TW201204386A - Immunogenic peptides of tumor associated antigen L6 and uses thereof in cancer therapy - Google Patents

Abstract

An immunopeptide containing a T cell epitope from the tumor associated antigen L6 (TAL6) and a nucleic acid encoding the immunopeptide. The immunopeptide and its encoding nucleic acid can be used as a component of an immune composition for enhancing immune response against cancer cells that express TAL6.

Description

201204386 VI. Description of the Invention: [Technical Field] The present invention relates to an immunopeptide comprising a tau cell epitope derived from a tumor-associated antigen L6 (TAL6), and a nucleic acid encoding an immunopeptide. [Prior Art] RELATED APPLICATIONS This application claims the benefit of the benefit of the benefit of the benefit of the benefit of the benefit of the benefit of the benefit of the benefit of the benefit of the benefit of the benefit of the benefit of the present disclosure. BACKGROUND OF THE INVENTION Tumor-associated antigen L6 (a member of TAL(10) in the T4 superfamily (TM4SF) is a species that is expressed in various cancer cells, such as lung cancer, breast cancer, colorectal cancer, and cancer cells. The study found that anti- appeal TAL6 antibody can produce antibody-dependent cytotoxicity against TAL6-expressing cancer cells and inhibit tumor growth in nude mice, indicating that TAL6 is a target antigen that can be used in cancer immunotherapy. A cancer vaccine based on the tau lymphocyte (CTL) epitope is a viable anticancer drug. This cancer vaccine contains a CTL epitope derived from a tumor-derived antigen to induce tumors against the target antigen. The cell's bungee I* produces T, ''Field I response, thereby destroying the tumor cells. For the development of a cancer vaccine based on the ctl epitope, the 201204386 CTL-antigen table was identified from the tumor target antigen. The present invention is characterized in that, in one aspect, the invention features an isolated immunopeptide having up to 5 amino acids, which comprises a tumor-associated antigen L0 (TAL6). Amino acid sequence of a T cell epitope, or a nucleic acid encoding such an immunopeptide. The term "isolated peptide" as used herein means a peptide substantially free of natural association molecules, ie The dry weight of the preparation containing the peptide accounts for up to 20% of the natural association molecules. The purity can be measured by any suitable method such as column chromatography, polypropylene gel electrophoresis, HPLC and the like. An example 'This immunopeptide contains an HLA-A2-specific T-cell epitope

Position, eg CIGHSLVGL (SEQ ID NO: 1), SLVGLALLC (SEQ ID NO: 2) 'ALLCIAANI (SEQ ID NO: 3) 'LLMLLPAFV (SEQ ID NO: 4) 'MLLPAFVFI (SEQ ID NO: 5) > AMLSSVLAA (SEQ ID NO: 6), MLSSVLAAL (SEQ ID NO: 7), SVLAALIGI (SEQ ID NO: 8), GLAEGPLCL (SEQ ID NO: 9), HIVEWVSL (SEQ ID NO: 10), SILLALGGI (SEQ ID NO: Lll), ALGGIIFIL (SEQ ID NO: 12) or VINGVLGGI (SEQ ID NO: 13). In another example, the immunopeptide comprises an HLA-A24-specific T-cell epitope, such as CYGKCARCI (SEQ ID NO: 14) ' HSLVGLALL (SEQ ID

NO: 15), LYFPNGETKY (SEQ ID NO: 16), KYASENHLS (SEQ)

ID NO: 17) 'RFVWFFSGI (SEQ ID NO: 18) 'FFSGIVGGGL (SEQ 201204386

ID NO: 19) > GYCVIVAAL (SEQ ID NO: 20) 'TFASTEGQYL (SEQ ID NO: 21), QYLLDTSTW (SEQ ID NO: 22) and EWNVSLFSI (SEQ ID NO: 23). In addition to the TAL6-derived T-cell epitope, the immunopeptide of the present invention may further comprise a T helper stimulating fragment, for example

QYIKANSKFIGITE (SEQ Π) NO: 24) or AKFVAAWTLK (SEQ ID NO: 25) ' and/or an endoplasmic reticulum stem sequence (eg, MRYMILGLLALAAVCSA; SEQ ID NO: 26). In another aspect, the invention features an immunological composition comprising any of the foregoing immunopeptides, a pharmaceutically acceptable carrier and, if desired, an adjuvant. The immunological composition can be used to treat cancer (e.g., lung cancer, breast cancer, colon cancer, or ovarian cancer) or to enhance an immune response against TAL6.

In yet another aspect, the invention features an antibody that specifically binds to a TAL6 fragment having an amino acid sequence selected from the group consisting of CIGHSLVGL (SEQ ID NO: 1) > SLVGLALLC (SEQ ID NO: 2) &gt ; ALLCIAANI

(SEQ ID NO: 3), LLLMLAFAV (SEQ ID NO: 4), MLLPAFVFI (SEQ ID NO: 5), AMLSSVLAA (SEQ ID NO: 6), MLSSVLAAL (SEQ ID NO: 7), SVLAALIGI (SEQ ID NO: 8), GLAEGPLCL (SEQ ID NO: 9), HIVEWNVSL (SEQ ID NO: 10), SILLALGGI

(SEQ ID NO: 11). ALGGIEFIL (SEQ ID NO: 12) > VINGVLGGI (SEQ ID NO: 13) > CYGKCARCI (SEQ ID NO: 14) > HSLVGLALL (SEQ ID NO: 15), LYFPNGETKY (SEQ ID NO: 16), 201204386

KYASENHLS (SEQ ID NO: 17), rfvWFFSGI (SEQ ID)

NO: 18) 'FFSGIVGGGL (SEQ ID NO: 19) > GYCVIVAAL (SEQ ID NO: 20), TFASTEGQYL (SEQ ID n: 21), QYLLDTSTW (SEQ Π) NO: 22) and EWNVSLFSI (SEQ ID NO: twenty three). The present invention also encompasses (1) a pharmaceutical composition for treating cancer or enhancing an immune response against TAL6, the pharmaceutical composition comprising any of the aforementioned immunopeptides, or a performance vector for producing the peptide, and (2) The use of the immunopeptide or the expression carrier for producing the same for the manufacture of the desired drug. The details of one or more specific aspects of the invention are set forth in the embodiments below. Other features and advantages of the present invention will be apparent from the following description and drawings. [Embodiment] The present invention features an immunopeptide having up to 50 amino acid residues. The immunopeptide comprises a T-cell epitope (e.g., a CTL epitope) derived from TAL6 and specific for a particular hla allele, such as HLA-A2 or HLA-A24. A tau cell epitope refers to a peptide that is capable of activating tau cells and subsequently eliciting an immune response mediated by activated tau cells. A CTL epitope refers to a peptide that is capable of activating CTL (also known as Tc or killer tau cells), which in turn stimulates CTL responses, i.e., includes abnormal cells (e.g., via sputum infection or tumor cells). The CTL epitope (representatively comprising an 8-11 amino acid residue) forms a complex with a specific class I 201204386 MHC molecule (including the heavy chain and β2 microglobulin) present on the surface of the antigen-presenting cell. When the complex binds to a sputum cell receptor of a sputum cell (e.g., CD8 sputum cell), it activates the sputum cell and then initiates a CTL response. TAL6 is a known tumor marker that is expressed on a variety of cancer cells. The amino acid sequence is listed below (SEQ ID NO: 30):

Met Cys Tyr Gly Lys Cys Ala Arg Cys lie Gly His Ser Leu Val Gly Leu Ala Leu Leu Cys lie Ala Ala Asn lie Leu Leu Tyr Phe Pro Asn Gly Glu Thr Lys Tyr Ala Ser Glu Asn His Leu Ser Arg Phe Val Trp Phe Phe Ser Gly lie Val Gly Gly Gly Leu Leu Met Leu Leu Pro Ala Phe Val Phe lie Gly Leu Glu Gin Asp Asp Cys Cys Gly Cys Cys Gly His Glu Asn Cys Gly Lys Arg Cys Ala Met Leu Ser Ser Val Leu Ala Ala Leu lie Gly Lie Ala Gly Ser Gly Tyr Cys Val lie Val Ala Ala Leu Gly Leu Ala Glu Gly Pro Leu Cys Leu Asp Ser Leu Gly Gin Trp Asn Tyr Thr Phe Ala Ser Thr Glu Gly Gin Tyr Leu Leu Asp Thr Ser Thr Trp Ser Glu Cys Thr Glu Pro Lys His lie Val Glu Trp Asn Val Ser Leu Phe Ser He Leu Leu Ala Leu Gly Gly He Glu Phe lie Leu Cys Leu lie Gin Val lie Asn Gly Val Leu Gly Gly lie Cys Gly Phe Cys Cys Ser His Gin Gin Gin Tyr Asp Cys ° T cell epitope derived from TAL6 can be identified by the following method. Peptides spanning the entire TAL6 amino acid sequence (e.g., containing 8-12 amino acid) can be prepared by conventional methods (e.g., chemical synthesis). The effect specific to a particular HLA allele is determined by analysis known in the art. The MHC-peptide complex formation assay was performed in a real J to determine the tal6-like class I HLA-specific side. The heavy chain and p2 microglobulin encoded by the 吼-type 吼8 allele (e.g., HLA-A2 or HLA-A24) are expressed and purified. 201204386 then mixes them with any of the foregoing peptides and can detect any of the MHC-peptide complexes formed thereby by, for example, biliary detection. It is well known that heavy chains encoded by a particular class of alleles will form a complex with P2 microglobulin only in the presence of a peptide having such an allele. Therefore, the formation of the MHC_peptide m complex means that the peptide contains an epitope specific to the disordered allele of the first class. After determining that a TAL6 peptide is specific for a HLA allele, it can then be analyzed in vitro or in vivo to determine if it contains a sputum epitope (e. g., a CTL epitope). The following is an example of an in vitro assay. Humans with a Class I HLA allele are identified by genotyping using methods known in the art. Collect his or her peripheral blood mono- and cell (PBMC)' and expose it to this condition in the presence of self-anti-secret cells. If the synthetic peptide activates PBMC, the epitope included in the epirubic cap is a tau cell epitope specific for the class I HLA allele. In another embodiment, the in vivo assay is used to determine that the peptide branch comprises a tau cell epitope. A thief-made mouse of the class 1 HLA heterogene is immunized with the peptide. Induction of an immune response (e.g., secretion of a cytokine such as IFN_y and n-_2 or induction of cytotoxicity) indicates that the peptide contains a tau cell epitope specific for the class I HLA allele. The immunopeptide of the present invention may further comprise a tau helper cell stimulating tablet #又的, for example, QYIKANSKFIGITE (tetanus toxoid 830-843; SEQ ID N: 24) or AKFVAAWTLK (PADRE peptide; SEQ ID NO: 25). Or 201204386

Alternatively or additionally, it may further comprise an endoplasmic reticulum dry sequence. This stem sequence facilitates entry of the polypeptide containing it into a class I antigen display pathway wherein the T-cell epitope of the polypeptide can form a complex with the class J Hla molecule. Examples of target sequences include the peptides MRYMILGLLALAAVCISA ID and RYMILGLLALAAVCSA (SEQ ID ΝΟ: 27), both derived from the adenocarcinoma 毋Ε3 protein. Other standard sequence includes, but is not limited to, MRAAGIGILTVAAAAAG (SEQ ID NO: 28, see Minev et al. 2000, Eur J Immunol 30(8): 2115-24), and peptide MAGILGFVFTLAAAAAG (SEQ ID NO: 29, see Gueguen et al., 1994, / 细 she i/· 1994, 180(5): 1989-94). The immunopeptide of the present turtle can be obtained by a conventional method such as chemical synthesis of a polypeptide or a recombinant technique. To prepare a recombinant peptide, the nucleic acid encoding the same can be ligated to another nucleic acid encoding a fusion partner, such as glutathione-s-transferase (GST), 6x_His tag or Ml3 gene 3 protein. The resulting fusion nucleic acid is expressed in a suitable host and can be isolated from the fusion protein by methods known in the art. The isolated fusion protein can be processed further (e.g., by enzymatic decomposition), and the fusion partner' is removed and the recombinant immunopeptide of the invention is obtained. If the immunopeptide contains a _ cell anti-county position derived from TAL6 (a cancer target antigen), it can be used to enhance the fight against cancer, such as lung cancer, colon cancer, breast cancer, ovarian cancer, gastric cancer, Kaposi's sarcoma and liver cancer. The immune response (eg 'CTL reaction'). This composition is effective for treating cancer when administered to an individual (better with HLA-A2, HLA-A24 or equivalent melon VIII gene). HLA-A) or HLA_A24 is equivalent to the 201204386 allele, which is an allele that is specific for the cross-reaction of the peptide from 24 to the melon. Examples include, but are not limited to, hla_a3 and hla_ai, which are used to treat cancer or enhance an immune response against TAL 6 in an individual having the same ability - a pre-existing immunopeptide, or an expression vector capable of expressing the immunopeptide Mix with a pharmaceutically acceptable carrier to form an immunogenic composition (eg, a vaccine). Immunopeptides may need to be chemically modified first because they may not have a significant long half-life. Chemically modified peptides or peptide analogs include any of the functional chemical equivalents of the peptide that increase the stability and/or efficacy of the present invention in vivo or in vitro. The term peptide analog also refers to any amino acid derivative of a peptide as described herein. Peptide analogs may be modified by, including but not limited to, contralateral linkages, incorporation of non-natural amino acids and/or their derivatives during peptide synthesis, and procedures using parent & agents, with others A method for forcibly structuring a peptide or an analog thereof is prepared. Examples of side chain modifications include modification of an amine group, such as by reductive ortho-reaction with NaBH4 reduction by reaction with an acid; sub-axis side with methyl acetimimine; Side; amine-based hydration with aromatic acid; amine and 2,4,6-trinitrophenyl tartaric acid (tnbs) trinitro alum-based sin; silk and succinic anhydride and four Thieves _ looking for the role of basalization; and lysine and pyridinium _5, _ phosphate ester followed by thiolation of NaBH4 reduction. The thiol group of arginine can be modified by forming a heterocyclic condensation product with a reagent such as 2,3-butanedione, phenylglyoxal and glyoxal. The thiol group can be modified by the activation of carbodiimide formed by hydrazine-hydrazinoisourea followed by derivatization 201204386 (for example) in the corresponding decylamine. The sulfhydryl group may be catalyzed by, for example, iodine with iodoacetic acid or iodine with decylamine; oxidized to form cystine by peroxyformic acid; mixed disulfide with other thiol compounds; with maleic imine, maleic anhydride Or other substituted & imine reactions using 4-chloromercury benzoate, 4-chloromercuric acid, phenylmercuric chloride, 2-mercury-4-nitrophenol and other mercury-based compounds to form mercury a base derivative; modified with an acid carbamate at a pH of cyanic acid. The tryptophan residue can be oxidized by, for example, (iv) succinyl (tetra) imine, or its alkylation with oxacyclohexane-5-nitro-benzyl or sulfonyl halide. Function modification. The tyrosine residue can be modified by digesting with the four shouts. The 24 ring of the ugly wire can be modified by alkylation of the (tetra) derivative or by N-carbon ethoxylation of diethyl carbonate. Examples of incorporation of non-natural amino acids and derivatives during the synthesis of the month include, but are not limited to, the use of n-leucine, 4-aminobutyric acid, 4-aminol_3, thiol-5- Phenyl phthalic acid, 6 aminocaproic acid, t-butylglycine, ortho-amino acid, phenylglycine, ornithine, _ muscle 夂 4_月女基·3命基_6_ D-isomer of methylheptanoic acid, 2-aminophenylalanine and domain amino acid. The product can be prepared by a conventional method. It comprises the immunopeptide/episome of the present invention, and the acceptable load of the medical red (4), such as a scale-reducing buffer salt, an anthrax salt solution and/or an adjuvant. When the immunopeptide does not include the 辅助-assisted, turf-stimulated fragment as described above, such a fragment may be included in the composition to enhance the immune response, the H Pharmaceutical carriers and diluents suitable for the spear order, as well as pharmaceuticals for their use, must be composed of Reminder Pharmaceutical Sciences (Remingt〇n, s Pharmaceutical Sciences). If necessary, adjuvants such as cholera toxin, Escherichia coli heat-labile endotoxin (LT), liposome, immunostimulating complex (ISCOM) or immunostimulatory sequence oligodeoxynucleotide (ISS_〇DN) may also be used. Included in the compositions of the present invention. The composition may also include a polymer that facilitates delivery in vivo. See Audmn R. et al., Episode-21: 丨 25〇·5, 2〇〇3; and Denis_Mize et al. Ce//Yang Noodles 225:12_2〇, Gang 3. In one example, the immunopeptide is a component of a multivalent vaccine composition against cancer. The multivalent composition contains at least one of the aforementioned immunopeptides, and at least one species is isolated from influenza virus, parainfluenza virus 3, streptococcus faecalis, B. sphaericus, S. aureus or respiratory syncytial disease. Antigen, with or with a new agent. In the other example, the immune system is '’. Zhou Fuwang - a toxic body, which contains a Wei virus outer lining protein, such as the influenza virus hemagglutinin (HA). Methods for preparing vaccines are well known in the art, as exemplified by U.S. Patent Nos. 1,903, 4,599,231, 4,599,230 and 4,596,792. The epidemic field can be SUf as a silky substance as a liquid solution or emulsion. The immunological peptide of the present invention can be combined with a bribe that can be cut into Newcomb. The agent may include water = water, dextrose, glycerin, ethanol, and combinations thereof. The vaccine may further be included in the enhanced epidemic 2 auxiliary substance such as _agent or emulsifier, pH buffer or reagent with $ 01 Shi Ba Hua Ming or Wei 1 Lu (alumina), generally used 0.05 • knife ratio dissolution _ Axis _ Jianshui Silk. The vaccine can be administered parenterally in 201204386 by subcutaneous or intramuscular injection. Alternatively, other forms of administration may be desired to include suppositories and oral formulations. For suppositories, an adhesive and a carrier such as a polyalkylene glycol or a triglyceride may be included. Oral formulations may include excipients for normal use, such as pharmaceutical grade saccharin, cellulose, magnesium carbonate, and the like. Such compositions take the form of a solution 'suspension, tablet, pill, capsule, sustained release formulation or powder' and contain 10-95% of the immunological conditions described herein. The aforementioned immunological composition may also be a dendritic cell-based vaccine which contains dendritic cells of any of the immunopeptides described herein. Methods for preparing dendritic cell-based vaccines are well known in the art. See Slingluff et al., C/z>? Gm(8)12:2342s-2345s, 2006; Buchsel et al., C7z>?J camphor>/ Shi 10:629-40, 2006; and Yamauchi et al., Expert 〇pin Bi〇丨Ther. Ί: 645-9,200 Ί. An effective amount of the composition is administered to an individual (e.g., a human) via a conventional route for treating cancer or enhancing an immune response against TAL6-expressing cells. Exemplary routes of administration include, but are not limited to, oral, parenteral, inhalation spray, topical, rectal, nasal, buccal, vaginal or administration via an implanted container. The term "parenteral" is used herein to include subcutaneous, intradermal, intravenous, intramuscular, intra-articular, intra-arterial, intrasynovial, intra-abdominal, intrathecal, intralesional, and intracranial injection or immersion techniques. The term "effective amount" as used herein, refers to the amount of each active agent that is required to be administered to an individual to produce a therapeutic effect, either alone or in combination with one or more other active agents. Effective sputum (as understood by those skilled in the art) is a function of the route of administration, the use of the excipient, and the use of other active agents. The amount to be administered is 201204386 depending on the body of the body, the body (for example), and, if necessary, the ability of the immune component to synthesize the active ingredient of the drug. The desired polypeptide may be a polypeptide of the present invention in a suitable dosage form. Use: The measured 'and may be different from the range of micrograms, but may include two, the appropriate course of the additional dose may also have an initial. The investment of Wei Xing (4) can also be determined by the route of administration, and the patient of the disease can be changed according to the size of the host. Composition = read 峨 峨 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ If necessary, it may be decided by the skilled person to repeat the administration. For example, after the dose is initiated, three additional doses can be administered at weekly intervals. Additional injections may be given 4 to 8 weeks after the first immunization, and a second addition may be given between 8 and 12 weeks, using the same formulation. Serum or butyl cells can be collected from an individual for testing the immune response elicited by the immunological compositions described herein. Methods for analyzing the cytotoxicity τ (4) package against a certain protein are well known in the art. Additional additions can be given if needed. It is possible to change the amount of the immunopeptide, the dose of the composition and the dosage of the drug, and optimize the immunization procedure to cause the greatest anti-cancer immune response. The immunopeptide of the present invention can also be used to produce antibodies in animals (for the purpose of producing antibodies) or human lice (for the purpose of treating diseases). Methods for making single and multiple antibodies and fragments thereof in animals are known in the art. See, for example, Hari〇w and 14 201204386

Lane, (1988) Antibodies: Laboratory Manual, Cold Spring Harbor Laboratory, New York. The term 'antibody' includes intact immunoglobulin molecules, antigen-binding fragments thereof (eg, Fab, F(ab')2, Fv) 'and genetically engineered antibodies' such as chimeric antibodies, humanized antibodies and singles. Chain antibodies and dAbs (Functional Domain Antibodies; Ward et al. (1989) A^Wre, 341, 544). These antibodies can be used to detect cancers that express TAL6, or for cancer treatment. The antibody can be coupled to a carrier protein (e.g., KLH), mixed with an adjuvant, and injected into a host animal. The antibody produced in the animal can then be purified by peptide affinity chromatography. The host animals used in general include rabbits, mice, and scorpio (4) rats. Various adjuvants that can be used to increase the immunological response are dependent on the host species, and include Freund's adjuvant (complete and incomplete), mineral gel For example, hydrocortisone, CpG, surfactants such as lysolecithin, piur〇nic polyols, polyanions, peptides, oily emulsions, keyhole limpet hemocyanin, and dimethysts can be used. Human adjuvants including BCG (Bacillus Calmette-Guerin) and Corynebacterium bacillus. Multiple antibodies (heterologous antibody molecule populations) are present in the serum of the immunized individual. The monoclonal antibody U is in the same heterogeneous antibody group as the present peptide. Prepared (see, for example, et al. (Cong) Gaya 256, 495; KoWer et al. (1976) · / Fine Coffee / 6, 5ιι; K〇hier et al. (1976) Facial Milk 0/ 6, 292; and Etc. (ΐ98ι) monoclonal antibody and T cell fusion tumor, Elsevier, γ γ). In particular, monoclonal antibodies can be supplemented by any of the molecules used to culture the cells by continuous culture. ^ 201204386 described in Kohler Et al. (1975) Atowre 256, 495 and U.S. Patent 4,376,110; Human B-cell fusion tumor technology (Kosbor et al. (1983) / m Ju 4 72; Cole et al. (1983) oc. ΛΜ·也·· 5W t/like 80, 2026); and EBV-fused tumor technology (Cole et al. (1983) Monoclonal Antibody and Cancer Therapy, Aian R. Liss, Inc., pp. 77-96). A class of immunoglobulins, including IgG, IgM, IgE, IgA, IgD, and any subclass thereof. The fusion tumors of the monoclonal antibodies of the present invention can be produced in vitro or in vivo. Support. In vivo ability of producing high titers of monoclonal antibodies, it may be particularly useful in the manufacturing method. Further, use for the manufacture of "chimeric antibodies ,, and develop the technology. See, for example, Morrison et al. (1984) Household gamma 81, 68S1; Neuberger et al. 312, 604; and Takeda et al. (1984) 314.452. A chimeric antibody is one in which different portions are derived from different animal species' such as those having a variable region derived from a murine monoclonal antibody, and a human immunoglobulin region. Alternatively, a technique for producing a single-chain antibody (U.S. Patent Nos. 4,946,778 and 4,7G4,692) can be applied to produce a single-chain & antibody-based bacterium library. The single-stranded anti-form is formed by bridging the heavy and light chain fragments of the Fv region via an amino acid. Moreover, the anti-segment can be generated by known techniques. For example, such fragments include, but are not limited to, F(ab')2 fragments which can be produced by pepsin decomposition of antibody molecules, and can be bridged by reduction of the disulfide of the F(ab,)2 fragment. The resulting Fab fragment. Antibodies can also be humanized by methods known in the art. For example, there is hope for it. . Monoclonal antibodies can be humanized by commercial methods (s(7)^^ 201204386

Scotland; and 〇xford M〇〗 ecular, Pal〇 Alt〇, Calif). Complete human limbs, such as those found in transgenic animals, are also characteristic of the invention (see, for example, Green et al. (1994) St. G. (10) 7, 13; and U.S. Patent Nos. 5,545,806 and 5,569,825). The invention also features a mononuclear nucleoside encoding an immunopeptide of the invention, comprising a vector which enables the expression of the immunopeptide. Such a nucleic acid can be used (as a vaccine) by passing the nucleic acid to a living vector, such as Salmonella, this sputum,

Adenovirus, facial venom, (iv) viral or non-viral vectors are directly administered to an individual. Nucleic acid-based immunological methods are well known in the art. The following specific examples are merely illustrative and are not intended to limit the remainder of the disclosure in any way. No need to go into the detailed description, it is believed that ^, the skilled farmers can based on the description of the towel, the most complete course of the Japanese limbs, and the published documents cited in this article, all with their integrity : Fan Wei, any mechanism proposed below, does not limit the present in any way; "Example 1. The identification of the 42-specific epitope of the tau-derived cell from the 胤6 protein is determined by: = 16 synthesized (All are derived from self-analysis (described in the special peptides in the hall to form a complex specific to fine, 872), et al. identified 201204386 Table 1. TAL6 peptide and its binding activity to HLA-A2 peptide number TAL6 Positional sequence in the binding activity (〇/〇) 1 9-17 CIGHSLVGL (SEQ ID ΝΟ: 1) 93.30 2 13-21 SLVGLALLC (SEQ ID NO: 2) 125.70 3 18-26 ALLCIAANI (SEQ ID NO: 3) 53.65 4 53-61 IVGGGLLML (SEQ ID NO: 31) ~---- 43.36 5 58-66 LLMLLPAFV (SEQ ID NO: 4) 134.34 6 60-68 MLLPAFVFI (SEQ ID NO: 5) 154.57 7 89- 97 AMLSSVLAA (SEQ ID NO: 6) 114.88 8 90-98 MLSSVLAAL (SEQ ID NO: 7) 162.82 9 93-101 SVLAALIGI (SEQ ID NO: 8) 158.08 10 114-122 G LAEGPLCL (SEQ ID NO: 9) 72.42 11 154-162 HIVEWNVSL (SEQ ID NO: 10) —---- 91.11 12 161-169 SLFSILLAL (SEQ ID NO: 32) 42.57 13 164-172 SILLALGGI (SEQ ID NO: l 1) 51.79 14 168-176 ALGGIEFIL (SEQ ID NO: 12) 112.83 15 177-185 CLIQVINGV (SEQ ID NO: 33) 26.33 16 181-189 VINGVLGGI (SEQ ID NO: 13) 59.06 Brief description of 'according to the following The His-Tag-fused human hla-A2 heavy chain (His-HLA-A2)' and the His-Tag-fused human β2-microglobulin (His_p2) were expressed in Escherichia coli to obtain a His_Tag fusion protein. The expression vector encoding the fusion protein was introduced into E. coli BL2 (DE3). The resulting transgenic strain will be at 37 C. When the O.D. value reached 〇.5, 〇"mM isopropyl ID-thiogalactopyranoside (IPTG) was added to the E. coli culture 201204386. After incubation for 3-4 hours at 37 °C, E. coli cells were harvested by centrifugation at 6000 rpin for 20 minutes. The cell pellet was suspended in a buffer a containing 8 Μ urea, 20 mM HEPES (pH 8.0) and 50 mM NaCl, and then subjected to ultrasonic oscillation. The ultrasonically oscillated cells were again centrifuged, and the thus formed supernatant was collected and loaded onto a Ni-NTA-deficient sugar column to purify him to be _8-2 or His-p2. His-A2, His+2 and various peptides listed in the above table (test peptide) or _ positive control peptides together with l〇〇mMTris_Hcl (pH8), 4〇〇mML_arginine, 2 mM The cells were incubated at 4 ° C for 72 hours in EDTA, 5 mM reduced glutathione, 0.5 mM oxidized glutathione refolding buffer. The method for determining the formation analysis of the MHC-peptide complex is described below. The ELISA plate was covered with anti-HLA antibody W6/32 (HB-95; ATCC.) (50 pL' concentration of 5 pg/ml dissolved in mM carbonate buffer, pH 9.6 at 4 C). The plate was dissolved in pbs at 250 μΐ/well 5% w/v skimmed milk powder at room temperature for 2 hours, then at 300 μΐ/well 0.05. /. Tween-20 (Sigma) was washed three times in PBS. The complex was diluted in PBS containing 1% bSA and then added to the antibody-coated flat plate. The plate was incubated for 2 hours at room temperature to allow the complex to bind to the anti-salt antibody. After incubation, the plate was washed twice, and then rabbit anti-human β2-microglobulin antibody (DAK〇, Japan; 1:25〇〇) labeled with 1 μl/well of oxidative oxidase (HRp) was added. Dilute in PBS solution containing 1% BSA). The plates were incubated for 2 hours at room temperature, washed six times with PBS/0.05% Tween 20, and then __conjugated anti- 19 201204386 rabbit antibody (1:2000) was added. After incubation for one hour at room temperature, add 3,3,_5,5,_tetradecyl phenylamine (TMB, Sigma) to a flat plate, incubate for 3 minutes, and use the EUSa reader at 450 nM The chromaticity thus developed in each well is read. The intensity of the color indicates the MHC-peptide formation rate of the peptide. Based on the peptide formation rate of each peptide relative to the MHC-peptide formation rate of the positive control peptide, the relative binding activity was determined according to the following formula: relative binding activity = (testosterone formation rate of the test peptide - MHC of the blank control peptide) Peptide formation rate) / (Phase of the positive control peptide. Peptide formation rate - MHC-peptide formation rate of the blank control peptide). The relative binding activities of the respective test peptides are shown in Table 1 above. A peptide having a relative binding activity of more than 5% by weight is a T cell epitope specific for HLA-A2. Example 2: HLA-A2 transgenic mice immunized with hlA_A2 specific T cell epitope derived from TAL6 will be one milligram of various HLA-A2-specific T cell epitopes identified in Example 1 above. Peptide (test peptide), and 1 mg pADRE peptide

(AKFVAAWTLKAAA; SEQ ID NO: 25) (both in 0.5 ml PBS) mixed with 0.5 mL of incomplete Freund's adjuvant (IFA). An EBV-derived HLA-A2-specific epitope (ie, GLCTLVAML (GLC; SEQ ID NO: 35)) was used as a positive control group, and EBV-derived

The HLA-A24-specific epitope (ie, tygpvfmcl (tyg; SEqID NO: 37)) was used as a negative control group. A 100 μl mixture (containing 5 测 test peptide) was injected subcutaneously into the base of the tail of HLA-A2 transgenic mice, every 7 days 20 201204386 - a total of two people. Seven days after the second injection, spleen cells were collected from the treated mice and cultured in a secret containing the 1G site test peptide. The supernatant of the cell culture was subjected to ELISpQt analysis, and the total amount of bribe 1 contained in the cap was measured, which was proportional to the activity of the test peptide to stimulate tau cells. As shown in Figure 1, some of the test peptides (e.g., peptides 2 and 5) induce T cells to secrete IFN-[gamma], indicating that they are HLA-A2-specific tau cell epitopes. Example 3: Identification of HLA-A24-specific T cell epitopes derived from TAL6 The TAL6 peptides listed in Table 2 below were subjected to MHC-peptide complex formation analysis according to the procedure described in Example 1 above. To identify MHC complexes that can form human HLA-A24 and β2-microglobulin. The results obtained by this are shown in Table 2 below. A peptide having a relative binding activity greater than 50%, i.e., green is considered to be a TAL6 Τ cell epitope specific for HLA-A24. Table 2. TAL6 peptide and its binding activity to HLA-A24. Sequence number relative binding activity in TAL6. (0/〇) 1 2- 10 CYGKCARCI (SEQ ID NO: 14) ------ 12.73 2 12-20 HSLVGLALL (SEQ ID NO: 15) ——— 61.73 3 22-30 IAANILLYF (SEQ ID NO: 39) 0.00 4 28-36 LYFPNGETKY (SEQ ID NO: 16) 84.95 5 36-44 KYASENHLS (SEQ ID NO: 17) 64.59 6 45-53 RFVWFFSGI (SEQ ID NO: 18) ----- 91.88 --------- 21 201204386 7 49-57 FFSGIVGGGL (SEQ ID NO: 19) 72.36 8 105- 113 GYCVIVAAL (SEQ ID NO: 20) 117.78 9 131 - 139 TFASTEGQY (SEQ ID NO: 40) 49.24 10 131-140 TFASTEGQYL (SEQ ID NO: 21) 115.71 11 138-147 QYLLDTSTW (SEQ ID NO: 22) 110.75 12 154-163 fflVEWNYSLF (SEQ ID NO: 45) 28.03 13 155-163 IVEWNVSLF (SEQ ID NO: 41) 41.01 14 157-165 EWNVSLFSI (SEQ ID NO: 23) 74.01 15 157-166 EWNVSLFSIL (SEQ ID NO: 42) 22.24 16 170-178 GGIEFILCL (SEQ ID NO: 43) 25.29 17 170-179 GGIEFILCLI (SEQ ID NO: 44) 14.85

Example 4: HLA-A24 transgenic mice immunized with HLA-A24-specific T cell epitopes derived from TAL6 were identified as HLA-A24-specific T-cells as described in Example 3 above. The peptide of the epitope (test peptide) was immunized with HLA-A24 transgenic mice according to the procedure described in Example 2 above. The EBV peptides GLC and TYG were used as negative and positive control groups, respectively. As shown in Figure 2, some test peptides (e.g., peptides 11, 13, and 14) induce T cells to secrete IFN-γ, indicating that they are HLA-A24-specific T cell epitopes. Example 5: HLA-A2 transgenic mice were vaccinated to produce TAL6 expression vectors to induce T cell responses specific to TAL6 peptides. Expression vectors pCIneo (Promega, 22 201204386) were used by conventional recombinant techniques.

Madison, WI, USA) constructed to express the plastid pEK/TAL6, which was designed to express an endoplasmic reticulum target sequence, the H_2Kb_specific sequence snNFEKL (SEQ ID NO: 46; derived from imprinted albumin), A fusion protein of GILGF'VFTL (SEQ ID N: 47; μ protein derived from influenza virus) and TAL6. Mice were immunized 2-3 times via intramuscular injection with pEK/TAL6 or pCIne〇 over 3_ cycles. Seven days after the last injection, the immunized mice were sacrificed, and their spleen cells were collected and stimulated with various test TAL6 peptides. The presence or absence of cells secreting lFN-γ activated by the test TAL6 peptide was determined by IFN-γ ELISpot. As shown in Fig. 3, spleen cells derived from pEK/TAL6-immunized mice reacted with peptides 2 and 5 listed in Table 1 above. This result shows that a DNA vaccine expressing TAL6 can induce a T cell response specific to certain specific TAL6 peptides. Example 6: Immunization with TAL6 peptide inhibits HLA-A2 transgenic mice • Tumor growth Peptide 2 or peptide 5 (mixed with IFA) listed in Table 1 above is administered subcutaneously to HLA-A2 Transgenic mice (50 pg/mouse) or wild-type C57BL/6 small milk were administered twice within two weeks. Two days later, each immunized mouse was subcutaneously implanted with 2 X 1〇5 tumor cells EL4/TAL6/HLA-A2 (EL4 cells stably expressing TAL6 and HLA-A2)' for immunized mice. Inducing tumor growth. Tumor size in treated mice was detected every 2 to 3 days. Tumor volume was calculated using the following formula: tumor volume = length X width X width/2. 23 201204386 The immunological action of peptide 5 significantly inhibited tumor growth in HLA-A2 transgenic mice, but did not inhibit tumor growth in wild-type mice. See Figure 4. Immunization with peptide 2 also reduced tumor growth in HLA-A2 transgenic mice, but to a lesser extent. These results show that immunization with a specific immunopeptide derived from TAL6 is effective in inhibiting tumor growth in the carrier of 吼8-8. Other Specific Aspects All of the features disclosed in this specification can be combined in any combination. Thus, the individual features disclosed in this specification can be replaced by alternative rhymes that are identical, equal or similar. The subject matter is merely an example of a series of equivalents or similar features, unless the three lines are clearly. The various features and modifications of the present invention are susceptible to various modifications and alternatives. Therefore, other specific aspects are included in the scope of application for patents. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a graph showing the induction of IFN-y production by spleen cells derived from several 8-58 transgenic mice immunized with several immunopeptides derived from TAL6. "NP," represents the absence of any peptide. Figure 2 is a graph showing the induction of iFN-γ production by spleen cells from 24 201204386 HLA-A24 transgenic small breasts immunized with several immunopeptides derived from TAL6." n, refers to the negative control group, and "N" refers to the positive control group. Figure 3 is a graph showing the petty-induced specific T-cell response immunized with transplasty pEK/TAL6 DNA. iFN_YELISpot analysis was performed to detect cells secreting IFN-γ. "N" refers to the negative control group, and "N, refers to the positive control ^ Figure 4 is a graph showing tumor growth in immunized mice by immunological traits derived from TAL6. Tumor volume is calculated using the following formula: tumor volume = length X width X width/2. Parallel group (8): HLA-A2 transgenic mouse. Parallel group: wild type mouse. [Main component symbol description]

25 201204386 Sequence Listing <110>National Institute of Health<120> immunopeptides of tumor-associated antigens and their use in cancer therapy<130> 38301-014001 <150> 61/233,229 <151> 2009-08-12 <160> 47

<170>Patentln Version 3. 5 <210> 1 <211> 9 <212> PRT <2]3> Artificial Sequence <220> <223>Synthetic HLA-A2 Specific CTL Antigen Epitope (9-] TAL6 7 aa) <400> 1

Cys lie Gly His Ser Leu Val Gly Leu

<210> 2 <211> 9 <212> PRT <2]3> artificial sequence <220><223>synthetic HLA-A2 specific CTL epitope (13-21 aa of TAL6) <400> 2

Ser Leu Val Gly Leu Ala Leu Leu Cys 1 5 <210> 3 201204386 <211> 9 <212> PRT <213>artificial sequence <220><223>synthetic HU-A2 specific CTL antigen Epitope (18-26 aa of TAL6) <400> 3

Ala Leu Leu Cys lie Ala Ala Asn lie 1 5 <210> 4 <211> 9 <212> PRT < 213 > 213 > artificial sequence <220 < 223 > 223 > synthetic HLA-A2 specific CTL epitope Bit (58-66 aa of TAL6) <400〉 4

Leu Leu Met Leu Leu Pro Ala Phe Val 1 5 <210> 5 <211> 9 <212> PRT <213>Artificial Sequence <220> <223>Synthetic HLA-A2 Specific CTL Epitope Bit (60-68 aa of TAL6) <400〉 5

Met Leu Leu Pro Ala Phe Val Phe lie 1 5 <210> 6 <211> 9 <212> PRT <213>Artificial Sequence 201204386 <220> <223>Synthetic HLA-A2 Specific CTL Antigen Epitope (89-97 aa of TAL6) <400〉 6

Ala Met Leu Ser Ser Val Leu Ala Ala 1 5 <210〉 7 <211> 9 <212> PRT <213>Artificial Sequence<220><223>Synthetic HLA-A2 Specific CTL Antigen Table Bit (90-98 aa of TAL6)

<400> 7

Met Leu Ser Ser Val Leu Ala Ala Leu 1 5 <210> 8 <211> 9 <212> PRT <213>Artificial Sequence <220><223>>223 Synthetic HLA-A2 Specific CTL Epitope Bit (93-101 aa of TAL6)

<400〉 8

Ser Val Leu Ala Ala Leu lie Gly lie 1 5 <210> 9 <211> 9 <212> PRT <213>Artificial Sequence <220> <223>Synthetic HLA-A2 Specific CTL Epitope Bit (114-122 aa of TAL6) <400> 9 201204386

Gly Leu Ala Glu Gly Pro Leu Cys Leu 1 5 <210> 10 <211> 9 <212> PRT <2>3>Artificial Sequence<220><223>Synthetic HLA-A2 Specific CTL Epitope (154-162 aa of TAL6) <400> 10

His lie Val Glu Trp Asn Val Ser Leu 1 5 <210> 11 <211> 9 <212> PRT < 213 > 213 > artificial sequence <220 < 223 > 223 > synthetic HLA-A2 specific CTL epitope Bit (164-172 aa of TAL6) <400〉 11

Ser Ile Leu Leu Ala Leu Gly Gly lie 1 5 <210> 12 <211> 9 <212> PRT <213>Artificial Sequence<220><223>>223 Synthetic Plastic HLA-A2 Specific CTL Epitope Bit (168-Π6 aa of TAL6) <400> 12

Ala Leu Gly Gly lie Glu Phe lie Leu 1 5 &lt;210&gt; 13 201204386 &lt;211> 9 &lt;212&gt; PRT <213>Artificial Sequence&lt;220> &lt;223>Synthetic HLA-A2 Specific CTL Epitope Bit (181-189 aa of TAL6) &lt;400&gt; 13

Val lie Asn Gly Val Leu Gly Gly lie 1 5

&lt;210> 14 &lt;211> 9 &lt;212&gt; PRT &lt; 213 &gt; artificial sequence &lt;220 &lt; 223 &gt; 223 &gt; synthetic HLA-A24 specific CTL epitope (2-10 aa of TAL6) &lt;400&gt; 14

Cys Tyr Gly Lys Cys Ala Arg Cys lie 1 5 &lt;210> 15 &lt;211&gt; 9 &lt;212&gt; PRT &lt; 213 &gt; 213 &gt; artificial sequence &lt;220 &lt; 223 &gt; 223 > synthetic HLA-A24 specific CTL antigen table Bit (12-20 aa of TAL6) &lt;400&gt; 15

His Ser Leu Val Gly Leu Ala Leu Leu 1 5 &lt;210&gt; 16 &lt;211> 10 &lt;212> PRT &lt;213>Artificial Sequence 201204386 &lt;220> &lt;223>Synthetic HLA-A24 Specific CTL Antigen Epitope (28-36 aa of TAL6) &lt;400〉 16

Leu Tyr Phe Pro Asn Gly Glu Thr Lys Tyr 1 5 10 &lt;210&gt; 17 &lt;211&gt; 9 &lt;212&gt; PRT &lt;213>Artificial Sequence &lt;220&gt;&lt;223>Synthetic HLA-A24 Specific CTL Epitope (36-44 aa of TAL6) &lt;400&gt; 17

Lys Tyr Ala Ser Glu Asn His Leu Ser 1 5 &lt;210&gt; 18 &lt;211> 9 &lt;212> PRT &lt; 213 &gt; 213 &gt; artificial sequence &lt;220 &lt; 223 &gt; 223 &gt; synthetic HLA-A24 specific CTL epitope Bit (45-53 aa of TAL6) &lt;400> 18

Arg Phe Val Trp Phe Phe Ser Gly lie 1 5 &lt;210&gt; 19 &lt;211> 10 &lt;212> PRT &lt; 213 &gt; 213 &gt; artificial sequence &lt;220 &lt; 223 &gt; 223 &gt; synthetic HLA-A24 specific CTL epitope Bit (49-57 aa of TAL6) &lt;400> 19 201204386

Phe Phe Ser Gly lie Val Gly Gly Gly Leu 1 5 10 &lt;210&gt; 20 &lt;211> 9 &lt;212&gt; PRT &lt;213>artificial sequence &lt;220&gt;&lt;223>synthetic HLA-A24 specific CTL Epitope (105-113 aa of TAL6) &lt;400〉 20

Gly Tyr Cys Val lie Val Ala Ala Leu 1 5

&lt;210&gt; 21 &lt;211> 10 &lt;212&gt; PRT &lt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt;&lt;223&gt; synthetic HLA-A24 specific CTL epitope (131-140 aa of TAL6) &lt;400&gt; 21

Thr Phe Ala Ser Thr Glu Gly Gin Tyr Leu 1 5 10

&lt;210&gt; 22 &lt;211&gt; 9 &lt;212&gt; PRT &lt; 213 &gt; artificial sequence&lt;220&gt;&lt;223>synthetic HLA-A24 specific CTL epitope (138-147 aa of TAL6) &lt;;400> 22

Gin Tyr Leu Leu Asp Thr Ser Thr Trp 1 5 &lt;210> 23 201204386 &lt;211&gt; 9 &lt;212&gt; PRT &lt;213>Artificial Sequence &lt;220> &lt;223>Synthetic HLA-A24 Specific CTL Antigen Epitope (157-165 aa of TAL6) &lt;400&gt; 23

Glu Trp Asn Val Ser Leu Phe Ser lie 1 5 &lt;210&gt; 24 &lt;211> 14 &lt;212> PRT &lt;2]3&gt;artificial sequence &lt;220&gt;&lt;223>synthetic T helper cell stimulation fragment &lt;223&gt;;400〉 24

Gin Tyr lie Lys Ala Asn Ser Lys Phe lie Gly lie Thr Glu 1 5 10 &lt;210> 25 &lt;211&gt; 10 &lt;212> PRT &lt;213>artificial sequence &lt;220> &lt;223>Synthesis T assist Cell stimulation fragment &lt;400> 25

Ala Lys Phe Val Ala Ala Trp Thr Leu Lys 1 5 10 &lt;210&gt; 26 &lt;211&gt; 17 &lt;212> PRT &lt;213>artificial sequence 201204386 &lt;220> &lt;223>synthetic endoplasmic reticulum target Sequence &lt;400〉 26

Met Arg Tyr Met lie Leu Gly Leu Leu Ala Leu Ala Ala Val Cys Ser Ala 15 10 15 &lt;210&gt; 27 &lt;211&gt; 16 &lt;212> PRT &lt;213>artificial sequence &lt;220〉

&lt;223>Synthesized endoplasmic reticulum target sequence &lt;400〉 27

Arg Tyr Met lie Leu Gly Leu Leu Ala Leu Ala Ala Val Cys Ser Ala 15 10 15 &lt;210> 28 &lt;211&gt; 17 &lt;212&gt; PRT &lt;213>artificial sequence &lt;220> &lt;223&gt; Endoplasmic reticulum target sequence

&lt;400&gt; 28

Met Arg Ala Ala Gly lie Gly lie Leu Thr Val Ala Ala Ala Ala Ala Gly 15 10 15 &lt;210> 29 &lt;211> 17 &lt;212> PRT &lt;213>artificial sequence &lt;220> &lt;223>Synthesis Endoplasmic reticulum target sequence &lt;400〉 29 201204386

Met Ala Gly lie Leu Gly Phe Val Phe Thr Leu Ala Ala Ala Ala Ala Gly 1 5 10 15 &lt;210&gt; 30 &lt;211&gt; 202 &lt;212&gt; PRT &lt;213>human &lt;400&gt; 30

Met Cys Tyr Gly Lys Cys Ala Arg Cys He Gly His Ser Leu Val Gly 15 10 15

Leu Ala Leu Leu Cys lie Ala Ala Asn lie Leu Leu Tyr Phe Pro Asn 20 25 30

Gly Glu Thr Lys Tyr Ala Ser Glu Asn His Leu Ser Arg Phe Val Trp 35 40 45

Phe Phe Ser Gly lie Val Gly Gly Gly Leu Leu Met Leu Leu Pro Ala 50 55 60

Phe Val Phe lie Gly Leu Glu Gin Asp Asp Cys Cys Gly Cys Cys Gly 65 70 75 80

His Glu Asn Cys Gly Lys Arg Cys Ala Met Leu Ser Ser Val Leu Ala 85 90 95

Ala Leu He Gly lie Ala Gly Ser Gly Tyr Cys Val lie Val Ala Ala 100 105 110

Leu Gly Leu Ala Glu Gly Pro Leu Cys Leu Asp Ser Leu Gly Gin Trp 115 120 125

Asn Tyr Thr Phe Ala Ser Thr Glu Gly Gin Tyr Leu Leu Asp Thr Ser 130 135 140

Thr Trp Ser Glu Cys Thr Glu Pro Lys His lie Val Glu Trp Asn Val 145 150 155 160

Ser Leu Phe Ser lie Leu Leu Ala Leu Gly Gly lie Glu Phe lie Leu 165 170 175

Cys Leu lie Gin Val lie Asn Gly Val Leu Gly Gly lie Cys Gly Phe 180 185 190

Cys Cys Ser His Gin Gin Gin Tyr Asp Cys 195 200 &lt;210> 31 &lt;211> 9 &lt;212> PRT &lt;213>Artificial Sequence 10 201204386 &lt;220> &lt;223>Synthetic HLA-A2 Specificity CTL epitope (53-6 of TAL6) aa) &lt;400> 31 lie Val Gly Gly Gly Leu Leu Met Leu 1 5 &lt;210> 32 &lt;211&gt; 9 &lt;212> PRT <213> artificial sequence &lt;;220〉

&lt;223> Synthetic HLA-A2-specific CTL epitope (161-169 aa of TAL6) &lt;400&gt; 32

Ser Leu Phe Ser lie Leu Leu Ala Leu 1 5 &lt;210> 33 &lt;211> 9 &lt;212&gt; PRT &lt;213>Artificial Sequence &lt;220> &lt;223>Synthetic HLA-A2 Specific CTL Epitope Bit (177-185 aa of TAL6) &lt;400> 33

Cys Leu lie Gin Val lie Asn Gly Val 1 5 &lt;210> 34 &lt;211&gt; 12 &lt;212> PRT &lt;213> artificial sequence &lt;220> &lt;223>synthetic PADRE peptide 201204386 &lt;400&gt;

Ala Lys Phe Val Ala Ala Trp Thr Leu Lys Ala Ala 1 5 10 &lt;210&gt; 35 &lt;211&gt; 9 &lt;212&gt; PRT &lt;213>Artificial Sequence &lt;220&gt;&lt;223>Synthetic EBV-derived HLA-A2-specific epitopes &lt;400> 35

Gly Leu Cys Thr Leu Val Ala Met Leu 1 5 &lt;210&gt; 36 &lt;211> 12 &lt;212&gt; PRT &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt;223 Synthetic EBV-derived HLA-A2- Specific epitopes &lt;400&gt; 36

Gly Leu Cys Thr Leu Val Ala Met Leu Gly Leu Cys 1 5 10 &lt;210&gt; 37 &lt;211> 9 &lt;212> PRT &lt;2〗 3&gt; Artificial Sequence &lt;220&gt;&lt;223>Synthetic EBV- Derived HLA-A2-specific epitopes &lt;400> 37

Thr Tyr Gly Pro Val Phe Met Cys Leu 1 5 12 201204386 &lt;210&gt; 38 &lt;211> 12 &lt;212&gt; PRT &lt;213&gt;Artificial Sequence&lt;220&gt;&lt;223&gt;&gt;223>Synthetic EBV-derived HLA- A2-specific epitopes &lt;400&gt; 38

Thr Tyr Gly Pro Val Phe Met Cys Leu Thr Tyr Gly 1 5 10

&lt;210>39 &lt;211&gt; 9 &lt;212&gt; PRT &lt; 213 &gt; artificial sequence &lt;220 &lt; 223 &gt; 223 &gt; synthetic HLA-A24 specific CTL epitope (22-30 aa of TAL6) &lt;400&gt; 39 lie Ala Ala Asn lie Leu Leu Tyr Phe 1 5 &lt;210> 40 &lt;21]&gt; 9 &lt;212&gt; PRT &lt;213>artificial sequence &lt;220> &lt;223>Synthetic ΗΙΛ-Α24 Specific CTL epitope (131-139 aa of TAL6) &lt;400> 40

Thr Phe Ala Ser Thr Glu Gly Gin Tyr 1 5 &lt;210&gt; 41 &lt;211> 9 &lt;212> PRT &lt;213> Artificial sequence 13 201204386 &lt;220> &lt;223>Synthetic HLA-A24 specific CTL Epitope (155-163 aa of TAL6) &lt;400&gt; 41 lie Val Glu Trp Asn Val Ser Leu Phe 1 5 &lt;210&gt; 42 &lt;211&gt; 10 &lt;212&gt; PRT &lt;2]3&gt;&lt;220>&lt;223> Synthetic HLA-A24-specific CTL epitope (157-166 aa of TAL6) φ &lt;400&gt; 42

Glu Trp Asn Val Ser Leu Phe Ser lie Leu 1 5 10 &lt;210&gt; 43 &lt;211&gt; 9 &lt;212&gt; PRT &lt;213>artificial sequence &lt;220〉

&lt;223> Synthetic HLA-A24-specific CTL epitope (170-178 aa of TAL6) &lt;400> 43

Gly Gly lie Glu Phe lie Leu Cys Leu 1 5 &lt;210&gt; 44 &lt;211&gt; 10 &lt;212> PRT &lt;213&gt; Artificial sequence &lt;220&gt;&lt;223&gt;&gt;223&gt; Synthetic HLA-A24 specific CTL antigen table Bit (170-179 aa of TAL6) 14 201204386 &lt;400&gt; 44

Gly Gly lie Glu Phe lie Leu Cys Leu lie 1 5 10 &lt;210&gt; 45 &lt;211&gt; 10 &lt;212> PRT &lt;213>artificial sequence &lt;220&gt;&lt;223>Synthetic HLA-A24 specific CTL Epitope (154-163 aa of TAL6) &lt;400&gt; 45

His lie Val Glu Trp Asn Val Ser Leu Phe 10 &lt;210&gt; 46 &lt;211&gt; 8 &lt;212> PRT &lt;2]3&gt;artificial sequence&lt;220&gt;&lt;223&gt;&gt;223 derived from ovalbumin synthetic peptide Fragment &lt;400〉 46

Ser lie lie Asn Phe Glu Lys Leu &lt;210&gt; 47 &lt;211> 9 &lt;212> PRT &lt; 213 &gt; 213 &gt; artificial sequence &lt;220 &lt; 223 &lt; 223 &gt; 223 &gt; 223 &gt; synthetic peptide fragment derived from influenza virus M protein &lt;400&gt; 47

Gly lie Leu Gly Phe Val Phe Thr Leu 1 5 15

Claims (1)

201204386 VII. Patent Application Range: 1. An isolated immunopeptide comprising a T cell epitope derived from a tumor associated antigen L6 (TAL6) wherein the immunopeptide has a length of up to 50 amino acids. 2. The isolated immunopeptide according to claim 1 of the patent application, wherein the T cell epitope is specific for HLA-A2. 3. The isolated immunopeptide according to claim 2, wherein the tau cell epitope has a chromosome selected from CIGHSLVGL (SEQ ID ΝΟ: 1), SLVGLALLC (SEQ ID NO: 2), ALLCIAANI (SEQ ID NO) :3), # LLMLLPAFV (SEQ ID NO: 4), MLLPAFVFI (SEQ ID NO: 5), AMLSSVLAA (SEQ ID NO: 6) 'MLSSVLAAL (SEQ ID NO: 7), SVLAALIGI (SEQ ID NO: 8), a group consisting of GLAEGPLCL (SEQ ID NO: 9), HIVEWNVSL (SEQ ID NO: 10), SILLALGGI (SEQ ID NO: 1 1), ALGGIIFIL (SEQ ID NO: 12) or VINGVLGGI (SEQ ID NO: 13) Amino acid sequence. 4. The isolated immunopeptide according to claim 1 of the patent application, wherein the T cell epitope is specific for HLA-A24. ® 5. The isolated immunopeptide according to claim 4, wherein the T cell epitope has a selected from the group consisting of CYGKCARCI (SEQ ID NO: 14), HSLVGLALL (SEQ ID NO: 15) &gt; LYFPNGETKY (SEQ ID NO: 16) 'KYASENHLS (SEQ ID NO: 17) 'RFVWFFSGI (SEQ ID NO: 18), FFSGIVGGGL (SEQ ID NO: 19), GYCVIVAAL (SEQ ID NO: 20) ^ TFASTEGQYL (SEQ ID NO: 21) &gt; The amino acid sequence of the group consisting of QYLLDTSTW (SEQ ID NO: 22) and EWNVSLFSI (SEQ ID 26 201204386 NO: 23). 6. According to the patented fine 1 of the isolated immunopeptide, the step further comprises an endoplasmic reticulum target fragment. 7. According to the application of the exclusive immunosuppressive peptide of the first item, the step further comprises a T helper cell stimulating fragment. 8. According to the single immunopeptide of claim 7 of the special fiber, the τ helper cell stimulating fragment has the amino acid sequence of qYIKANSKFIGITE (SEQ ID N〇: 24) or 0 AKFVAAWTLK (SEQ ID NO: 25). . An immunological composition comprising an immunopeptide according to item 1 of the patent application and a pharmaceutically acceptable carrier. 10. The immunological composition according to claim 9 of the patent application, which further comprises an adjuvant. A method of treating cancer comprising administering an effective amount of an immunological composition according to claim 9 of the patent application to an individual in need thereof. Φ 12. The method of claim 11, wherein the individual has lung cancer, breast cancer, colitis or ovarian cancer. 13. A method for enhancing an immune response against TAL6 comprising administering an effective amount of an immunological composition according to claim 9 of the patent application to an individual in need thereof. An antibody that specifically binds to have an antibody selected from the group consisting of CIGHSLVGL (SEQ ID NO: 1), SLVGLALLC (SEQ ID NO: 2), ALLCIAANI (SEQ ID N〇: 3), LLMLLPAFV (SEQ ID NO: 4), MLLPAFVFI (SEQ ID NO: 5) ^ AMLSSVLAA (SEQ ID NO: 6) 'MLSSVLAAL (SEQ ID 27 201204386 NO: 7) 'SVLAALIGI (SEQ ID NO: 8) &gt; GLAEGPLCL (SEQ ID NO: 9)' HIVEWNVSL ( SEQ ID NO: 10) 'SILLALGGI (SEQ ID NO. l 1), ALGGIIFIL (SEQ ID NO: 12), VINGVLGGI (SEQ ID NO: 13), CYGKCARCI (SEQ ID NO: 14), HSLVGLALL (SEQ ID NO: 15) 'LYFPNGETKY (SEQ ID NO: 16) 'KYASENHLS (SEQ ID NO: 17), RFVWFFSGI (SEQ ID NO: 18), FFSGIVGGGL (SEQ ID NO: 19) 'GYCVIVAAL (SEQ ID NO: 20), TFASTEGQYL ( TAL6 fragment of the amino acid sequence of the group consisting of SEQ ID NO: 21), QYLLDTSTW (SEQ ID NO: 22) and EWNVSLFSI (SEQ ID NO: 23). # 15. 16. 17. An isolated nucleic acid encoding an immunopeptide according to the scope of the patent application. And another immune composition, which is included for performance according to the scope of the patent application! An expression carrier for an immunopeptide, and a pharmaceutically acceptable carrier. According to the application of the 16th item of the immune composition, the further steps include