKFF HCC 289 NRYINIVAY GBM 290 AECILSKRL BRCA, HNSCC 291 DEQLLLRF CRC, OSCAR 292 HELALRQTV OSCAR 293 QEDEQLLLRF CRC, OSCAR 294 EEWEWIQKL GBM, HCC, PACA, UEC 295 QELEQEVISL CLL 296 AETIFIVRL OC 297 DEYLIPQQGFF GC, HCC, NSCLCadeno, NSCLCsquam, OSCAR 298 KEVASNSEL NSCLCsquam 299 AEVQIARKL CLL, CRC, GBC, HCC, MEL, NHL, NSCLCadeno, OC, OSCAR, RCC, UEC 300 KQTEATMTF CCC 301 AERIMFSDL OSCAR 302 EGEDAHLTQY NSCLCsquam 303 GEDAHLTQY HNSCC, NSCLCsquam 304 RELGFTEATGW CCC, CRC, GBC, MEL, NHL, NSCLCadeno, NSCLCsquam, OSCAR, RCC, UBC, UEC 305 AEKNRRDAETW HNSCC, NSCLCsquam, OSCAR, UBC 306 RRHPSFKRF GBC 307 YEQLLKWTW CRC, NHL, UBC, UEC 308 EEPKIDFRVY BRCA, CCC, CRC, HNSCC, MEL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC 309 SDDLRNVTW BRCA, NSCLCadeno 310 FELECPVKY CLL, NSCLCsquam 312 KEWEREKAVSL UBC 313 EEINQGGRKY CLL, CRC, NHL, NSCLCadeno, NSCLCother, NSCLCsquam 314 EMREERKF NSCLCadeno, NSCLCsquam 315 MEQQSQEY OSCAR 316 RLWPEPENW GBM 317 TEFQQIINL CLL 318 SESSSFLKV PACA 319 YEWEPFAEV NSCLCadeno 320 AENPLNIFY CCC, GBM, NHL, NSCLCsquam 321 AENPLNIFYI AML, NHL, NSCLCsquam 322 REESDWHYL BRCA 323 SETAWNVTY GBC, NSCLCadeno 324 QELSSIRQF NHL 325 AEQEIMKKV GBC 326 RELLDFSSW CRC, MEL, UBC, UEC 327 SEQHSLPVF NSCLCsquam 328 HENGVLTKF NSCLCadeno, NSCLCsquam 329 SEPQITVNF BRCA, GBC 330 SEHLFGTSY GC 331 KELEATKQYL NSCLCsquam, OSCAR 332 SEADWLRFW AML, BRCA, CCC, CLL, CRC, HCC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC, UBC, UEC 333 SEGTLPYSY GC, NSCLCsquam, OSCAR 334 LEWQNSSSM NHL 335 SETPTLQGL HCC 336 QEVNISLHY BRCA, CRC, HNSCC, NSCLCsquam, OSCAR 337 VEVIPEGAML CLL 338 AEMKFYWI NHL, OC 339 NEVKEIKGY OC 340 GELAPSHGL PRCA 341 HELESENKKW AML, NHL, NSCLCsquam, OSCAR 342 SENKKVWEF CLL, CRC, NHL, NSCLCsquam 343 SEFDLEQVW HNSCC, NHL, NSCLCsquam 344 DEIRVFGY HCC 345 AEYQAAILHL MEL 346 EEIENLQAQF MEL 347 LENPHVQSV AML 348 SEVLLTSISTF NSCLCadeno 349 LEWQHPSSW AML 350 EEMLENVSL CCC, HCC 351 EEGRVYVY GC, NSCLCsquam, OSCAR, PRCA 352 QEDELVKIRKY BRCA, CCC, CRC, HCC, MEL, NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC, SCLC, UEC 353 AETEEGIYW HNSCC 354 TEIMEKTTL CCC 355 SETSTGTSV NSCLCadeno, PACA 356 TEAVLNRY GC, NSCLCsquam, OSCAR 357 AELMDKPLTF CRC, NSCLCadeno 358 TEFHGGLHY BRCA, CRC, GC, HCC, HNSCC 359 NEFRRKLTF SCLC 360 DEMENLLTY BRCA, CLL, HCC, NHL, NSCLCsquam, OSCAR, PRCA, UEC 361 EDASLMGLY GBM 362 SEVEYINKY OC 363 EECDKAFHF BRCA, CCC, CLL, CRC, GC, HNSCC, NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, PRCA, UBC 364 EECDKAYSF BRCA, CCC, CLL, CRC, GC, HCC, HNSCC, NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC, UBC, UEC 365 NESGKAFNY BRCA, CCC, CLL, CRC, GBM, GC, HCC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC, UBC, UEC 366 EECGKAFKKF CLL 367 TEFAVKLKI NSCLCadeno 368 KEKVPGITI AML, MEL, NSCLCadeno, NSCLCsquam, OSCAR, PACA 369 KELEERMLHW HNSCC, MEL, NHL, NSCLCadeno 370 EEVLLANALW CLL, CRC, HCC, NHL, UBC 371 NEIGQELTGQEW BRCA, CCC, CRC, GBM, HCC, HNSCC, MEL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC 372 EEYKFPSLF BRCA, CLL, CRC, OC 373 REDPIVYEI MEL, NSCLCadeno, UBC 374 NEAEWQEIL CLL 375 HEATFGEKRF CCC, GBC, HNSCC, NSCLCsquam, OC, OSCAR, PACA, PRCA, UEC 378 QELFLQEVRM BRCA, CRC, HCC, HNSCC, MEL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PRCA 379 AENRVGKMEA CLL 380 EECGKAFRVF CLL, CRC, NHL 381 QELMAFSFAGL OSCAR 382 SELNPLALY HNSCC 383 EEMERDLDMY CLL, MEL, NHL, NSCLCsquam, UEC 384 LDGIPTAGW CLL, NHL 385 LEHPFLVNLW CLL, RCC 387 GEVQENYKL NSCLCsquam 388 VEIVTIPSL CLL, UEC 389 DEQRRQNVAY CRC, MEL, OSCAR 390 GEYNKHAQLW OC 391 TESIGAQIY OC 392 TEVSVLLLTF OC 393 SETILAVGL BRCA, CLL, HCC, NSCLCsquam 394 SEILRVTLY AML, CRC, HCC, NSCLCadeno, NSCLCsquam, OC, PACA 395 AEDFVWAQW CLL, CRC, HCC, NHL, NSCLCsquam 396 MELLFLDTF CLL, NHL 397 EECGKAFSVF CLL 398 AEIIRYIF AML 399 IEQADWPEI NSCLCadeno 400 TELGLFGVW HNSCC, NSCLCadeno 401 VENIFHNF BRCA, GC, HCC, MEL, NSCLCadeno, NSCLCsquam, OSCAR 402 IETSSEYFNF BRCA, CRC, HNSCC, NHL, NSCLCadeno, NSCLCsquam, OSCAR, PACA, UBC, UEC 403 QESVHVASY AML, BRCA, CLL, GBM, NHL, PACA, UEC 404 AEREQVIKL AML 405 YEHAFNSIVW RCC 407 MEFQNTQSY BRCA, CLL, GC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCsquam, OSCAR 408 AFSLLSAAFY NSCLCsquam 409 QEAKPRATW BRCA, CCC, CLL, CRC, GBC, GC, HCC, NHL, NSCLCadeno, NSCLCsquam, PRCA, UBC 410 RELEEEFYSL CLL 411 AERDLNVTI NSCLCadeno, PACA 412 EESFDSKFY CLL, CRC, HNSCC, NHL, NSCLCadeno, NSCLCsquam, PACA 414 AEGYLDLDGI NSCLCadeno 415 EEAGFPLAY HNSCC 416 DELMRKESQW CLL, CRC, MEL, NHL, NSCLCsquam, UBC, UEC 417 EESFRCLPEW NHL 418 GEPRKLLTQDW HNSCC, NSCLCadeno 419 SELSLLSLY PRCA 420 MEVDPIGHVY NSCLCsquam 421 TEDYSKQAL CCC, NSCLCsquam, UBC 422 EEAQWWRKYF CLL, CRC, NHL, UBC 423 KEAINLLKNY BRCA, CLL, HNSCC, NHL 424 EEHVYESIIRW CLL, CRC, NHL 425 KEVDPASNTY OSCAR 426 AESLFREAL HNSCC, NSCLCsquam 427 AEMLGSVVGNW NSCLCadeno 429 RETEDYSKQAL CCC, NSCLCsquam 430 RELARWTL SCLC 431 QELLDFTNW SCLC 432 TEENGFWYL BRCA 433 AEEGPSVPKIY CLL, NHL 434 AEQQQQQMY NHL 435 FETEQALRL NSCLCadeno, NSCLCsquam, PACA, UBC 436 AEADLSYTWDF MEL 437 HEDPSGSLHL BRCA, UBC 438 AELDSKILAL BRCA, NSCLCsquam, OC 439 VEVGDRTDW NHL 440 QEVAQVASA HNSCC 441 QEVAQVASAIL CCC, NSCLCsquam, UBC 442 KESDAGKYY CLL 443 EEYAGQITL CLL 444 SESALQTVI CCC, NSCLCadeno, UBC 445 QEVGEITNL CCC, NSCLCsquam, UBC 446 AENIKKFLY CRC, HCC, MEL, NSCLCsquam, PRCA, RCC 447 KEFGLDSVEL CCC, HCC 448 ALSPVPSHW CLL, NHL 449 RENDFEPKF NHL 450 REIENGNSF AML, CRC, GBC, HNSCC, NSCLCadeno, NSCLCsquam, PACA 452 NEVDGEYRY BRCA, CCC, CRC, GBC, GC, HCC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA, PRCA, RCC, UBC, UEC 453 SESKVFQLL BRCA, CCC, CRC, HCC, HNSCC, NHL, NSCLCadeno, NSCLCsquam, OSCAR, PACA 454 SESSSAFQF MEL, NHL 455 QESVHVASYYW CLL, UBC, UEC 456 SESPIRISV NSCLCsquam, OSCAR, PACA

    Example 2

    [0353] Expression Profiling of Genes Encoding the Peptides of the Invention

    [0354] 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.

    [0355] RNA Sources and Preparation

    [0356] 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's protocol.

    [0357] Total RNA from healthy human tissues for RNASeq experiments was obtained from: Asterand (Detroit, Mich., USA & 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 & 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).

    [0358] 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).

    [0359] RNAseq Experiments

    [0360] 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'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'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.

    [0361] 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. 2A-2U. Expression scores for further exemplary genes are shown in Table 9.

    TABLE-US-00011 TABLE 9 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&neck, kidney, large intestine, liver, lung, lymph node, nerve, parathyroid, pancreas, pituitary, skeletal muscle, skin, small intestine, spleen, stomach, thyroid gland, trachea, 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. Gene Expression in tumor samples very highly Seq ID over-expressed highly over-expressed over-expressed No Sequence (+) (++) (+++) 1 KEVDPASNTYTL BRCA, CRC, GC, HCC, NSCLCadeno GBC, HNSCC, UEC MEL, NSCLCsquam, OC, OSCAR, SCLC, UBC 2 EEFLRPRSL CLL PRCA 3 DEIFTNDRRW UEC GBM, MEL, SCLC PRCA 4 AEALGAAKKL GBC, NSCLCadeno, OC UEC OSCAR 5 VEFLLLKY BRCA, GBC, HCC, MEL NSCLCadeno, NSCLCsquam, SCLC 6 AELVGPVIPQDW PRCA 7 SESDLVNFI GBM, MEL PRCA 8 ELMEVDPIGHLY CRC, NHL, OC, GBC, NSCLCadeno, GC, HCC, PACA UEC HNSCC, MEL, NSCLCsquam, OSCAR, SCLC, UBC 9 MEVDPIGHLYIF CRC, NHL, OC, GBC, NSCLCadeno, GC, HCC, PACA UEC HNSCC, MEL, NSCLCsquam, OSCAR, SCLC, UBC 10 SEYPTKNYV HCC, HNSCC, CCC, GC, GBC, NSCLCsquam, NSCLCadeno NSCLCother, OSCAR, PACA, UEC OC 11 EENIVAIGI MEL GBM PRCA 12 KEVDPTGHSF HCC, UEC GBC, GC, HNSCC, MEL, UBC NSCLCadeno, NSCLCsquam, OC, OSCAR, SCLC 13 VEAQDRETW NSCLCadeno, RCC NSCLCsquam, SCLC 14 EMPGGPVW HCC, RCC CCC, GBC, GC, MEL, CRC, HNSCC, NHL, NSCLCadeno, NSCLCother, OC, OSCAR, PACA, NSCLCsquam, UBC, UEC SCLC 15 MEAELVRRI GC, HNSCC, HCC, MEL, SCLC GBC NSCLCsquam, OC, UBC 16 NESDRLVYF GBC, GBM, MEL, OC, CLL NHL UBC 17 SEIYQPRGF GBC, GBM, MEL, OC, CLL NHL UBC 18 QEAPRPASSL HCC, MEL, CRC, GBC, GC, BRCA, CCC, NSCLCother, RCC, HNSCC, PACA SCLC NSCLCadeno, NSCLCsquam, OC, OSCAR, UBC, UEC 19 MEHSDENIQFW PACA NHL 20 LEALLSDLF PRCA 21 SEAKEIKSQL BRCA 22 TEEITEGVW AML 23 REYNLHRVA CRC, GC, MEL, HNSCC, NSCLCadeno, PACA NSCLCsquam, OSCAR, UBC 24 EELALRIGL NSCLCother GBM,SCLC 25 SEKEPGQQY GBC HCC 26 EESSSPVDEY BRCA, GBC, SCLC HCC, MEL 27 GETCVRITY MEL 28 QEFPAHSL NHL CLL 29 TENPKKFKI HCC, OC CCC, NSCLCadeno 30 EEFCFSVRF AML 31 MESAKETRY BRCA, OC, UEC 32 REYEYDLKW AML 33 IEYENQKRL AML 34 AEPPILYSEY BRCA, OC, UEC 35 RELVHMINW BRCA, OC, UEC 36 LEQASRIWSW MEL 37 IEQGRVVLW HCC, OSCAR, UBC GBC, SCLC 38 DEVRFFKGNKY CRC, GC, HNSCC, NSCLCadeno, PACA, NSCLCsquam, UBC OSCAR 39 AEAMGKFKQCF OC, UEC 40 REVDPDDSYVF SCLC HCC, MEL 41 EENTGKTYF CRC, GC, HNSCC, NSCLCadeno, PACA, NSCLCsquam, UBC OSCAR 42 SEENTGKTYF CRC, GC, HNSCC, NSCLCadeno, PACA, NSCLCsquam, UBC OSCAR 43 SEKIVYVY GBC, OC, SCLC, HCC, MEL, NHL UBC 44 SEFGAPRW HCC, PRCA 45 EEINELNRMI HNSCC, BRCA, GBC, MEL, NSCLCother, NSCLCadeno, OC, NSCLCsquam, PACA, UBC SCLC 46 SELGLPKEV NSCLCadeno, UBC HNSCC, NSCLCsquam, OSCAR 47 TEVHSSPAQRW AML, CCC, GC, HCC, UBC NHL, OC, PACA, UEC 48 DEVRALIF MEL AML 49 SEYVHSSF CRC, NSCLCsquam, BRCA, CCC, GBC, OC, UBC, UEC GC, HNSCC, NSCLCadeno, OSCAR, PACA 50 SEYVHSSFSGF CRC, NSCLCsquam, BRCA, CCC, GBC, OC, UBC, UEC GC, HNSCC, NSCLCadeno, OSCAR, PACA 51 VEMTGKHQL AML 52 EDNPSGHTY BRCA, MEL, GBC, HCC, NHL NSCLCadeno, NSCLCsquam, OC, SCLC 53 KEDNPSGHTY BRCA, MEL, GBC, HCC, NHL NSCLCadeno, NSCLCsquam, OC, SCLC 54 QEISAHRTEF NHL CLL 55 TEFHMQFSY NHL CLL 56 ALEEGGGYIF BRCA, GBC, GBM, CRC, OC GC, HNSCC, MEL, NSCLCadeno, NSCLCother, OSCAR, PACA, UBC, UEC 57 SEATHIITI AML 58 KEMDPSRQSY HCC 59 AEIEADRSYQ GBC, GC, CCC, HNSCC, NSCLCadeno, NSCLCsquam, NSCLCother, PACA OSCAR, UBC 60 EEAVRSVAF CLL NHL 61 AEYSVHKI GBC, GC, CCC, HNSCC, NSCLCadeno, NSCLCsquam, NSCLCother, PACA, OSCAR, UBC UEC 62 AEYSVHKITSTF GBC, GC, CCC, HNSCC, NSCLCadeno, NSCLCsquam, NSCLCother, PACA, OSCAR, UBC UEC 63 YEQVLFGF UEC PRCA 64 EEYQDSFERY GBC, MEL, SCLC HNSCC, NSCLCsquam, OSCAR 65 SESMVESKF MEL 66 AEVTLNNTI NHL CLL 67 TEGAVEVKY CCC MEL 68 NEIDIHSIYF NSCLCother, OSCAR HNSCC 69 DENIQKFIW NSCLCother, OSCAR HNSCC 70 AEAEEAMKRL CCC, GC, HNSCC, NSCLCadeno, NSCLCsquam, NSCLCother, PACA, OSCAR UBC 71 AEVGDIIKV CCC HCC 72 AEVGDIIKVHF CCC HCC 73 GEGTLRLSW MEL 74 AELEGALQKA BRCA, GBC, MEL, NSCLCadeno, UBC NSCLCsquam, OC, SCLC 75 LETSCGSSTAY MEL 76 RLNEHPSNNW GC, NSCLCadeno, CCC, HNSCC, NSCLCother, PACA, NSCLCsquam, UBC OSCAR 77 QETLAESTW AML, HNSCC, HCC, NHL NSCLCsquam 78 TEFSNHINL HCC, OC, SCLC, BRCA, PRCA UEC 79 TEAQRLDCW MEL 80 TEQSLYYRQW BRCA, HCC, MEL, PRCA OC, SCLC, UEC 81 GEKATMQNL NSCLCsquam, UBC HNSCC, OSCAR 82 AVFDESKSW CCC HCC 83 TEGGTQKTF CCC HCC 84 AETSYVKVLEY BRCA, CCC, OC, GBC, GC, HNSCC, HCC, MEL, UBC NHL, NSCLCadeno, NSCLCsquam, SCLC OSCAR 85 SEIDEKVTDL HCC, NSCLCadeno GBC, GC, HNSCC, MEL, UBC NSCLCsquam, OC, OSCAR, SCLC 86 QTLKAMVQAW AML, BRCA, GC, GBC, HNSCC, MEL, OC, HCC, NHL, OSCAR, NSCLCadeno, SCLC, UEC UBC NSCLCsquam, RCC 87 GEARGDQVDW CCC, GBC, GBM, GC, HNSCC, HCC, MEL, NHL, OC, PACA NSCLCadeno, SCLC NSCLCsquam, OSCAR, UBC 88 KEFTVSGNIL GC, HNSCC, NHL, HCC, OC, UBC GBC, MEL, NSCLCadeno, SCLC NSCLCsquam, UEC 89 KEFYPVKEF OC BRCA 90 EESLLSSW GC, NSCLCadeno, HCC, HNSCC, MEL, GBC, SCLC NHL, NSCLCother, NSCLCsquam OSCAR, PACA 91 EESLLSSWDF GC, NSCLCadeno, HCC, HNSCC, MEL, GBC, SCLC NHL, NSCLCother, NSCLCsquam OSCAR, PACA 92 KEPSQSCIAQY GBM, NSCLCadeno, HNSCC, OSCAR NSCLCsquam, OC, RCC, UBC, UEC 93 SEAGLTANQY CRC, GBM, MEL, HCC, NHL NSCLCadeno, RCC, SCLC 94 SLAELIAKDW CRC, GBM, MEL, HCC, NHL NSCLCadeno, RCC, SCLC 95 AAFEDAQGHIW HCC, OC, RCC, BRCA, CCC, CRC, SCLC GBC, GC, HNSCC, NSCLCadeno, NSCLCsquam, OSCAR, PACA, UBC, UEC 96 MDELEEGESY GBM,SCLC 97 ELVHMINW BRCA, OC, UEC 98 SEESAGPLL BRCA UEC 99 SECVKSLSF UEC BRCA, PRCA 100 QGDVVDYSFY HCC, OSCAR, UBC GBC, SCLC 101 SEENTGKTY CRC, GC, HNSCC, NSCLCadeno, PACA, NSCLCsquam, UBC OSCAR 102 TELADLDAAW AML, CCC, HNSCC, BRCA, GBC, HCC, NHL, NSCLCother, MEL, NSCLCadeno, NSCLCsquam, OC, SCLC OSCAR, PACA, UBC, UEC 103 AELFLTKSF NSCLCadeno, UBC HNSCC, NSCLCsquam, OSCAR 104 EVHSSPAQRW AML, CCC, GC, HCC, UBC NHL, OC, PACA, UEC 105 EEIFKTLNY AML 106 SVISDSPRSW NHL CLL 107 YQENPRAAW SCLC GBM,RCC 108 QETNKVETY CCC, NSCLCother, HNSCC, UBC NSCLCsquam, OSCAR, RCC 109 AFSPAAGNTW GBM 110 EVEVGEVKSW SCLC HCC 111 QEIDQKRLEF AML, BRCA, GBC, OC, SCLC HCC, MEL, NSCLCadeno 112 AEIEADRSYQH GBC, GC, CCC, HNSCC, NSCLCadeno, NSCLCsquam, NSCLCother, PACA OSCAR, UBC 113 MEFKTLNKN GBM RCC 114 VEVNGVPRW CCC, OSCAR MEL 115 QEPFTRPVL NHL CLL 116 AEANPRDLGASW GBC, HNSCC, MEL, HCC NSCLCadeno, SCLC 117 SEVPVDSHY CCC MEL 118 SEVPVDSHYY CCC MEL 119 VEVKYEGHW CCC MEL 120 VTEGAVEVKY CCC MEL 121 YENIPVDKV CRC, GBC, NHL, BRCA, GC, HNSCC, UBC, UEC MEL, NSCLCadeno, NSCLCsquam, OC, OSCAR, PACA 122 GESVSWHLF NSCLCother, OSCAR HNSCC 123 DEINHQSL AML, BRCA, CCC, CLL, SCLC CRC, GBC, GBM, GC, HCC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCother, NSCLCsquam, OC, OSCAR, PACA, UBC, UEC 124 NENLDYAIL AML, BRCA, CCC, CLL, SCLC CRC, GBC, GBM, GC, HCC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCother, NSCLCsquam, OC, OSCAR, PACA, UBC, UEC 125 LEVLHQGQW CCC MEL 126 SEASQSPQY UEC 127 RYFDENIQKFIW NSCLCother, OSCAR HNSCC 128 TELTEARVQVW MEL 129 EEAMKRLSY CCC, GC, HNSCC, NSCLCadeno, NSCLCsquam, NSCLCother, PACA, OSCAR UBC 130 REYQEVMNSKL BRCA, GBC, MEL, NSCLCadeno, UBC NSCLCsquam, OC, SCLC 131 RESHLTEIRQY BRCA, HCC, OC, PRCA SCLC, UEC 132 AESFTSGRHYW BRCA, CCC, GBC, HNSCC, OSCAR, GBM, MEL, PACA NSCLCsquam, OC, RCC, UBC 133 IEAPKLMVV MEL 134 IEIKDRLQL CLL, NHL 135 QEIDRGQYI MEL 136 EEMPEEIHL NSCLCother, HNSCC, OSCAR NSCLCsquam 137 EKGLISAF BRCA, CRC, GBC, SCLC GC, HNSCC, MEL, NSCLCadeno, NSCLCsquam, OC, OSCAR, UBC 138 KEAPNIVTL HCC, OC, UEC BRCA, PRCA 139 AESDFSNNML MEL 140 TEHSGIYSC NHL CLL 141 SEKWFRMGF AML 142 QELFLHPVL CLL, NHL 143 HEHIRSHW HCC 144 IEAYLERIGY BRCA 145 EELRMLSF CLL, NHL 146 MEELRMLSF CLL, NHL 147 RMLSFQQMTW CLL, NHL 148 KESDAGRYY CLL, NHL 149 AETEPERHLG PRCA 150 SEVFHVSEA GBM 151 TELQIPSF GBM 152 HENLIEDF CCC HCC 153 IEIILLSGSL BRCA, HCC, MEL, GBC, OC, SCLC NSCLCadeno, UBC 154 NEAGEMIKHY NSCLCadeno MEL 155 TEDARHPESW NHL 156 DAIPPPTLTW MEL 157 SQDVAGTTF MEL 158 VEEERYTGQW AML UBC 159 EEVQDGKVI NSCLCsquam, UBC HNSCC, OSCAR 160 AEIATTGQLY GBM 161 GESSEVKAVL AML 162 EAYDIELNKW NHL CLL 163 AEDEDGKIVGY GBC, MEL HCC 164 DEDGKIVGY GBC, MEL HCC 165 EEIEAHIAL GBM,SCLC AML 166 EEQDFINNRY GBM 167 AETENRYCV NSCLCsquam, UBC HNSCC, OSCAR 168 EEGPSVPKIY AML, CLL NHL, PRCA 169 KEHNSSVPWSS NHL, NSCLCsquam, HNSCC, MEL OC, OSCAR, SCLC 170 REMFVFKDQW BRCA GBM, MEL 171 WEVVHTVF MEL 172 RENPGMFSW MEL 173 SEHSLEGQKF GBM 174 DENDAGNLITF GC, HNSCC, MEL, CRC, GBC, NSCLCother, NSCLCadeno NSCLCsquam, OC, OSCAR, PACA, UBC 175 NLKSPIPLW GC, HNSCC, MEL, CRC, GBC, NSCLCother, NSCLCadeno NSCLCsquam, OC, OSCAR, PACA, UBC 176 GETQQHIQL MEL 177 LEEPMPFFY MEL, NSCLCadeno, GBC, HNSCC NSCLCother, NSCLCsquam, OC, OSCAR, UBC 178 MEGAALLKIF NSCLCsquam, UBC PRCA, UEC 179 EEHIFSAF NSCLCsquam NHL 180 EEHSSKLQTSL PRCA 181 HEVAQDDHL PRCA 182 EELHAALSEW CCC, GBC, GC CRC 183 KEMQVTISQQL CCC, GC PACA 184 EEQLLQKVM AML 185 TEANVQALF AML CLL, NHL 186 EEIFAHLGL AML 187 TEQALRLSV NSCLCsquam, UBC HNSCC, OSCAR 188 AEFVPKADLL MEL 189 ALNGDIYVW NHL 190 NEAGEVSKHF MEL 191 AEHDMKSVL NHL CLL 192 LEIMTNLVTL PRCA BRCA 193 RELRPLFDRQW NHL CLL 194 TEGDVLNYIF NHL CLL 195 MEIKGTVTEF CCC, GC, BRCA, PRCA NSCLCsquam 196 TELEVKIRDW NSCLCsquam, UBC HNSCC, OSCAR 197 NEILTIHF CCC HCC 198 REEEANVVL GBC, OC, OSCAR, CCC PACA, UBC 199 AELPENLKALF MEL, NSCLCsquam HNSCC, OSCAR 200 KELSVFKKF NHL CLL 201 MEILWKTLT CLL 202 RELPLVLLA SCLC 203 REILHAQTL CLL 204 YERPTLVEL AML, CLL, NHL PRCA 205 MEIEGAGNFL BRCA, CRC, GC, CCC, GBC HNSCC, MEL, NSCLCadeno, NSCLCother, NSCLCsquam, OSCAR, PACA, SCLC, UBC 206 SEDPEKYYL BRCA, CRC, GC, CCC, GBC HNSCC, MEL, NSCLCadeno, NSCLCother, NSCLCsquam, OSCAR, PACA, SCLC, UBC 207 LEGGGRGGEF MEL NHL 208 SEFLLRIF GC UEC 209 AEGEPPPAL HCC, MEL, NHL, OC, UBC PACA, UEC 210 AEGEPPPALAW HCC, MEL, NHL, OC, UBC PACA, UEC 211 LEMLDAHRL OC BRCA, UEC 212 SEASVYLFRF HCC, MEL, NHL, OC, UBC PACA, UEC 213 DEDLFHKL GC, HNSCC, CRC OSCAR, UBC 214 SVNPIIYGF GBC HCC 215 SAMWIQLLY MEL 216 AGSPVMRKW RCC 217 EVEVGDRTDW NHL 218 REAEEKEAQL CLL 219 WEVEVGDRTDW NHL 220 EEEVFSGMKL GBM 221 KEAFGPQAL GBM 222 SEDTIHTHL GBM 223 SEVEGLAFV GBM 224 TETDIDREY GBM 225 VEAATVSKW GBM 226 AEDNMVTSY BRCA 227 ALTEDSIDDTF GBM 228 LEYEAPKLY AML 229 AEDLEKKYA GC UEC 230 AEALVDGKW UBC 231 AEALVDGKWQEF UBC 232 YEIRAEAL UBC 233 QEDKATQTL AML, NHL CLL 234 TEEPQRLFY AML, NHL CLL 235 SESLPRAPL GBM, OC SCLC 236 LEDQLKPMLEW AML 237 QEIGQKTSV NSCLCother, NSCLCadeno NSCLCsquam 238 VEDDNYKLSL CLL 239 DEDYTYLIL HCC 240 MELQVSSGF NHL CLL 241 QELLDIANYL HCC 242 CDAQIQYSY NSCLCsquam HNSCC, OSCAR 243 VEQINISQDW GC, HNSCC, CRC NSCLCsquam, OSCAR, UBC 244 VESSQAFTW NSCLCsquam HNSCC, OSCAR 245 MEFQGPMPAGM CCC, GBC, GC, OSCAR HNSCC, NSCLCadeno, NSCLCother, NSCLCsquam, PACA, UBC 246 HEHGLFNLY BRCA, MEL, OC PRCA 247 KESMLKTTL HCC 248 KESQLPTVMDF HCC 249 YEMAIYKKY BRCA, MEL, OC PRCA 250 AELDHLASL NSCLCother 251 DESADSEPHKY NHL 252 EEFIGKIGI NHL 253 QEILHGAVRF GBM 254 QEVAGYVLI GBM 255 KQWEYNEKLAF AML 256 RLLPGKVVW UEC 257 HAIDGTNNW MEL, NSCLCsquam, OC, UEC RCC, SCLC 258 IEVSSPITL HCC 259 IEVSSPITLQAL HCC 260 VELMFPLLL PRCA 261 QEWDPQKTEKY UEC 262 YENILNAI CCC, GBC, GC, OSCAR HNSCC, NSCLCother, NSCLCsquam, PACA, UBC 263 AEQLRGFNA CCC, GC, HNSCC, OSCAR NSCLCadeno, NSCLCsquam, PACA, UBC 264 RELIKAIGL BRCA UEC 265 EDNLIHKF BRCA, CCC, NHL, GBC NSCLCsquam, OC, OSCAR, SCLC, UBC, UEC 266 EEEDRDGHTW BRCA, CCC, NHL, GBC NSCLCsquam, OC, OSCAR, SCLC, UBC, UEC 267 VELEVPQL HCC 268 EDLAVHLY NHL CLL 269 SEDLAVHL NHL CLL 270 VLRPPGSSW NSCLCsquam, HNSCC OSCAR 271 REDLVGPEV NHL CLL 272 SEQNIQRANLF HCC 273 TEFELLHQV GBC, GC CRC 274 DEIDKLTGY PRCA 275 GEQPPEGQW AML, NHL CLL 276 SEYQDGKEF AML 277 VEFPATRSL AML 278 DQVTVFLHF PRCA 279 GEPVTQPGSLL AML, NHL CLL 280 AAEPLVGQRW CLL 281 HEIPQESL MEL BRCA 282 KEFGIGDLVW AML 283 VEEEISRHY BRCA 284 SQYPHTHTF CLL 285 AEHPDFSPCSF UEC AML 286 DELSVGRY UEC AML 287 REVSWDIL HCC 288 TEHFLKKFF HCC 289 NRYINIVAY GBM 290 AECILSKRL AML, BRCA, GBC, SCLC GBM, HNSCC, MEL, NSCLCother, NSCLCsquam, OC, OSCAR, UEC 291 DEQLLLRF GC, HNSCC, CRC NSCLCsquam, OSCAR, UBC 292 HELALRQTV HNSCC 293 QEDEQLLLRF GC, HNSCC, CRC NSCLCsquam, OSCAR, UBC 294 EEWEWIQKL GBM HCC 295 QELEQEVISL AML, NHL, PRCA CLL 296 AETIFIVRL OC NHL 297 DEYLIPQQGFF GBM 298 KEVASNSEL OSCAR HNSCC 299 AEVQIARKL AML, NHL CLL 300 KQTEATMTF HCC 301 AERIMFSDL BRCA PRCA 302 EGEDAHLTQY NSCLCsquam, UBC HNSCC, OSCAR 303 GEDAHLTQY NSCLCsquam, UBC HNSCC, OSCAR 304 RELGFTEATGW MEL 305 AEKNRRDAETW HNSCC 306 RRHPSFKRF CCC, GC, PACA CRC 307 YEQLLKVVTW GBC, OC, UEC NHL 308 EEPKIDFRVY BRCA 309 SDDLRNVTW BRCA 310 FELECPVKY NHL CLL 311 REKDLPNYNW NSCLCother 312 KEWEREKAVSL UBC 313 EEINQGGRKY CLL, NHL CRC 314 EMREERKF CLL, NHL CRC 315 MEQQSQEY OSCAR HNSCC 316 RLWPEPENW UBC GBM 317 TEFQQIINL CLL, NHL CRC 318 SESSSFLKV BRCA, CCC, CRC, NSCLCadeno GBC, GBM, GC, HNSCC, MEL, NSCLCother, NSCLCsquam, OSCAR, PACA, SCLC, UBC, UEC 319 YEWEPFAEV BRCA 320 AENPLNIFY GBM 321 AENPLNIFYI GBM 322 REESDWHYL BRCA, MEL, OC PRCA 323 SETAWNVTY GC, HCC, HNSCC, GBC MEL, NHL, NSCLCadeno, NSCLCsquam, OC, OSCAR, SCLC 324 QELSSIRQF NHL, OC 325 AEQEIMKKV GBC, HCC, HNSCC, MEL, NSCLCsquam 326 RELLDFSSW CRC 327 SEQHSLPVF NSCLCadeno, NSCLCother, NSCLCsquam 328 HENGVLTKF NSCLCadeno, NSCLCother, NSCLCsquam 329 SEPQITVNF MEL, NSCLCadeno, NSCLCsquam, OSCAR 330 SEHLFGTSY CCC, GBC, MEL, OC, RCC, SCLC, UEC 331 KELEATKQYL BRCA, CCC, CRC, GBC, GBM, GC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCsquam, OSCAR, PACA, SCLC, UBC, UEC 332 SEADWLRFW BRCA 333 SEGTLPYSY GBM 334 LEWQNSSSM CCC, GC, HNSCC, NHL, NSCLCadeno, NSCLCsquam, OSCAR, PACA 335 SETPTLQGL PRCA 336 QEVNISLHY AML, CCC, PACA, UEC 337 VEVIPEGAML SCLC 338 AEMKFYVVI NHL, OC 339 NEVKEIKGY UEC 340 GELAPSHGL PRCA 341 HELESENKKW NHL 342 SENKKWVEF NHL 343 SEFDLEQVW BRCA, CCC, GBC, GC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCsquam, OSCAR, PACA, UBC, UEC 344 DEIRVFGY HCC 345 AEYQAAILHL MEL 346 EEIENLQAQF MEL 347 LENPHVQSV CCC, NSCLCadeno, NSCLCsquam, OC, SCLC 348 SEVLLTSISTF CCC, GBC, NSCLCadeno, RCC 349 LEWQHPSSW AML 350 EEMLENVSL HCC 351 EEGRVYVY AML, GC, NSCLCother 352 QEDELVKIRKY MEL 353 AETEEGIYW HNSCC, NSCLCsquam, OSCAR 354 TEIMEKTTL MEL, NSCLCsquam, OC, SCLC, UEC 355 SETSTGTSV BRCA, CCC, CRC, GBC, GC, HNSCC, MEL, NSCLCadeno, NSCLCsquam, OSCAR, PACA, SCLC, UBC, UEC 356 TEAVLNRY BRCA, CCC, CRC, GBC, GC, HNSCC, MEL, NSCLCadeno, NSCLCsquam, OSCAR, PACA, SCLC, UBC, UEC 357 AELMDKPLTF BRCA, NHL, SCLC 358 TEFHGGLHY GBC, GC, PACA 359 NEFRRKLTF AML 360 DEMENLLTY BRCA, PRCA 361 EDASLMGLY SCLC 362 SEVEYINKY MEL 363 EECDKAFHF PRCA 364 EECDKAYSF PRCA 365 NESGKAFNY PRCA 366 EECGKAFKKF CLL 367 TEFAVKLKI CCC, GBC, RCC 368 KEKVPGITI SCLC 369 KELEERMLHW CCC, NHL, NSCLCadeno, PACA 370 EEVLLANALW BRCA 371 NEIGQELTGQEW RCC 372 EEYKFPSLF SCLC 373 REDPIVYEI CCC, GBC, RCC 374 NEAEWQEIL CLL 375 HEATFGEKRF HNSCC, NSCLCsquam 376 SESDGIEQL HNSCC, NSCLCsquam 377 AEDARGWTA OC, UBC 378 QELFLQEVRM CLL 379 AENRVGKMEA GBM 380 EECGKAFRVF CLL 381 QELMAFSFAGL SCLC 382 SELNPLALY BRCA, HNSCC, OC, OSCAR, UBC 383 EEMERDLDMY CLL 384 LDGIPTAGW CLL 385 LEHPFLVNLW MEL 386 EESDYITHY BRCA, OC, PRCA 387 GEVQENYKL PRCA 388 VEIVTIPSL CLL 389 DEQRRQNVAY OC, PACA, SCLC 390 GEYNKHAQLW UEC 391 TESIGAQIY UEC 392 TEVSVLLLTF UEC 393 SETILAVGL NSCLCother, SCLC 394 SEILRVTLY AML 395 AEDFVWAQW CLL 396 MELLFLDTF BRCA, CLL, MEL, OC 397 EECGKAFSVF CLL 398 AEIIRYIF AML 399 IEQADWPEI AML 400 TELGLFGVW GBM, MEL, RCC 401 VENIFHNF MEL, NSCLCadeno 402 IETSSEYFNF OC 403 QESVHVASY AML 404 AEREQVIKL HNSCC, OC, OSCAR, UBC 405 YEHAFNSIVW HNSCC, OC, OSCAR, UBC 406 GETVVLKNM GBM 407 MEFQNTQSY MEL 408 AFSLLSAAFY BRCA 409 QEAKPRATW HNSCC, OC 410 RELEEEFYSL CLL 411 AERDLNVTI CRC, GC, NSCLCadeno, PACA 412 EESFDSKFY SCLC 413 TELEPGLTY GBM 414 AEGYLDLDGI HCC, NSCLCadeno 415 EEAGFPLAY PRCA 416 DELMRKESQW SCLC 417 EESFRCLPEW BRCA, CLL 418 GEPRKLLTQDW CRC, PACA BRCA, GC, HCC, GBC, HNSCC, NHL, NSCLCadeno, MEL, UEC NSCLCsquam, OC, OSCAR, SCLC, UBC 419 SELSLLSLY PRCA 420 MEVDPIGHVY CCC, CRC, NHL, GBC, NSCLCadeno, GC, HCC, PACA UEC HNSCC, MEL, NSCLCsquam, OSCAR, SCLC, UBC 421 TEDYSKQAL CCC, GC, HNSCC, NSCLCadeno, NSCLCsquam, NSCLCother, PACA, OSCAR, UBC UEC 422 EEAQWWRKYF AML, BRCA, CCC, CLL, SCLC CRC, GBC, GBM, GC, HCC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCother, NSCLCsquam, OC, OSCAR, PACA, UBC, UEC 423 KEAINLLKNY AML, BRCA, CCC, CLL, SCLC CRC, GBC, GBM, GC, HCC, HNSCC, MEL, NHL, NSCLCadeno, NSCLCother, NSCLCsquam, OC, OSCAR, PACA, UBC, UEC 424 EEHVYESIIRW AML CLL, NHL 425 KEVDPASNTY BRCA, CRC, GC, HCC, NSCLCadeno GBC, HNSCC, UEC MEL, NSCLCsquam, OC, OSCAR, SCLC, UBC 426 AESLFREAL BRCA, CRC, GC, HCC, NSCLCadeno GBC, HNSCC, UEC MEL, NSCLCsquam, OC, OSCAR, SCLC, UBC 427 AEMLGSVVGNW CCC, CRC, NHL, OC, GBC, NSCLCadeno, GC, HCC, PACA UEC HNSCC, MEL, NSCLCsquam, OSCAR, SCLC, UBC 428 AEEKAAVTSL AML, HNSCC, NHL, GBC, HCC, MEL NSCLCadeno, NSCLCother, OSCAR, PACA 429 RETEDYSKQAL CCC, GC, HNSCC, NSCLCadeno, NSCLCsquam, NSCLCother, PACA, OSCAR, UBC UEC 430 RELARVVTL GBC, NSCLCadeno, NSCLCother, SCLC NSCLCsquam, UEC 431 QELLDFTNW SCLC 432 TEENGFWYL BRCA 433 AEEGPSVPKIY AML, CLL NHL, PRCA 434 AEQQQQQMY NHL 435 FETEQALRL NSCLCsquam, UBC HNSCC, OSCAR 436 AEADLSYTWDF MEL 437 HEDPSGSLHL BRCA UBC 438 AELDSKILAL BRCA 439 VEVGDRTDW NHL 440 QEVAQVASA CCC, GBC, GC, OSCAR HNSCC, NSCLCadeno, NSCLCsquam, PACA, UBC 441 QEVAQVASAIL CCC, GBC, GC, OSCAR HNSCC, NSCLCadeno, NSCLCsquam, PACA, UBC 442 KESDAGKYY NHL CLL 443 EEYAGQITL NHL CLL 444 SESALQTVI CCC, GC, HNSCC, OSCAR NSCLCother, NSCLCsquam, PACA, UBC 445 QEVGEITNL CCC, GC, HNSCC, OSCAR NSCLCadeno, NSCLCother, NSCLCsquam, PACA, UBC 446 AENIKKFLY PRCA 447 KEFGLDSVEL PRCA 448 ALSPVPSHW CLL NHL 449 RENDFEPKF CLL, NHL CRC 450 REIENGNSF CRC, GC, NSCLCadeno, PACA, RCC 451 REYEDGPLSL NSCLCsquam, SCLC, UBC 452 NEVDGEYRY NHL 453 SESKVFQLL CCC, NSCLCadeno, PACA 454 SESSSAFQF MEL 455 QESVHVASYYW AML 456 SESPIRISV HNSCC

    Example 3

    [0362] In Vitro Immunogenicity for MHC Class I Presented Peptides

    [0363] 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*44 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 Table 10b).

    [0364] In Vitro Priming of CD8+ T Cells

    [0365] 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-A*02 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.

    [0366] 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.

    [0367] 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.

    [0368] 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).

    [0369] pMHC used for positive and negative control stimulations were A*0201/MLA-001 (peptide ELAGIGILTV (SEQ ID NO. 519) from modified Melan-A/MART-1) and A*0201/DDX5-001 (YLLPAIVHI from DDX5, SEQ ID NO. 520), respectively.

    [0370] 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.sup.6 CD8+ T cells with 2×10.sup.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 4 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 5 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, Oregon, 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).

    [0371] 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 7 peptides of the invention are shown in FIGS. 3A through 3G together with corresponding negative controls. Results for 36 peptides from the invention are summarized in Table 10a and results for 56 peptides from the invention are summarized in Table 10b.

    TABLE-US-00012 TABLE 10a in vitro immunogenicity of HLA class I peptides of the invention Exemplary results of in vitro immunogenicity experiments conducted by the applicant fo rthe peptides of the invention. <20% = +; 20%-49% =  ++; 50%-69% = +++; > = 70% = ++++ Seq ID No Sequence Wells positive [%] 459 KEVDPAGHSY ++ 460 SEFMQVIF + 461 MEVDPIGHVYIF + 463 QEMQHFLGL + 467 FEYDFLLQRI + 468 QEQDVDLVQKY + 469 SEAFPSRAL +++ 470 EDAQGHIW ++ 474 AEEEIMKKI + 476 MEHPGKLLF + 477 VYEKNGYIYF ++++ 479 QENSYQSRL + 485 NEHPSNNW + 487 LEMPHYSTF +++ 488 SENPETITY ++ 489 SEYADTHYF +++ 490 TENRYCVQL ++ 491 YEVDTVLRY + 492 AEHNFVAKA + 494 KEITGFLLI ++ 495 RENQVLGSGW +++ 496 AEIGEGAYGKVF ++ 497 GEGAYGKVF +++ 500 QEVLLQTFL + 501 KEGDLGGKQW + 504 KESQLPTVM ++ 506 QESDLRLFL + 508 AESEDLAVHL + 509 AESEDLAVHLY + 510 SEDLAVHLY ++++ 511 AEAVLKTLQEL + 512 AEPLVGQRW ++++ 513 AEKDGKLTDY + 515 AEGGKVPIKW ++ 516 DEYLIPQQGF + 518 FELPTGAGL ++

    TABLE-US-00013 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. <20% = +; 20%-49% = ++; 50%-69% = +++; > = 70% = ++++ Seq ID No Sequence Wells positive [%]   4 AEALGAAKKL +   6 AELVGPVIPQDW ++   7 SESDLVNFI +   9 MEVDPIGHLYIF +++  11 EENIVAIGI +++  12 KEVDPTGHSF +  13 VEAQDRETW ++  15 MEAELVRRI +  16 NESDRLVYF ++  17 SEIYQPRGF ++++  18 QEAPRPASSL +  19 MEHSDENIQFW ++  20 LEALLSDLF ++  22 TEEITEGVW +  24 EELALRIGL ++++  25 SEKEPGQQY ++  28 QEFPAHSL +  29 TENPKKFKI ++++  30 EEFCFSVRF +  31 MESAKETRY +  32 REYEYDLKW +  33 IEYENQKRL ++  35 RELVHMINW ++  36 LEQASRIWSW ++++  37 IEQGRWLW ++++  39 AEAMGKFKQCF +  40 REVDPDDSYVF +  41 EENTGKTYF ++  42 SEENTGKTYF ++  44 SEFGAPRW ++++  45 EEINELNRMI +++  47 TEVHSSPAQRW +++  49 SEYVHSSF +  51 VEMTGKHQL ++  53 KEDNPSGHTY ++  54 QEISAHRTEF +  56 ALEEGGGYIF +  57 SEATHHTI ++++  59 AEIEADRSYQ +  60 EEAVRSVAF ++  61 AEYSVHKI +  62 AEYSVHKITSTF +  66 AEVTLNNTI +  68 NEIDIHSIYF ++  69 DENIQKFIW ++  70 AEAEEAMKRL ++  71 AEVGDIIKV ++  72 AEVGDIIKVHF ++  73 GEGTLRLSW ++  78 TEFSNHINL ++  79 TEAQRLDCW +  80 TEQSLYYRQW ++++  83 TEGGTQKTF ++++ 420 MEVDPIGHVY + 421 TEDYSKQAL + 422 EEAQWVRKYF ++++

    Example 4

    [0372] Synthesis of Peptides

    [0373] 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 >50%. All TUMAPs are preferably administered as trifluoro-acetate salts or acetate salts, other salt-forms are also possible.

    Example 5

    [0374] MHC Binding Assays

    [0375] 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)

    [0376] 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.sub.2SO.sub.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.

    [0377] MHC:peptide binding results for 439 peptides from the invention are summarized in Table 11.

    TABLE-US-00014 TABLE 11 MHC class I binding scores. Binding of HLA-class I restricted peptides to HLA-B*44:05 was ranged by peptide exchange yield: >10% = +; >20% = ++; >50 = +++; >75% = ++++ Peptide Seq ID No Sequence exchange   1 KEVDPASNTYTL ++   2 EEFLRPRSL ++   3 DEIFTNDRRW ++   4 AEALGAAKKL ++   6 AELVGPVIPQDW +++   7 SESDLVNFI +++   9 MEVDPIGHLYIF ++++  10 SEYPTKNYV ++  11 EENIVAIGI +++  12 KEVDPTGHSF +++  13 VEAQDRETW ++  14 EMPGGPVW +++  15 MEAELVRRI +++  16 NESDRLVYF +++  17 SEIYQPRGF +++  18 QEAPRPASSL +++  19 MEHSDENIQFW ++  20 LEALLSDLF +++  21 SEAKEIKSQL +++  22 TEEITEGVW ++++  24 EELALRIGL +++  25 SEKEPGQQY ++  26 EESSSPVDEY ++  27 GETCVRITY +++  28 QEFPAHSL +++  29 TENPKKFKI +++  30 EEFCFSVRF +++  31 MESAKETRY +++  32 REYEYDLKW ++++  33 IEYENQKRL ++  34 AEPPILYSEY ++  35 RELVHMINW ++++  36 LEQASRIWSW ++++  37 IEQGRWLW ++++  38 DEVRFFKGNKY ++  39 AEAMGKFKQCF +++  40 REVDPDDSYVF +++  41 EENTGKTYF +++  42 SEENTGKTYF +++  44 SEFGAPRW +++  45 EEINELNRMI +++  46 SELGLPKEV ++  47 TEVHSSPAQRW +++  49 SEYVHSSF ++  50 SEYVHSSFSGF +++  51 VEMTGKHQL ++  52 EDNPSGHTY ++  53 KEDNPSGHTY +++  54 QEISAHRTEF +++  55 TEFHMQFSY ++++  56 ALEEGGGYIF +  57 SEATHHTI +++  58 KEMDPSRQSY +++  59 AEIEADRSYQ ++  60 EEAVRSVAF +++  61 AEYSVHKI +++  62 AEYSVHKITSTF ++++  64 EEYQDSFERY ++  65 SESMVESKF ++  66 AEVTLNNTI +++  67 TEGAVEVKY ++  68 NEIDIHSIYF ++++  69 DENIQKFIW +++  70 AEAEEAMKRL +++  71 AEVGDIIKV ++  72 AEVGDIIKVHF +++  73 GEGTLRLSW ++++  74 AELEGALQKA ++  75 LETSCGSSTAY +  76 RLNEHPSNNW ++  77 QETLAESTW +++  78 TEFSNHINL +++  79 TEAQRLDCW +++  80 TEQSLYYRQW +++  81 GEKATMQNL ++  83 TEGGTQKTF +++  84 AETSYVKVLEY +++  85 SEIDEKVTDL +++  86 QTLKAMVQAW +++  87 GEARGDQVDW ++++  88 KEFTVSGNIL ++++  89 KEFYPVKEF ++  90 EESLLSSW +++  91 EESLLSSWDF +++  92 KEPSQSCIAQY +  93 SEAGLTANQY +++  94 SLAELIAKDW ++  95 AAFEDAQGHIW ++++  96 MDELEEGESY +  97 ELVHMINW ++  98 SEESAGPLL +++  99 SECVKSLSF ++++ 101 SEENTGKTY +++ 102 TELADLDAAW ++++ 103 AELFLTKSF ++++ 105 EEIFKTLNY +++ 106 SVISDSPRSW +++ 107 YQENPRAAW ++ 108 QETNKVETY +++ 110 EVEVGEVKSW + 111 QEIDQKRLEF ++ 112 AEIEADRSYQH +++ 113 MEFKTLNKN ++ 114 VEVNGVPRW ++++ 115 QEPFTRPVL +++ 116 AEANPRDLGASW +++ 117 SEVPVDSHY +++ 118 SEVPVDSHYY +++ 119 VEVKYEGHW ++++ 120 VTEGAVEVKY + 121 YENIPVDKV +++ 122 GESVSWHLF +++ 123 DEINHQSL ++ 124 NENLDYAIL ++++ 125 LEVLHQGQW +++ 126 SEASQSPQY +++ 127 RYFDENIQKFIW +++ 128 TELTEARVQVW +++ 129 EEAMKRLSY ++ 130 REYQEVMNSKL +++ 131 RESHLTEIRQY ++ 132 AESFTSGRHYW ++++ 133 IEAPKLMVV + 134 IEIKDRLQL +++ 135 QEIDRGQYI ++++ 136 EEMPEEIHL +++ 137 EKGLISAF ++ 138 KEAPNIVTL ++++ 139 AESDFSNNML +++ 140 TEHSGIYSC ++ 141 SEKWFRMGF +++ 142 QELFLHPVL ++++ 143 HEHIRSHW +++ 144 IEAYLERIGY +++ 145 EELRMLSF ++ 146 MEELRMLSF +++ 147 RMLSFQQMTW ++ 148 KESDAGRYY +++ 149 AETEPERHLG ++ 150 SEVFHVSEA ++ 151 TELQIPSF ++ 152 HENLIEDF +++ 153 IEIILLSGSL ++++ 154 NEAGEMIKHY ++ 155 TEDARHPESW ++++ 157 SQDVAGTTF ++ 158 VEEERYTGQW +++ 159 EEVQDGKVI ++ 160 AEIATTGQLY +++ 161 GESSEVKAVL +++ 162 EAYDIELNKW +++ 163 AEDEDGKIVGY ++ 164 DEDGKIVGY ++ 165 EEIEAHIAL +++ 166 EEQDFINNRY ++++ 167 AETENRYCV +++ 168 EEGPSVPKIY ++ 169 KEHNSSVPWSS ++++ 170 REMFVFKDQW ++++ 171 WEVVHTVF ++ 172 RENPGMFSW +++ 173 SEHSLEGQKF +++ 174 DENDAGNLITF +++ 176 GETQQHIQL +++ 177 LEEPMPFFY + 178 MEGAALLKIF +++ 179 EEHIFSAF ++ 180 EEHSSKLQTSL ++++ 181 HEVAQDDHL ++ 182 EELHAALSEW ++++ 183 KEMQVTISQQL ++++ 184 EEQLLQKVM ++++ 185 TEANVQALF ++++ 186 EEIFAHLGL +++ 187 TEQALRLSV ++++ 188 AEFVPKADLL +++ 189 ALNGDIYVW ++++ 190 NEAGEVSKHF +++ 191 AEHDMKSVL +++ 192 LEIMTNLVTL ++++ 193 RELRPLFDRQW +++ 194 TEGDVLNYIF +++ 195 MEIKGTVTEF +++ 196 TELEVKIRDW ++++ 197 NEILTIHF ++ 198 REEEANWL +++ 199 AELPENLKALF +++ 200 KELSVFKKF +++ 201 MEILWKTLT ++++ 202 RELPLVLLA ++ 203 REILHAQTL +++ 204 YERPTLVEL +++ 205 MEIEGAGNFL ++++ 206 SEDPEKYYL +++ 207 LEGGGRGGEF ++ 208 SEFLLRIF ++ 209 AEGEPPPAL +++ 210 AEGEPPPALAW +++ 211 LEMLDAHRL +++ 212 SEASVYLFRF +++ 213 DEDLFHKL ++ 214 SVNPIIYGF ++ 216 AGSPVMRKW ++ 217 EVEVGDRTDW ++ 218 REAEEKEAQL +++ 219 WEVEVGDRTDW +++ 220 EEEVFSGMKL ++++ 221 KEAFGPQAL ++++ 222 SEDTIHTHL +++ 223 SEVEGLAFV +++ 224 TETDIDREY ++ 225 VEAATVSKW +++ 226 AEDNMVTSY +++ 227 ALTEDSIDDTF + 228 LEYEAPKLY ++ 229 AEDLEKKYA ++ 230 AEALVDGKW +++ 231 AEALVDGKWQEF +++ 232 YEIRAEAL ++ 233 QEDKATQTL ++++ 234 TEEPQRLFY + 235 SESLPRAPL +++ 236 LEDQLKPMLEW +++ 237 QEIGQKTSV +++ 238 VEDDNYKLSL +++ 239 DEDYTYLIL ++ 240 MELQVSSGF +++ 241 QELLDIANYL ++++ 242 CDAQIQYSY +++ 243 VEQINISQDW ++++ 244 VESSQAFTW +++ 245 MEFQGPMPAGM +++ 246 HEHGLFNLY +++ 247 KESMLKTTL +++ 248 KESQLPTVMDF +++ 249 YEMAIYKKY ++++ 250 AELDHLASL +++ 251 DESADSEPHKY + 252 EEFIGKIGI ++ 253 QEILHGAVRF +++ 254 QEVAGYVLI +++ 255 KQWEYNEKLAF + 256 RLLPGKWW ++ 258 IEVSSPITL ++++ 259 IEVSSPITLQAL ++ 260 VELMFPLLL +++ 261 QEWDPQKTEKY +++ 262 YENILNAI ++ 263 AEQLRGFNA +++ 264 RELIKAIGL +++ 265 EDNLIHKF ++ 266 EEEDRDGHTW +++ 267 VELEVPQL ++ 268 EDLAVHLY + 269 SEDLAVHL ++++ 271 REDLVGPEV +++ 272 SEQNIQRANLF +++ 273 TEFELLHQV +++ 274 DEIDKLTGY ++ 275 GEQPPEGQW +++ 276 SEYQDGKEF ++ 277 VEFPATRSL +++ 278 DQVTVFLHF + 279 GEPVTQPGSLL +++ 280 AAEPLVGQRW ++ 281 HEIPQESL + 282 KEFGIGDLVW ++++ 283 VEEEISRHY ++ 284 SQYPHTHTF +++ 285 AEHPDFSPCSF +++ 286 DELSVGRY ++ 287 REVSVVDIL ++++ 288 TEHFLKKFF +++ 290 AECILSKRL +++ 291 DEQLLLRF ++ 292 HELALRQTV ++++ 293 QEDEQLLLRF +++ 294 EEWEWIQKL ++++ 295 QELEQEVISL +++ 296 AETIFIVRL ++ 297 DEYLIPQQGFF ++ 298 KEVASNSEL +++ 299 AEVQIARKL +++ 300 KQTEATMTF ++ 301 AERIMFSDL ++++ 302 EGEDAHLTQY ++ 303 GEDAHLTQY ++ 304 RELGFTEATGW ++++ 305 AEKNRRDAETW ++++ 306 RRHPSFKRF + 307 YEQLLKWTW ++++ 308 EEPKIDFRVY +++ 309 SDDLRNVTW ++++ 310 FELECPVKY +++ 311 REKDLPNYNW ++++ 312 KEWEREKAVSL +++ 313 EEINQGGRKY +++ 314 EMREERKF ++ 315 MEQQSQEY +++ 316 RLWPEPENW ++ 317 TEFQQIINL ++++ 318 SESSSFLKV +++ 319 YEWEPFAEV + 320 AENPLNIFY ++++ 321 AENPLNIFYI +++ 322 REESDWHYL +++ 323 SETAWN VTY ++++ 324 QELSSIRQF +++ 325 AEQEIMKKV ++++ 326 RELLDFSSW ++++ 327 SEQHSLPVF +++ 328 HENGVLTKF ++ 329 SEPQITVNF +++ 330 SEHLFGTSY +++ 331 KELEATKQYL +++ 332 SEADWLRFW ++++ 333 SEGTLPYSY ++ 334 LEWQNSSSM +++ 335 SETPTLQGL +++ 336 QEVNISLHY ++++ 337 VEVIPEGAML +++ 338 AEMKFYWI +++ 339 NEVKEIKGY +++ 340 GELAPSHGL +++ 341 HELESENKKW +++ 342 SENKKWWEF ++ 343 SEFDLEQVW ++++ 344 DEIRVFGY ++ 345 AEYQAAILHL +++ 346 EEIENLQAQF ++ 347 LENPHVQSV +++ 348 SEVLLTSISTF ++++ 349 LEWQHPSSW ++++ 350 EEMLENVSL +++ 351 EEGRVYVY ++ 352 QEDELVKIRKY +++ 353 AETEEGIYW ++++ 354 TEIMEKTTL +++ 355 SETSTGTSV ++ 356 TEAVLNRY ++ 357 AELMDKPLTF +++ 358 TEFHGGLHY +++ 359 NEFRRKLTF +++ 360 DEMENLLTY ++++ 361 EDASLMGLY ++ 362 SEVEYINKY +++ 363 EECDKAFHF +++ 364 EECDKAYSF ++ 365 NESGKAFNY ++++ 366 EECGKAFKKF +++ 367 TEFAVKLKI +++ 368 KEKVPGITI +++ 369 KELEERMLHW ++++ 370 EEVLLANALW +++ 371 NEIGQELTGQEW ++++ 372 EEYKFPSLF +++ 373 REDPIVYEI ++ 374 NEAEWQEIL +++ 375 HEATFGEKRF +++ 376 SESDGIEQL +++ 377 AEDARGWTA ++ 378 QELFLQEVRM +++ 379 AENRVGKMEA ++ 380 EECGKAFRVF +++ 381 QELMAFSFAGL ++++ 382 SELNPLALY +++ 383 EEMERDLDMY +++ 384 LDGIPTAGW +++ 385 LEHPFLVNLW ++++ 386 EESDYITHY +++ 387 GEVQENYKL +++ 388 VEIVTIPSL +++ 389 DEQRRQNVAY ++ 390 GEYNKHAQLW ++++ 391 TESIGAQIY +++ 392 TEVSVLLLTF +++ 393 SETILAVGL +++ 394 SEILRVTLY +++ 395 AEDFVWAQW ++++ 396 MELLFLDTF ++ 397 EECGKAFSVF +++ 398 AEIIRYIF + 399 IEQADWPEI ++ 400 TELGLFGVW ++++ 401 VENIFHNF ++ 402 IETSSEYFNF +++ 403 QESVHVASY ++++ 404 AEREQVIKL ++++ 405 YEHAFNSIVW ++++ 406 GETVVLKNM +++ 407 MEFQNTQSY +++ 409 QEAKPRATW +++ 410 RELEEEFYSL +++ 411 AERDLNVTI +++ 412 EESFDSKFY +++ 413 TELEPGLTY +++ 414 AEGYLDLDGI ++ 415 EEAGFPLAY +++ 416 DELMRKESQW +++ 417 EESFRCLPEW ++++ 418 GEPRKLLTQDW +++ 419 SELSLLSLY +++ 420 MEVDPIGHVY +++ 421 TEDYSKQAL +++ 422 EEAQWWRKYF +++ 423 KEAINLLKNY +++ 424 EEHVYESIIRW +++ 425 KEVDPASNTY +++ 426 AESLFREAL +++ 427 AEMLGSWGNW +++ 428 AEEKAAVTSL +++ 429 RETEDYSKQAL ++ 430 RELARWTL ++++ 431 QELLDFTNW ++++ 432 TEENGFWYL ++++ 433 AEEGPSVPKIY +++ 434 AEQQQQQMY +++ 435 FETEQALRL +++ 436 AEADLSYTWDF +++ 437 HEDPSGSLHL +++ 438 AELDSKILAL +++ 439 VEVGDRTDW +++ 440 QEVAQVASA ++ 441 QEVAQVASAIL ++++ 442 KESDAGKYY +++ 443 EEYAGQITL +++ 444 SESALQTVI +++ 445 QEVGEITNL +++ 446 AENIKKFLY +++ 447 KEFGLDSVEL +++ 448 ALSPVPSHW +++ 449 RENDFEPKF +++ 450 REIENGNSF +++ 451 REYEDGPLSL +++ 452 NEVDGEYRY +++ 453 SESKVFQLL +++ 454 SESSSAFQF +++ 455 QESVHVASYYW ++++ 456 SESPIRISV +++

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