TW201211250A - VANGL1 peptides and vaccines including the same - Google Patents

Abstract

The present invention provides isolated peptides or immunogenic fragments derived from SEQ ID NO: 69 that bind to an HLA antigen and induce cytotoxic T lymphocytes (CTL). The peptides may include one of the afore-mentioned amino acid sequences with or without the substitution, deletion, or addition of one, two, or several amino acids sequences. The present invention also provides pharmaceutical compositions containing such peptides. The peptides of this invention find utility in the treatment of cancer.

Description

201211250 VI. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention relates to the field of biological sciences, and more particularly to the field of cancer treatment. In particular, the present invention relates to a novel peptide which is very effective as a cancer vaccine and a drug for treating and avoiding tumors. [Prior Art] It has been confirmed that CD8-positive cells are toxic to the tumor-associated antigen (tumor) constructed on the main histocompatibility antigen complex Ua j〇r hist() cQmpatibi ii ty complex, MHC) class丨 molecule. -Associated antigens, TAAs) are epitope-determining peptides, and then kill tumor cells. Since the discovery of the melanomama antigen (MAGE) family as the first example of tumor-associated antigens, many other tumor-associated antigens have been discovered by immunological methods (NpLs i, 2). Some tumor-associated antigens are currently used as immunotherapeutic targets during clinical development. Suitable tumor-associated antigenic systems are essential for cancer cell proliferation and survival. The use of such tumor-associated antigens as immunotherapeutic targets minimizes the risk of cancer escapes that are widely described, while cancer cell immune escape is the result of therapeutic screening for immune screening, due to tumor-associated antigens. Delete, mutate or down regulate. Therefore, the identification of new tumor-associated antigens that can induce an effective and specific anti-tumor immune response has become the basis for the further development of vaccinati (10) strategies in various forms of cancer and the basis of clinical research for 201211250 ( NPLs3-1〇h has so far reported many clinical trials using these tumor-associated antigen-derived peptides. Unfortunately, many current cancer vaccine trials have shown low objective response rates (objective respQnse (NPLs U-13). Maintaining new tumor-associated antigens = = need for therapeutic targets. ~ A fruit fly gene called Van Gogh (Vang) was first identified as the appearance of fruit flies with abnormal small eyes, legs and bristles. Source of the responsible mutation (NPL 14). Gene expression profiling using a gene-wide cDNA microarray containing 23,040 genes, followed by identification of a homolog of the Vang gene, Vang-like 1 (VANGL1) For some of the cancer cells, one of the novel molecules is up-regulated, cancer cells such as hepatocellular carcinoma, pancreas and bladder cancer (NPL) Analysis of the performance of 6 adult normal tissues confirmed that VANGL1 transcript was specifically detected in the testis and ovary. In addition, the downward regulation of siRNA or antisense VANGL1 resulted in VANGL1 Inhibition of cell growth in liver cancer cells (npl 16, PTL1). In summary, these data suggest that VANGL1 may be a suitable target for cancer immunotherapy procedures, especially in patients with VANGL1 tumors. [Citations] Patent Literature (Patent) [PTL 1] WO 03/027322 Non Patent Literature 201211250 [NPL 1] Boon T, Int J Cancer 1993, 54(2): 177-80 [NPL 2] Boon T & van der Bruggen P, J Exp Med 1 996, 183(3): 725-9 [NPL 3 ] Harr is CC, J Natl Cancer Inst 1 996, 88(20): 1442-55 [NPL 4] Butterfield LH et al., Cancer Res 1999, 59(13): 3134-42 [NPL 5] Vissers JL et al., Cancer Res 1999, 59(21): 5554-9 [NPL 6] van der Burg SH et al., J Immunol 1996, 156 (9): 3308-14 [NPL 7] Tanaka F et al., Cancer Res 1 997, 57(20): 4465-8 [NPL 8] Fujie T et al., Int J Cance r 1 999, 80 (2 ): 169-72 [NPL 9] Kikuchi Metal., Int J Cancer 1 999, 81 (3): 459-66 [NPL 10] Oiso M et al., Int J Cancer 1 999, 81 (3): 387-94 [NPL 11] Belli F et a 1. , J Clin Oncol 2002, 20(20): 4169-80 [NPL 12] Coulie PG et al., Immunol Rev 2002, 188: 33- 42 [NPL 13] Rosenberg SA et al., Nat Med 2004, 1 0 ( 9 ): 201211250 909-15 [NPL 14] Taylor et al., Genetics. 1998: 150(1): 199-210 [NPL 15] Okabe et al 1., Cancer Res. 2001: 61(5): 2129-37 [NPL 16] Yagyu et al., Int J Oncol. 2002: 20(6): 1173-8 [Invention] At least part of the present invention Based on the discovery of suitable targets for immunotherapy. Since tumor-associated antigens (TAAs) are sometimes perceived by the immune system as "self" and therefore often have no immunogenicity, the discovery of suitable targets is extremely important. Identify VANGL1 (as described here in Sequence Identification Numbers: 68 and 69, and

The numbered AB057596, NM_〇〇1172411, NM-001 1 7241 2 or NM_1 38959 in GenBank has been identified as up-regulated in cancer, especially in bladder, breast, cervical, and cholangiocellular carcinomas. Carcinoma), sub-empty time w / . Ding s endometriosis (endometriosis), liver cancer, non-small cell lung cancer (n〇nsmaU "η iUng cancer (NSCLC), osteosarcoma, smear cancer, small cell lung cancer) Cell lung cancer (SCLC) and acute myelogenous leukemia (AML), the invention also has a ten-t focus on VANGL1 as a candidate for cancer/tumor immunotherapy, and more ' is the novel VANGL1 epitope peptide, which can be used as a suitable immunization/alpha therapeutic. 201211250 For this purpose, the present invention is at least in part related to the ability to induce a cytotoxic T lymphocyte specific to VANGL1. Confirmation of specific epitopes in the gene product of VANGL1. As discussed in more detail below, candidates from VANGL1 in combination with HLA (human leukocyte antigen)* 〇2〇1 were used. The peptide stimulates peripheral blood mononuclear cells (PBMCs) obtained from a health provider. Thereafter, a cytotoxic tau lymphocyte is established, which has an anti-against HLA that is pulsed by each candidate peptide. -A2 positive target cell cytotoxicity. These results demonstrate that these peptides are HLA-A2-restricted epitope peptides that induce strong and specific immune responses against cells expressing VANGL1. These results further show VANGL1 It is potently immunogenic and its epitope is an effective target for tumor immunotherapy. Therefore, it is an object of the present invention to provide an isolated peptide which binds to an HLA antigen and which comprises a VANGL1 sequence (SEQ ID NO: 69) or An immunologically active fragment thereof. These peptides are expected to have cytotoxic T lymphocyte evoked ability' and thus can be used to induce cytotoxic T lymphocytes in vitro, in vivo, or ex vivo or can be administered to a body To induce an immune response against cancer, examples of cancer include, but are not limited to, bladder cancer, breast cancer 'cervical cancer, cholangiocarcinoma, endometriosis, Liver cancer, non-small cell lung cancer, osteosarcoma, pancreatic cancer, small cell lung cancer and acute myeloid leukemia. The preferred peptides are nine peptides and ten peptides, and more preferred are the peptides of the nine peptides and the ten peptides. Identification numbers: amino acid sequences in 1 and 3 to 67. The peptide has a sequence identification number: the amino acid sequences in 1, 12 and 21 show strong cytotoxic T lymphocyte evoking ability and are therefore particularly favored. 201211250 The present invention also contemplates modified peptides having the amino acid sequence selected from the sequence identification numbers: 1 and 3 to 67 in which one, two or more amino acids are substituted, deleted, inserted or added As long as the modified peptide maintains the essential cytotoxic T lymphocyte inducing ability and HLA binding ability which are essential for the initial unmodified peptide. The invention further encompasses isolated polynucleic acids encoding any of the peptides of the invention. These polynucleotides can be used to induce or prepare antigen-presenting cells having the ability to induce cytotoxic T lymphocytes. Like the aforementioned peptide of the present invention, such antigen-presenting cells can be administered to a body to induce an immune response against cancer. When administered to a body, the peptide of the present invention is expressed on the surface of the antigen-presenting cell to induce separation. The peptide is the target of the cell-toxic tau lymphocytes. Accordingly, it is an object of the present invention to provide agents and/or compositions comprising or incorporating any of the peptides or polynucleotides of the present invention for use in inducing cytotoxic sputum lymphocytes. Such agents and/or compositions can be used for the treatment and/or prevention of primary cancer or metastasis or recurrence after surgery. The cancer case considered in the present invention includes, but is not limited to, bladder cancer, breast cancer, cervical cancer, ||tuber cell carcinoma, endometriosis, liver cancer, non-, laparoscopic lung cancer, osteosarcoma, pancreas Dirty cancer, small cell lung cancer and acute myeloid leukemia. Further preferred object of the present invention is to provide a pharmaceutical composition or agent which comprises or is formulated for the treatment and/or prophylaxis of primary cancer or metastasis or post-operative recurrence of any peptide or polynucleotide of the present invention. . In addition to or in place of the peptide or polynucleotide of the present invention, the pharmaceutical agent and/or composition of the present invention may comprise an antigen presenting cell or a small exocytosis presenting any of the present invention 8 201211250 The body is the active ingredient. The peptide or polynucleotide of the present invention can be used to induce an antigen presenting cell which exhibits a complex of an HLA antigen and a peptide of the present invention on its surface, for example, 'by presenting an antigen from one body to the present invention and the present invention The peptide is contacted or a polynucleotide encoding a peptide of the present invention is introduced into an antigen-presenting cell. Such antigen-presenting cells have high cytotoxic T-thrombophore-inducing ability against the target peptide and are therefore effective for cancer immunotherapy. Accordingly, the present invention includes a method of inducing an antigen-presenting cell having a cytotoxic T lymphocyte-inducing ability and an antigen-presenting cell obtained by the method. A still further object of the present invention is to provide a method of inducing cytotoxic T lymphocytes. Such a method comprises the steps of co-cultivating CD8-positive cells with antigen-presenting cells or exosome expressing the peptide of the present invention on its surface. 'Or a step of introducing a gene comprising a polynucleotide encoding a tau cell receptor (TCR) subunit polypeptide that binds to a peptide of the present invention. The cytotoxic T lymphocytes obtained by this method can be used in cancer, more particularly bladder cancer, breast cancer, cervical cancer, cholangiocarcinoma, endometriosis, liver cancer, non-small cell lung cancer, osteosarcoma, Provides utility in the treatment and/or avoidance of pancreatic cancer, small cell lung cancer, and acute myeloid leukemia. Therefore, still another object of the present invention is to provide a cytotoxic T lymphocyte obtained by the method of the present invention. Still another object of the present invention is to provide a method for inducing an immune response against cancer in a subject in need thereof. This method comprises administering a polynucleotide comprising a VANGL1 polymorphic, encoding a VANGL1 polypeptide, and exhibiting a multi-winning VANGL1 The antigen of the peptide presents the step of a composition of cells or exosome. 201211250 The applicability of the present invention extends to any of the diseases relating to or caused by over-expression of VANGL1, such as 2 bU, including, but not limited to, bladder cancer, breast cancer, cervical cancer, and sputum- Cholecystosis, endometriosis, liver cancer, non-small cell lung cancer, bone help, convulsions of pancreatic cancer, small cell lung cancer and acute myeloid leukemia. It is to be understood that the description of the present invention is not limited to the invention or other alternative embodiments of the present invention. In addition to the above, other objects and features of the present invention will become more fully apparent. However, it is to be understood that the foregoing description of the invention and the claims In particular, the present invention is described in the above description, and is not to be construed as limiting the invention. Various modifications and applications can be made by those skilled in the art without departing from the spirit and scope of the invention, as described in the scope of the claims. The other aspects, features, advantages and advantages of the present invention are apparent from the following description of the specific embodiments of the invention. Such objectives, features, advantages and advantages are apparent from the foregoing description of the accompanying examples, the drawings, the drawings, and all of the claims. [Embodiment] Further to the above summary, an object of the present invention is to provide 10 201211250 [1] an isolated peptide having cytotoxic tau lymphocyte inducing ability, wherein the peptide is composed of VANGL1 The amino acid sequence or an immunologically active fragment thereof. [2] The isolated peptide according to [1], wherein the peptide comprises an amino acid sequence, and the group consisting of free sequence identification numbers: 1, 12 and 21. [3] an isolated peptide comprising an amino acid sequence in which 1, 2 or several amino acids are substituted, deleted, inserted and/or added to the free sequence identification number: 1, 12 and Amino acid sequence of a group consisting of 21, and wherein the peptide has cytotoxic a lymphocyte evoking ability. [4] The isolated peptide according to any one of [1] to [3] wherein the peptide binds to a human leukocyte antigen. [5] The isolated peptide according to [4], wherein the human leukocyte tissue antigen is a human leukocyte antigen - Α2. [6] The peptide according to [5], wherein the peptide has the following characteristics - or both: (a) an amino acid selected from the group consisting of: 1, 12 and 21 The second amino acid of the N-terminus of the sequence is a group consisting of leucine and methionine; and (b) an amine of the group consisting of: 1, 12 and 21 The C-terminal amino acid of the acid sequence is a group consisting of free proline and leucine. [7] The isolated peptide according to any one of [1] to [6] wherein the peptide is a nine peptide or a ten peptide. 201211250 [8] An isolated polynucleotide which encodes the isolated peptide according to any one of [丨] to [7]. [9] A composition for inducing a cytotoxic lymphosphere, wherein the composition comprises one or more of the peptides according to any one of [丨] to [7], or one or more such as [ 8] the polynucleotide described. [10] A pharmaceutical composition for the treatment and/or prevention of cancer, and/or its avoidance of recurrence after surgery, wherein the composition comprises one or more of any one of [1] to [7] The peptide, or one or more of the polynucleotides as described in [8]. [11] The pharmaceutical composition according to [1], wherein the composition is formulated for administration to a human, and the human leukocyte tissue antigen is human leukocyte antigen-Α2. [12] A method for inducing an antigen-presenting cell having a cytotoxic lymphocyte-inducing ability, comprising the steps of: selecting a group consisting of: (a) in vitro, ex vivo or in vivo, presenting an antigen to cells and a peptide contact as described in any one of [1] to [7], and (b) introducing a polynucleotide encoding the peptide according to any one of [1] to [7] An antigen presents a cell. [1 3 ] A method for inducing a cytotoxic lytic lymphocyte, comprising the steps of: selecting a group consisting of: (a) co-culturing a CD8-positive tau cell with an antigen-presenting cell, the antigen-presenting cell expressing a human A complex of a white blood cell tissue antigen and a peptide as described in any one of [1] to [7] on the surface; 12 201211250 (b) co-culture of CD8-positive tau cells with exogenous corpuscles, exosome Characterizing a complex of a human leukocyte tissue antigen with a victory as described in any one of [丨]裘 [7], and (c) including a multi-peptide encoding a single cell receptor subunit The gene of the polynucleoside i is introduced into a T cell which binds to the peptide described in any one of [1] to [7]. [14] An isolated antigen-presenting cell which exhibits a complex of a human leukocyte antigen and a peptide as described in any one of [1] to [7] on its surface. [1] The antigen according to [14] presents a cell which is induced by the method as described in [i 2 ]. [16] An isolated cytotoxic tau lymphocyte, which is characterized by a peptide as described in any one of [i] to [7]. [17] The cytotoxic T lymphocyte according to [16], which is induced by the method as described in [13]. [18] - a method for inducing an immune response in a primary cancer in an individual', the method comprising a step of administering a composition of the individual, the composition comprising any one of [1] to [7] The peptide, an immunologically active fragment thereof, or a polynucleotide encoding the peptide or one of the fragments. [19] An antibody or an immunologically active fragment thereof, which is a peptide according to any one of [A] to [7]. [20] A vector comprising a nucleotide sequence encoding the peptide according to any one of [1] to [7]. [21] A host cell which is transfected or transfected with one of the expression vectors 13 201211250 as described in [2 0 ]. [22] A diagnostic kit comprising the peptide according to any one of [1] to [7], the nucleotide according to [8] or the antibody according to [19]. [23] The isolated peptide according to any one of [1] to [7], which is a group consisting of free sequence identification numbers: 1, 12 and 21. Or In another embodiment, the invention also provides the following peptides and their uses. [1] an isolated peptide having cytotoxic T lymphocyte-inducing ability 'where the peptide is composed of an amino acid sequence of VANGL1 or an immunologically active fragment thereof' or an isolated peptide, A cytotoxic T lymphocyte-inducing ability, wherein the peptide comprises an amino acid sequence of an immunologically active fragment of a peptide consisting of the amino acid sequence of the sequence number: 6 9 or an amine derived from the immunologically active fragment The composition of the base acid sequence. [2] The isolated peptide according to [1], wherein the peptide comprises a group consisting of an amino acid sequence and a free sequence identification number: 1, 3 to 67. [3] The isolated peptide according to [1] or [2], wherein 1, 2 or a plurality of amino acids are substituted, inserted, deleted or added to produce a repaired peptide' The cytotoxic T lymphocyte evoked ability of the original peptide. [4] The isolated peptide according to [3], wherein in the background of the human leukocyte antigen-A 2, the at least one substitution is selected from the group consisting of: (a) from the N-terminus The two amino acids are a group consisting of free leucine and methionine; and 14 201211250 m (b) C-terminal amino acid is a group consisting of free proline and leucine . [5] The isolated peptide according to any one of [1] to [4], wherein the sinensis is a nine-win or a ten-win. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the embodiments of the present invention, the preferred methods, components and materials are now described. However, it is to be understood that the description of the materials and methods of the present invention is for illustrative purposes only and is not intended to be limiting. It is to be noted that the present invention is not limited to the particular size, shape, size, materials, methodology, steps, etc. described herein, such as those described herein, which can be modified in accordance with conventional experimentation and/or optimization. In addition, the terminology used in the context of the invention is intended to be limited to the scope of the invention, and is not intended to limit the scope of the invention. The publications, patents or patent applications mentioned in this specification are hereby expressly incorporated by reference in their entirety. However, this is not to be construed as an admission that the invention I. Definitions The words used herein — — this, mean “at least — unless otherwise expressly stated. Used in relation to a substance (eg, peptide, antibody, polynucleotide, etc.) 35/isolated and "purified, meaning, means that the substance is substantially absent 15 201211250 at least one may be additionally included in the natural source Substance. Thus, the isolated or purified peptide means that the peptide is substantially free of cellular material, such as carbohydrates, lipids or other contaminating proteins from the cell or tissue source from which the peptide is derived, or when When synthesized, there is virtually no chemical precursor or other chemical. The phrase "substantially free of cellular material" includes the preparation of a peptide in which the peptide is separated from the cell composition of the cell, from which the cell is isolated or recombined. Thus, a peptide is substantially free of cellular material, including heterologous proteins having less than 30%, 20%, 10%, or 5% (by dry weight) (also referred to herein as a "contaminating protein"). Preparation of a multi-peptide. When the peptide is produced recombinantly, it is also preferred that there is substantially no medium, including a medium having a preparation volume of less than about 20% '10% or 5% of the peptide. Peptide preparation. When the peptide is produced by chemical synthesis, it is preferably substantially free of chemical precursors or other chemicals, including having less than about 30%, 20%, 10% or 5% of the peptide synthesis involved. Dry weight) peptide preparation for the preparation of a volume of chemical precursor or other chemical peptide. It can be shown that the particular peptide preparation comprises an isolated or purified trait, such as 'by dodecyl in protein preparation The appearance of a single band or colloidal analog after staining with sodium dodecy 1 sulfate (SDS)-polyacrylamide gel electrophoresis and Coomassie Brilliant Blue. In the above, the peptide of the present invention and the polynucleotide are isolated or purified. The terms "polypeptide", "peptide", and "protein" refer to the polymer of the amino acid residue. . This term applies to the amino acid 201211250 polymer 'in which one or more amino acid residues are modified residues or non-naturally occurring residues, such as artificial chemical mimics corresponding to naturally occurring amino acids' and Naturally occurring amino acid polymers. The term "oligopeptide", which is sometimes used in the specification, is used to mean the peptide of the present invention which is 20 residues or less, typically 15 residues or less, and is generally A residue between about 8 and about 11 residues, usually 9 or 10, is used herein. The term "amino acid" means naturally occurring and synthetic amino acid' and amino acid analogs. With amino acid mimetics, which act similarly to naturally occurring amino acids. The amino acid can be an L-amino acid or a D-amino acid. Naturally occurring amino acids are those encoded by the genetic code and those that are modified in the cell after translation (eg, hydroxypro 1 ine, 7*- ga-a-carboxyglutamate, and 0 - Ο-phosphoserine). The expression "amino acid analog," means a compound having the same basic chemical structure as the naturally occurring amino acid (an alpha carbon bonded to a hydrogen, a carboxyl group, an amine group and an R group), but with a Modified R-based or modified backbone (for example, homologous acid (h〇m〇serine) 'norleucine, methi〇nine, sulfoxide > Methionine methyl sulfonium. The phrase "amino acid mimetic, meaning a chemical compound which has a different structure than a general amino acid" but has a similar function. By IUPAC-IUB Biochemical Nomenclature

Comic ss i on suggests the commonly known three-letter symbol or one-letter symbol to indicate the amino acid herein. 17 201211250 The terms "gene", "polynucleic acid", "nucleic acid" and "nucleic acid" are used interchangeably herein and unless otherwise indicated, are similar to amino acids which are generally accepted by them. The single-letter code is used to indicate. The term "formula," and "comprising a product" as used herein, is meant to include a particular component in a particular amount, in combination with any product, either directly or indirectly, from a particular amount of a particular component. This term relates to a pharmaceutical group: 'intended to include a product' which includes - an active ingredient and an inert ingredient forming a carrier' and any product which is directly or indirectly derived from the combination, complexation or aggregation of any two or more components, or from a Or dissociation of multiple components, or other forms of reaction or interaction from one or more components. Accordingly, the combination 16 of the present invention comprises any composition prepared by mixing a carrier of the present invention with a pharmaceutically or physiologically acceptable carrier. The term "active ingredient" as used herein means a substance in an agent or a composition that is biologically or physiologically active. In particular, in the context of a pharmaceutical agent or composition, the phrase "active ingredient," means a substance which exhibits a pharmaceutical effect of a target. For example, if a pharmaceutical agent or composition is used in the treatment or avoidance of cancer, The active ingredient in the agent or composition may directly or indirectly cause a biological or physiological action on cancer cells and/or tissues. Preferably, this effect may include reducing or inhibiting cancer cell growth, damage or killing cancer cells and/or Or tissue, etc. In general, the indirect effect of the active ingredient is to induce cytotoxic tau cells to recognize or kill cancer cells. Before being formulated, "active ingredient" can also mean "bulk", " "Pharmaceutical product" or "technical product" or "the pharmaceutically acceptable carrier" as used herein. 18 201211250 A commercially acceptable carrier, meaning pharmaceutically or physiologically An acceptable material, composition, substance, compound or carrier, including but not limited to a liquid or solid filler, diluent, excipient, solvent or sleeve A material which is associated with stabilizing or transporting an active ingredient from one device or part of the body to another organ or part of the body. Some pharmaceutical agents or compositions of the invention provide a particular use as a vaccine. In the context of the present invention, the wording "Vaccine (also meant to be a consensus immunological composition)" means an agent or composition that has the function of improving, enhancing and/or inducing anti-tumor immunity by inoculation into an animal. Unless otherwise defined, The term "cancer," means a cancer that overexpresses the VANGL1 gene, examples of which include, but are not limited to, bladder cancer, breast cancer, cervical cancer, cholangiocarcinoma, endometriosis, liver cancer, non-small cell lung cancer, osteosarcoma , pancreatic cancer, small cell lung cancer and acute myeloid leukemia. Unless otherwise defined, this may be used interchangeably and unless otherwise specifically indicated by the terms "cytotoxic T lymphocytes," "cytotoxic sputum cells" and "CTL" to mean τ lymphocytes. Ethnicity, and unless otherwise indicated, 'sub-group of T lymphocytes is identifiable to non-self cells (eg, tumor cells 'cells infected with the virus) and induces these cells to die. Definition, the term "HLA-A2", meaning HLA-A2, which includes subtypes of 'subtypes' including but not limited to HLA-A*020 1, HLA-A*0202, HLA-A*0203, HLA -A*0204, HLA-A*0205, HLA-A wood 0206, HLA-A*0207, HLA-A*0210, HLA-A*0211, 19 201211250 HLA-A*0213, HLA-A*0216, HLA -A*0218, HLA-A*0219, HLA-A*0228 and HLA-A*0250. Unless otherwise defined, the term "set" used herein is used in relation to reagents and other materials. The kit includes microarrays, wafers, labels, etc. There is no intention to use the term "set" to limit specific combinations of reagents and/or materials. As used herein, in the context of a subject or patient, the phrase "the individual's (or patient's) HLA antigen is HLA-A2" means that the individual or patient has homozygously or heterogeneously bound ( Heterozygously) has the HLA A2 antigen gene as the major histocompatibility complex (MHC) class I molecule and the HLA-A2 antigen is expressed as an HLA antigen in the cells of the individual or patient. The scope of the methods and compositions of the invention provides for the use of "treatment" in cancer, a treatment being considered "effective" if it results in clinical advantages, such as a decrease in the expression of the VANGL1 gene, or cancer in an individual The size, prevalence, or reduction in metastatic potential. When treatment is provided prophylactically, "effective, means slowing or avoiding cancer formation, or avoiding or ameliorating the clinical symptoms of cancer. Validity is identified in any known method for the diagnosis or treatment of a particular tumor form. The scope of the methods and compositions of the present invention provides for the use of "avoidance" and "prevention" of cancer, and such terms are used interchangeably to mean any activity that reduces the burden of mortality or from disease. Mortality. Avoiding 20 201211250 Exemption and prevention can occur in “initial, second and third avoidance levels.” Early avoidance and prevention avoids the development of disease, @ avoidance and prevention of the second and third levels includes By restoring function and reducing disease-related complications, the purpose is to develop the disease and the emergence of symptoms and to reduce the prevention and prevention of the development of the established disease. Or, treatment or avoidance may include _, the prevention of disease treatment, It aims to slow down the severity of specific diseases, such as reducing the proliferation and metastasis of tumors. In the context of the present invention, the treatment of cancer And/or prevention, or, and/or avoidance of recurrence after surgery, includes any of the following steps, such as surgical removal of cancer cells, growth inhibition of cancerous cells, tumor regression or degeneration, slowing of cancer and induction of inhibition 'Reduction and inhibition of tumor degeneration and metastasis. Effective treatment and/or prevention of cancer reduces mortality and improves the prognosis of individuals with cancer, reduces the extent of cancer markers in the blood and slows down the symptoms associated with cancer. The reduction or amelioration of symptoms constitutes an effective treatment and/or prevention which includes 10%, 2%, 3% or more, or stabilizes the disease. In the context of the present invention, the term "antibody" means immunoglobulin and A fragment that specifically reacts with a selected protein or its peptide. An antibody can include a human antibody, a primate antibody, a chimeric antibody, a bispecific antibody, a humanized antibody, and other proteins or a fluorescent marker. Fusion of antibodies, and antibody fragments. In addition, the antibodies herein are used for maximum utility and include, in particular, intact monoclonal antibodies, multiple antibodies , a multispecific antibody (eg, a bispecific antibody) formed from at least two intact antibodies and an antibody sheet 21 201211250, as long as it has the desired biological activity. An "antibody," means all species (eg, IgA, IgD, IgE, IgG and igM) Unless otherwise specifically defined, 'all technical and scientific terms used herein are the same as commonly understood by those skilled in the art. 11. Peptide to prove the victorious effect from VANG L1 As an antigen recognized by cytotoxic thymocytes (CTLs), the peptide from VANGL1 (SEQ ID NO: 35) was analyzed to determine whether it is an HLA that normally encounters an HLA dual gene (a 11 e 1 e). (Human leukocyte antigen)-A2 restricted epitope (Date Y et al., Tissue Antigens 47: 93-1 01, 1996; Kondo A et al., J Immunol 155: 4307-12, 1995; Kubo RT Et a 1., J Immunol 152: 3913-24, 1994). Candidates for HLA-A2 binding peptides from VANGL1 were confirmed using information on their binding affinity to HLA-A2. Confirm the following candidate peptides: VANGL1-A02-9-194 (Serial Identification Number: 1) 'VANGL1-A02-9-162 (Serial Identification Number: 3), VANGL1-A02-9-187 (Serial Identification Number: 4) , VANGL1-A02-9-190 (sequence identification number: 5), VANGL1-A02-9-225 (sequence identification number: 6) ' VANGL1-A02-9-118 (sequence identification number: 7), VANGL1-A02- 9-120 (sequence identification number: 8), VANGL1-A02-9-474 (sequence identification number: 9), VANGL1-A02-9-183 (sequence identification number: 10) ' 22 201211250 VANGL1-A02-9-124 (Sequence identification number: VANGU-A02-9-235 (Sequence identification number: VANGU-A02-9-1 59 (sequence identification number: VANGL1-A02-9-458 (sequence identification number: VANGL1-A02-9-423 ( Serial identification number: VANGL1-A02-9-230 (Sequence identification number: VANGL1-A02-9-20 1 (sequence identification number: VANGL1-A02-9-451 (sequence identification number: VANGL1-A02-9-294 (sequence Identification number: VANGL1-A02-9-246 (Sequence identification number: VANGL1-A02-9-484 (sequence identification number: VANGL1-A02-9-216 (sequence identification number: VANGL1-A02-9-422 (sequence identification number) : VANGU-A02-9-181 (Sequence ID: VANGL1-A02-9-1 53 (Sequence ID: VANGL1-A02- 9-489 (Sequence Identification Number: VANGL1-A02-9-219 (Sequence Identification Number: VANGL1-A02-9-161 (Sequence Identification Number: VANGU-A02-9-229 (Serial Identification Number: VANGL1-A02-9- 499 (Sequence Identification Number: VANGL1-A02-9-1 55 (Sequence Identification Number: VANGU-A02-9-56 (Sequence Identification Number: VANGL1-A02-9-514 (Sequence Identification Number: VANGL1-A02-1 0- 188 (sequence identification number 11), 12), 13), 14), 15), 16), 17), 18), 19), 20) ' 21), 22) ' 23) ' 24) ' 25) ' 26) ' 27) , 28) ' 29) ' 30) , 31) , 32) , 33) ' 34 ) > 23 201211250 VANGU-AO2-10-189 (Sequence Identification Number: VANGL1-A02-10-110 ( Serial Identification Number: VANGL1-A02-10-151 (Sequence Identification Number: VANGU-A02-1 0-230 (Sequence Identification Number: VANGU-A02-1 0-245 (Sequence Identification Number: VANGL1-A02-1 0-1 24 (Sequence Identification Number: VANGL1-A02-1 0-481 (Sequence Identification Number: VANGL1-A02-10-161 (Sequence Identification Number: VANGL1-A02-1 0-293 (Sequence Identification Number: VANGL1-A02-1 0 -506 (Sequence Identification Number: VANGL1-A02-1 0-400 (Sequence Identification Number: VANGL1-A02-10-136 (Sequence Identification Number: VANGL1-A02-1 0- 1 22 (Sequence Identification) : VANGL1-A02-1 0-485 (Sequence Identification Number: VANGL1-A02-1 0-229 (Sequence Identification Number: VANGL1-A02-1 0-1 60 (Sequence Identification Number: VANGU-A0 2-10-112 ( Serial Identification Number: VANGU-A0 2-1 0-474 (Sequence Identification Number: VANGL1-A02-1 0- 1 55 (Sequence Identification Number: VANGL1-A02-1 0-232 (Sequence Identification Number: VANGL1-A02-1 0-422 (Sequence Identification Number: VANGL1-A02-1 0-183 (Sequence Identification Number: VANGL1-A02-1 0-1 53 (Sequence Identification Number: VANGL1-A02-1 0-450 (Serial Identification Number: 35) , 36), 37), 38), 39), 40), 41), 42), 43), 44), 45), 46), 47), 48), 49), 50), 51), 52 ), 53), 54), 55), 56), 57), 58), 24 201211250 VANGL1-A02-10-218 (sequence identification number: 59), VANGL1-A02-1 0-473 (sequence identification number: 60), VANGL A02-1 0-1 97 (sequence identification number: 61), VANGL1-A02-1 0-491 (sequence identification number: 62), VANGL1-A02-1 0-1 94 (sequence identification number: 63), VANGL Α 02-10-Π 8 (sequence identification number: 64), VANGL 卜 A02-1 0-1 04 (sequence identification number: 65), VANGL1-A02-1 0-266 (sequence identification number: 66) and VANGU-A02-10-246 (sequence identification number: 67). In addition, /'/7 κ/ίΓσ succeeded in establishing cytotoxic T by using each of the following teams~ peptides by stimulating sputum cells with dendritic hexa-', dendritic cel 1, DC Lymphocytes: VANGL1-A02-9-194 (sequence identification number: 1), VANGL1-A02-9-235 (sequence identification number: 12), and VANGL1-A02-9-484 (sequence identification number: 21). These established cytotoxic T lymphocytes showed strong and specialized resistance to lymphocyte activity in the cells of the target cells pulsed with the peptide alone. These results demonstrate that VANGL1 is an antigen recognized by cytotoxic thymocytes, and the peptide tested is the determinant peptide of VANGU restricted by HU_A2. Due to VANGL1 gene in cancer cells, such as bladder cancer, breast cancer, cervical cancer, tube II cell carcinoma, endometriosis, liver cancer, non-small cells 25 201211250 lung cancer, osteosarcoma pancreatic cancer, small cell lung cancer and acute Myeloid leukemia _ is overexpressed 'and not in most normal organs, so it is a good cancer immunotherapy target. Therefore, the present invention provides a nine-peptide (the peptide consists of nine amino acid residues) and a ten-peptide (a peptide consisting of ten amino acid residues) derived from the cytotoxic tau lymphocyte recognition epitope of VANGL1. Basic composition). Alternatively, the present invention provides an isolated peptide that binds to an HLA antigen and induces a cytotoxic T lymphocyte, wherein the peptide has an amino acid sequence as described in Sequence ID: 69 or an immunologically active sheet thereof. &. More specifically, in some embodiments, the invention provides a peptide having the amino acid sequence of the group consisting of 1 '12 and 21'. A software program available today, for example, on the Internet can be used, for example,

Parker KC ei a/., J Immun〇i 1994, 152(i): 1 63 75 those used to calculate / knife "" (7) between the various peptides and HU antigen binding affinity. For example, In Parker KC da/.,〗 Iinmun〇i 1994, 152(1): 163-75, with Kuzushima K B1〇〇d

2001, 98(6): 1872-81, Larsen MV et al. BMC

Bioinfooiatics. 2007; 8: 424, with Buus S et al. Tissue

The binding affinity to HLA antigens can be measured as described in Antigens'62:378-84'. A description of the method of measuring affinity, for example in J〇urnal 〇f

Immunological Methods, 1995, 185: 18, 19 〇 and pr〇tein Science' 2000' 9: 1838-1846. Therefore, such a software program can be used to select those fragments from VANGL1 which have a high binding affinity to the Hu antigen. The invention thus encompasses a peptide consisting of any fragment 26 201211250 from VANGU, which is confirmed to bind to HLA by such a known red form. Further, such a peptide may comprise a peptide consisting of a peptide of the VANGL1 sequence of the whole 4 νΛΜΓ田. The peptides of the present invention, particularly the nine wins and ten wins of the present invention, may have additional amino acid residues on the side as long as the peptide maintains its cytotoxic tau lymphocyte inducing ability. The specific additional amino acid residues may be composed of any kind of amino acid as long as they do not reduce the cytotoxic thymocyte inducing ability of the original peptide. Thus, the invention encompasses a peptide having a binding affinity for a HU antigen comprising a peptide derived from VANGL1. Such peptides, e.g., less than about 40 amino acids, are often less than about 2 amino acids, typically less than about 15 amino acids. In general, it is known that modification of one or more amino acids in a peptide does not affect the function of the peptide or, in some instances, even enhances the desired function of the original protein. In fact, modified peptides are known (ie, amino acids modified by substitution, deletion, insertion or addition of one, two or several amino acid residues to an original amino acid sequence) Composition) maintains the biological activity of the original peptide (Mark ei 3/., Proc Natl Acad Sci USA 1984, 81: 5662-6; Zoller and Smith, Nucleic Acids Res 1982, 10: 6487-500; Dalbadie-McFarland et al ., Proc Natl Acad Sci USA 1 982,79: 6409-1 3). Therefore, according to an embodiment of the present invention, the peptide having the cytotoxic T lymphocyte inducing ability of the present invention may comprise a peptide consisting of amino acid sequences selected from the sequence identification numbers: 1, 12 and 21, One or two or more amino acids are added and/or substituted. 27 201211250 Those skilled in the art will recognize that a single percentage change in a single amino acid or a whole amino acid sequence, ie addition, deletion, insertion and/or substitution to an amino acid sequence, results in preservation of the original amino acid. The nature of the branch; it is therefore meant to be a conservative substitution or a "conservative modification" in which a change in a protein results in a protein with a similar function. Representatives are well known in the art. Examples of the characteristics of amino acid branches are hydrophobic amino acids (A, I, L, M, F, P, W, Y, V), hydrophilic amino acids (R, d, N, C, E, Q, G, Η 'K, S, T) with a bond having the following common functional groups or characteristics: an aliphatic branch (G, Α, V, L, I, Ρ) ; - hydroxyl group-containing branch (s, τ, γ); branch containing sulfur atom (C, M); containing carboxylic acid and amine branch (d, N, E, Q); containing alkali branch (R, K, H); and containing aromatic branches (h, F, Y, W). In addition, the following eight groups each contain amino acids which are conservatively substituted with each other. 1) alanine (A), glycine (G); 2) aspartic acid (D), glutamic acid (E); 3) aspartame (N), glutamine (Q); 4) arginine (R), lysine (K); 5) isoleucine (I), leucine (L), methylthiobutyric acid (μ), proline (V); ) phenylalanine (F), tyrosine (Y), tryptophan (w); 7) serine (S), sulphate (T); and 8) cysteine (C), sulphur Butyric acid (M) (see, for example

Creighton, proteins 1984). 28 201211250 Such conservatively modified peptides are also considered to be peptides of the invention. However, the peptide of the present invention is not limited thereto, and may include a non-conservative modification as long as the modified peptide maintains the cytotoxic thymocyte stimulating ability of the original unmodified peptide. Furthermore, the modified peptide does not exclude polymorphic variants, interspecies homosexuals (interspecies h〇m〇l〇gues) and Vmgli alleles (alleles) cytotoxic τ lymphocytes induced Peptide. The amino acid residue can be inserted, substituted, deleted/and or added to the peptide of the present invention, or the amino acid residue can be deleted therefrom to achieve a higher binding affinity. In order to maintain the necessary cellular toxin-like lymphocyte evokability, it is preferred to modify (add, insert, delete/or replace) a small number (e.g., one, two or several) or a small percentage of amino acid. The phrase "several means 5 or fewer amino acids, for example 4 or 3 or less. The percentage of modified amino acid may be, 2% or less, for example, 15% or more. Less, even more preferably 1% or less, such as 1 to 5%. When used in immunotherapy, the peptide of the present invention is expressed on the surface of a cell or exosome, such as a complex accompanying an HLA antigen. Therefore, it is preferred to select a peptide which not only induces a cytotoxic tau lymphocyte but also has a high affinity for an HLA antibody. For this purpose, insertion, deletion and/or addition by substitution of an amino acid residue can be used. Modification of the peptide has produced a modified peptide with improved binding affinity. 27 The natural manifestation of the victory is due to the rule of the peptide sequence represented by '° α to HLA antigen (j Immunol 1994, 152: 3913; Immunogenetics 1995, 41: 178: JI Long (10) 01 l " 4' 155: 4307) It is known that 29 201211250 modifications based on this rule can be introduced into the immunogenic peptide of the present invention. For example, 'has high HLA -A2 binding affinity peptide has a tendency to have phenylalanine a second amino acid from the N-terminus substituted with tyrosine, methionine or tryptophan. Similarly, 'the C-terminal amino acid is phenylalanine, leucine, isoleucine, color Amino acid or methylthiobutyric acid substituted peptides can also be used favorably. Therefore, peptides having amino acid sequences selected from sequence numbers: 1, 12 and 21, wherein the amino acid sequence of the sequence number The second amino acid from the N-terminus of the acid sequence is substituted with a leucine or thioglycolic acid, with a peptide, and/or the C-terminal amino acid of the amino acid sequence of which the sequence number is 缬Amine acid or leucine substitution is contemplated by the present invention. Or 'in a peptide exhibiting high HLA-A2 binding affinity, it may be desirable to replace a second amino acid from the N-terminus with leucine or methyl sulfide. Butyric acid, or amino acid at the C-terminus, is valine or leucine. Therefore, peptides having the amino acid sequence selected from the sequence identification numbers: 1, 12 and 21, wherein the N-terminal The two amino acids are substituted with leucine or methionine, and/or the amino acid at the C-terminus is substituted with a linear acid or leucine. The inclusion of the substitution can introduce more than the terminal amino acid, but also the identification of the potential TCR position of the peptide. Some studies have confirmed that a peptide with an amino acid substitution can be equal to or better than the original 'eg CAP1 , p53 (mm. Her-2/neu (369-377) or gplOO (2 0 9 - 2 1 7 ) (Zaremba a厶 Cancer Res. 57, 4570-4577, 1997, T. Κ. Hoffmann et al. J Immunol. (2002); 1 68(3):1 338-47., S. 0. Dionne et al. Cancer Immunol immunother. (2003) 52: 199-206 and S. 0. Dionne et al. Cancer Immunology, Immunotherapy (2004) 30 201211250 53, 307-314) 〇

The invention also contemplates the addition of one, two or several amino acids to the N and/or c terminus of the peptide of the invention. The present invention also encompasses such modified peptides having high HU antigen binding affinity and maintaining cytotoxic T lymphocyte eliciting ability. For example, the present invention provides an isolated peptide having a length of less than 14, 13, 3, 11, or 10 amino acids having cytotoxic T lymphocyte evoking ability and including selection from the group consisting of Amino acid sequence: (i) an amino acid sequence in which 1, 2 or several amino acids are modified in the amino acid sequence of the group consisting of: 1 and 3 to 33' Wherein the peptide binds to the HLA antigen and induces a cytotoxic thymocyte, (ii) the amino acid sequence of (i), wherein the amino acid sequence has one or both of the following characteristics: (a) from the sequence The second amino acid at the n-terminus of the identification number is modified to leucine or guanidine thioglycolic acid; and (b) the C-terminal amino acid of this sequence number is modified to valine or leucine. In addition, the present invention also provides an isolated peptide having a length of less than 15, 14, 13, 12 or 11 amino acids having cytotoxic T lymphocyte evoking ability and including selection from the group consisting of Amino acid sequence: (i ') monoamino acid sequence, wherein 1, 2 or several amino acids are modified in an amino acid sequence of a group consisting of: 34 to 67, wherein The peptide binds to the HLA antigen and induces a cellular toxic T lymphocyte 31 201211250 sphere, and an amino acid sequence of (ii' )(i'), wherein the amino acid sequence has one or both of the following characteristics: 〃 (a The second amino acid from the N-terminus of the sequence identifier is modified to leucine and acesulfame; and (b) the C-terminal amino acid of the sequence identifier is modified to valine and Amino acid. When these peptides are brought into contact with antigen-presenting cells or introduced into antigen-presenting cells, 'the peptides are treated in antigen-presenting cells to present (丨), (i丨), (i') and (ii') peptides. On it. However, when the peptide sequence is identical to a portion of the amino acid sequence of an endogenous or exogenous protein having a different function, side effects such as autoimmune diseases and/or anti-specific substance allergy syndromes may be induced. Therefore, a homologous search can be performed first using the available database to avoid the case where the sequence of the peptide conforms to the amino acid sequence of other proteins. When more than one homologous search for a peptide different from the target peptide with one or two amino acids becomes clear, 'in order to increase its binding affinity to the HLA antigen, and/or increase its cytotoxic T lymphocyte evoked The ability to modify the target amino acid without any risk of side effects. Although a peptide having a high binding affinity for an HLA antigen as described above is expected to be a south potency 'but a candidate peptide selected according to the two-parent performance of the indication is further tested for cytotoxic T lymphocyte-inducing ability. which performed. The phrase "cytotoxic T lymphocyte-inducing ability" herein means the ability of a peptide to induce a cytotoxic tau lymphocytic 32 201211250 sphere when expressed on an antigen-presenting cell. In addition, 'the cytotoxic lytic lymphocyte-inducing ability "Including peptide-induced cytotoxic T lymphocyte activation, cytotoxic T lymphocyte proliferation, promotion of cytotoxic T lymphocyte decomposing target cells and increased ability to produce cytotoxic T lymphocytes IFN-r. The antigen of the human MHC antigen is present in cells (eg, B-lymphocytes, macrophages, and dendritic cells) or more specifically from dendritic cells of human peripheral blood mononuclear cells, and is mixed with CD8 positive cells after stimulation with peptides. And then measuring the IFN-γ produced and released by the cytotoxic T lymphocytes of the target cell to determine the cytotoxic T lymphocyte evoking ability. Such a reaction system can use an antigen that has been produced to express human HLA Genetically transformed animals (for example, in Ben Mohamed L, Krishnan R, Longmate J, Auge C, Low L, Primus J, Diamond DJ, Hum Immunol 2000, 61(8) 764-79, Related Articles, Books, Linkout Induction of CTL response by a minimal epitope vaccine in HLA A*0201/DR1 transgenic mice: dependence on HLA class II restricted T(H) response). For example, 51Cr radiation can be labeled Target cells, and can calculate cytotoxic activity from radioactivity released from the target cells. Or 'can be produced and released by cytotoxic T lymphocytes in the presence of antigen-presenting cells carrying immobilized peptides IFN-r' and using an anti-IFN-r monoclonal antibody to visualize the inhibitory region on the culture medium. The cytotoxic T lymphocyte evoked ability of the test peptide as described above was found to have a sequence identification number. The nine peptides or the ten peptides of those peptides of the 33 201211250 amino acid sequence proposed in 1, 12 and 21 show particularly high cytotoxic T lymphocyte evoking ability and high binding affinity to HLA antigen. Thus these peptides are exemplified as preferred embodiments of the invention. Furthermore, the results of the 'homology analysis demonstrate that such peptides are not associated with any other known person The peptides of the gene product have significant homology. When used in immunotherapy, this reduces the likelihood of an unknown or unwanted immune response. Therefore, also from this aspect, these peptides are for cancer patients. It is effective in causing immunity against VANGL1. Thus, preferred forms of the invention include amino acid sequences selected from the group consisting of: sequence number: 1, 12 and 21. In addition to the modifications of the peptides of the present invention discussed above, the peptides of the present invention can be linked to other peptides as long as the resulting peptides are maintained to maintain the essential cellular toxic T lymphocyte eliciting ability of the original peptide. And more preferably to maintain an essential HLA combination. Examples of other peptides include: a peptide of the invention or a cytotoxic T lymphocyte-inducing peptide derived from other tumor associated antigens. Linkers between peptides are well known in the art, for example AAY (PM Daftarian a/., J Trans Med 2007, 5:26) 'AAA' NKRK (RPM Sutmuller et al., J Immunol. 2000, 1 65: 7308-731 5) or K (S. Ota eia/., Can Res. 62, 1471-1476, KS Kawamura s/., J Immunol. 2002, 168: 5709-5715). For example, a non-VANGL1 tumor associated antigen peptide can also be used substantially simultaneously to increase the immune response via HLA class I and/or class II. It has been fairly confirmed that cancer cells can exhibit more than one tumor-associated gene. It is in the context of routine experimentation for those skilled in the art to determine whether a particular tumor-associated gene is expressed in a particular individual, and then includes HLA class I and/or class II binding peptides from the performance products of such genes. In the VANGL1 composition or vaccine of the invention. Examples of HLA class I and HLA class I Γ binding peptides are known to those skilled in the art (for example, see coulie, stem

Cells 13: 393-403' 1995), and can be used in the present invention in a similar manner to those disclosed herein. A multi-peptide comprising one or more VANGU peptides and one or more non-VANGL1 peptides, or a nucleic acid encoding such a multi-peptide, can be prepared by those skilled in the art in accordance with standard procedures for molecular biology. Such a linked peptide as described above means "polytope" herein. That is, two or more groups of potential immunogenic or immunoreactive stimulating peptides can be ligated to each other in a variety of arrangements (e.g., in a string or in partial overlap). Polyhedra (or nucleic acids encoding polyhedrons) can be administered in accordance with standard immunization procedures, for example, to animals to test the efficacy of polyhedra in stimulating &/or inducing an immune response. The triumph can be directly linked or via the use of a sequence located on the side to form a polyhedron, and the use of a polyhedron for a vaccine is well known in the art (see 'Thomson et al., Proc. Natl. Acad. Sci USA 92(13): 5845-5849, 1995; Gilbert et al.y Nature

Biotechnol. 15(12): 1280-1284, 1997; Thomson et al., J Immunol. 157(2): 822-826, 1996; Tarn et al J Exp Med. 171(1): 299-306, 1990) . Different numbers and combinations of polymorphs of epitopes were prepared and included for testing by cytotoxic T lymphocyte 35 201211250 and for increasing efficacy in immune responses. Further, the peptide of the present invention can be further linked to other substances as long as they maintain an essential cytotoxic tau lymphocyte inducing ability. Such materials include: peptides, lipids, sugars and sugar chains, acetyl groups, natural and synthetic polymers, and the like. The peptide may comprise modifications such as glycosylation, branched oxidation or phosphorylation as long as the modification does not impair the biological activity of the peptide as described herein. These types of modifications can be performed to grant additional functionality (e.g., target function and delivery function) or to stabilize multi-peptides. For example, in order to increase the stability of the multi-peptide by /.77 F/FO, it is known in the art to introduce a D-amino acid, an amino acid mimetic or an unnatural amino acid; this content is also suitable for the multi-win of the present invention. Peptide. It can be - some methods to analyze - the stability of multiple wins. For example, peptidase can be used with a variety of biological media, such as human plasma and serum, to test for stability (see, for example, 〇4)

Eur J Drug Metab Pharmacokin 1986, 11: 291-302). Furthermore, as mentioned above, in a modified peptide substituted, deleted or added by one, two or several amino acid residues, the same or higher than the original peptide can be screened or selected. Those active. The invention therefore also provides a method of screening or selecting a modified peptide having the same or higher activity as the original. For example, the method can include the steps of: a. replacing, deleting or adding at least one amino acid residue of the peptide of the present invention, b: determining the activity of the peptide, and selecting the same or higher than the C: selection compared to the original. Active peptide. The site/archaics may include MHC binding activity, antigen presenting cells, or cytotoxic activity. Here, the peptide of the present invention can also be described as "vangu peptide, or "VANGL1 polypeptide,". Preparation of Π I· VANGL1 peptide The peptide of the present invention can be prepared using well-known techniques. For example, a peptide can be prepared synthetically by recombinant DNA techniques or chemical synthesis. The peptide can be synthesized alone or as a longer multi-peptide comprising two or more peptides. The peptide can be isolated' to purify or isolate substantially no other naturally occurring host cell protein from its fragments or any other chemical. The peptide of the present invention may comprise modifications such as glycosylation, branched chain oxidation or phosphorylation which provide a biological activity which does not damage the original peptide. Other modifications include combinations of D-amino acids or other amino acid mimetics that can be used, for example, to increase the serum half-life of the peptide. The peptide of the present invention can be obtained by chemical synthesis according to the selected amino acid sequence. For example, general peptide synthesis methods suitable for this synthesis include: (1) Peptide Synthesis Interscience, New York, 1966; (ii) The Proteins, Vol. 2, Academic Press, New York, 1976 (iii) Peptide Synthesis (in Japanese), Maruzen Co., 1 975; (iv) Basal synthesis and synthesis (BasiCs an(j Experiment of Peptide Synthesis) (in Japanese), Maruzen Co ., 37 201211250 1 985; (v) Development of Pharmaceuticals (second volume) (in Japanese), Vol. 14 (peptide synthesis), Hirokawa, 1991; (vi) W099/67288; and (vn) Barany G. & Merrifield RB, Peptides Vol. 2, Solid Phase Peptide Synthesis", Academic Press, New York, 1980, 100-118 〇 or 'The invention can be obtained by adapting to any genetic engineering method known to produce peptides The peptide (for example, M〇rris〇n plant j Bacteri〇i〇gy 1977, 132: 349-51; C1ark-Curtiss & Curtiss, Methods in Enzymology (eds· Wu et al ) 1983, 1〇1: 347_62 ) 〇 For example, 'First prepare a suitable one The vector 'has a polynucleotide that encodes the target peptide in an expressible form (eg, downstream of the regulatory sequence corresponding to the promoter sequence) and transfects the vector into a suitable host cell. Such a vector is provided to the host cell. The host is then cultured to produce a (four) interesting peptide. A 7/7 translation system can be used to generate a peptide such as 。. IV. Polynucleotides The present invention provides polynucleotides, peptides, etc. These include From nature

Accession No. ΑΒ057596, or NM_1 38959 (eg, a sequence encoding a polynucleotide of any of the above-described benefits of the present invention (GenBank NM-001172411, 001172412 ID: 68)) and 38 201211250 Those with their conservatively modified nucleotide sequences. The phrase "conservatively modified nucleotide sequence" refers to a sequence which encodes the same or substantially the same amino acid sequence. Due to the degeneration of the gene code, a large number of functionally identical nucleic acids encode any known protein. For example, the codes GCA, gcc' and GCU all encode amino acid alanine. Therefore, by specifying a position of alanine by a password, the password can be changed to any of the above-mentioned correspondences that do not change the encoded peptide. Cryptography. This nucleic acid change is a "silent variation" which is a conservative modification. Each nucleic acid sequence encoding a peptide also describes every possible silent change in the nucleic acid. The skilled artisan will appreciate that each code in the _nucleic acid (except AUG, which is originally the only cryptic acid thiol acid, and butyl (3) which is originally a tryptophan-only code) can be modified to produce a functionally identical molecule. Each of the silent changes in the nucleic acid encoding a peptide is suggested to be disclosed in each of the disclosed sequences. The multinuclear (four) of the present invention may be composed of DNA, RNA and its derivatives. As is well known in the art, DNA molecules are suitably composed of bases, such as naturally occurring assays A, T, C and G, *T being (iv) substituted in the brain. Those skilled in the art will appreciate that non-naturally occurring bases are also Included in the polynucleic acid. The polynucleic acid of the present invention encodes a plurality of tokens of the invention, with or without an intermediate amino acid sequence. For example, an intermediate amino acid sequence can provide a multinuclear acid. A bitter acid or a translated peptide-cleavage site (eg, an enzyme recognition sequence). Further sequences up to encode the invention, the polynucleotide may include any additional coding sequence. For example, a polynucleotide 39 201211250 may be a recombinant polynucleotide comprising a regulatory sequence required for the performance of a peptide, or may be a vector (plastid) having a marker gene and such a gene. Generally, β may be prepared by using the recombinant polynucleotide. Operation via polynucleotides using general recombinant techniques such as polymerase and endonuclease. Both recombinant and chemical synthesis techniques can be used to generate the polynucleotides of the invention. For example, by inserting into a suitable A vector can produce a polynucleotide that can be expressed when transfected into a competent cell. Alternatively, a polynucleotide can be amplified using pCR technology or in a suitable host (see, for example, Sambrook ez" /., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1989) Alternatively, using solid state, techniques such as Beaucage SL & Iyer RP, Tetrahedron 1992, 48: 2223-311; Matthes et aL, EMBO J 1 984 Polynucleotides can be synthesized as described in 3: 801-5. V. Exosomes The present invention further provides intercellular vesicles called exocytosis, which exhibit a complex formed between the peptide of the present invention and the surface of human leukocyte antigen. . For example, exocytosis can be prepared by using the method detailed in Japanese Patent Application Kohyo Publications Nos. Hei 11-510507 and w〇99/03499 and using antigen-expressing cells obtained from a patient treated and/or avoided. body. The exosome of the present invention can be vaccinated as a vaccine, similar to the peptide of the present invention. The human leukocyte antigen form included in the complex must be compatible with the human leukocyte antigen form of the individual in need of treatment and treatment. For example, for Japanese, HLA-A2 (especially HLA-A .0201 and HLA-A*〇206) is often suitable. The use of the A2 type, which is highly expressed among Japanese and Caucasians, helps to obtain effective results' and subtypes such as A* 020 1 and A 0206 provide use. The human leukocyte antigen form of the patient to be treated is generally pre-study on a technical bed, which can appropriately select a peptide having a high binding affinity for the antigen or exhibiting cytotoxic T lymphocyte-induced properties via the antigen. The peptide. Furthermore, in order to obtain a peptide exhibiting both high binding affinity and cytotoxic T lymphocyte evokance, one or two or several amino acids can be performed based on the amino acid sequence of the naturally occurring VANGL1 partial peptide. Replace, delete or add. In the case where the A2 type HLA antigen is used for the exosome of the present invention, the peptide comprising the sequence identification number: [, 12 and 21 has a particular effect. In some embodiments, the exosome of the present invention exhibits a complex of the peptide of the present invention and the HLA-A2 antigen on the surface of the exosome. VI. Antigen presenting cells (APCs) The present invention also provides isolated antigen presenting cells which exhibit a complex formed between a HLA antigen and a peptide of the present invention on its surface. The antigen presenting cells may be derived from a patient being treated and/or avoided, and may be administered as a vaccine by itself or in combination with other drugs including the peptide of the present invention, exosome or cytotoxic lymphocytes. . The antigen-presenting cells are not limited to a specific kind of cells, and include dendrites, cell cells, Langerhans cells (Langerhans cei 1 ), macrophages, β cells 41 201211250 and activated tau cells 'known to express proteins ( The proteinaceous antigen is recognized by the lymphocytes on its cell surface. Since dendritic cells are a typical antigen-presenting cell, they have the strongest cytotoxic τ lymphocyte-inducing effect in antigen-presenting cells, and dendritic cells are supplied using antigen-presenting cells such as the present invention. For example, an antigen-presenting cell can be obtained by inducing dendritic cells derived from peripheral blood mononuclear cells with 7/7 Η h叩 or 叩 with the peptide of the present invention (stimulation). When the peptide of the present invention is administered to an individual, an antigen presenting cells expressing the peptide of the present invention is induced in the body of the individual. Therefore, the antigen-presenting cells of the present invention can be obtained by collecting antigen-presenting cells from the individual after administration of the peptide of the present invention to a single body. Alternatively, the antigen-presenting cells of the present invention can be obtained by contacting antigen-presenting cells collected from an individual with the peptide of the present invention. The antigen presenting cells of the present invention can be administered to one body by itself or in combination with other drugs including the peptide of the present invention, exosome or cytotoxic lymphocytes to induce an anti-cancer immune response in the individual. For example, the administration of e may include the steps of: a: collecting antigen presenting cells from a first individual, b. contacting the antigen presenting cells of step a with a win, and c: administering the antigen presenting cells of step b to one The second individual. The first individual and the second individual may be the same individual or may be different individuals. The antigen-presenting cells obtained from step b can be administered as a vaccine for treating and/or preventing cancer, and examples of cancer include, but are not limited to, bladder cancer, breast cancer, cervical cancer, cholangiocarcinoma, endometrial Disease, liver cancer, non-42 201211250 " field cell lung cancer 't sarcoma, pancreatic cancer, small cell lung cancer and acute myeloid leukemia. The present invention also provides for the manufacture of a pharmaceutical composition comprising antigen presenting cells, or a gas path, wherein the method comprises the step of mixing or formulating the peptide of the present invention with a pharmaceutically acceptable carrier. According to one aspect of the present invention, the antigen presenting cells of the present invention have a high degree of cytotoxicity of n τ lymphocyte inducing ability. In the case of "high degree of cytotoxic T lymphocyte evokability", the degree of contact with the peptide by the antigen-presenting cells or with the peptide which is incapable of inducing the cytotoxic T lymphocytes is highly correlated. The antigen having a high degree of cytotoxic T lymphocyte evoked ability can be prepared by a method comprising the step of transferring a polynucleotide encoding the peptide of the present invention to an antigen-presenting cell, comprising the method of y/7 Fi. Present the cells. The introduced gene can be in the form of DNA or RNA. Examples of the introduction method include 'there is no particular limitation, and various methods generally performed in the field' can use, for example, lipofection, electroporation, and calcium phosphate methods. More specifically, it can be performed as in Cancer Res 1 996, 56: 5672-7; J Immunol 1 998, 161: 5607-13; J Exp Med 1 996, 1 84: 465-72;

Japanese Translation of International Publication No 2000-50 9281. By transferring a gene into an antigen-presenting cell, the gene undergoes transcription, translation, and the like in the cell, and the protein obtained thereafter is treated by MHC Class I or Class II, and is subjected to a presentation route to present a partial peptide. In some embodiments, the antigen of the present invention presents cells, and the antigen exhibits 43 201211250 cells exhibiting a complex of the peptide of the present invention and the HLA-A2 antigen on the surface thereof. VII. Cytotoxic T lymphocytes (CTLs) are resistant to any of the peptide-induced cytotoxic T lymphocyte enhancements of the present invention. Fi is an immunological response to cancer cells, and thus can be used as a disease, similar to a peptide. The present invention therefore provides an isolated cytotoxic tau lymphocyte which is specifically induced or activated by any of the peptides of the present invention. Such a cytotoxic tau lymphocyte can be obtained by (1) the peptide of the present invention Administering to a single body; or (2) contacting antigen-presenting cells from an individual with CD8-positive cells or peripheral blood mononuclear lymphocytes with a peptide of the invention such as η (stimulation); or (3) CD8-positive cells or Peripheral blood mononuclear lymphocytes//7 are combined with antigen-presenting cells or exosomes on the surface of the complex expressing HU antigen and peptide; or (4) including

Cellular receptor (TCR), in the paragraph.

VANGL1', for example, cancer cells, or because of the stimulation of peptides by the peptides, can be used as a target for activated cell toxic lymphoblastic challenge. In some embodiments, the cytotoxic sputum lymphocytes of the present invention are cytotoxic sputum lymphocytes which recognize cells which express a complex of the HLA-A2 antigen and the peptide of the present invention. In the context of a cytotoxic sputum lymphocyte, the phrase "recognizing a cell" means binding to a complex of the HLA_A2 antigen on the cell surface and a peptide of the present invention via its TCR and exhibiting specific cell cytotoxicity against the cell. T lymphocyte activity. Herein, "specific cytotoxic tau lymphocyte activity means a cell which exhibits an anti-HLA-A2 antigen and a complex of the peptide of the present invention" but not to other cells. VIII. T cell receptor (TCR) The present invention also provides a The composition comprises a nucleic acid encoding a multi-peptide which can form a subunit of a T cell receptor, and a method of using the same. The subunit of the T cell receptor has the ability to form a T cell receptor' which confers specificity to antitumor The T cells of the cells, the tumor cells exhibit VANGL 1. The α-and/5-branched nucleic acids of the tau cell receptor subunits of the cytotoxic T lymphocytes can be confirmed by using methods known in the art, and the cells are Toxic tau lymphocytes are induced by one or more peptides of the invention (W02007/032255 and Morgan et al., J Immunol, 171, 3288 (2003)). For example, preference is given to analysis by polymerase chain reaction method. T cell receptor subunit. The polymerase chain reaction primer used for analysis can be, for example, a 5,-R primer (5-gtctaccaggcattcgcttcat-3') is a 5' end primer (SEQ ID NO: 70) and 3-TRa -C introduction 45 201211250 (5,-tc Agctggaccacagccgcagcgt-3,) specific to the T cell receptor alpha chain C region (SEQ ID NO: Π), 3-TRb-Cl primer (5'-tcagaaatcctttctcttgac-3') specific to the T cell receptor beta chain C1 region (sequence Identification number: 72) or 3-TRbeta-C2 primer (5,-ctagcctctggaatcctttctctt-3*) is specific to the T-small-receptor beta chain C2 region (SEQ ID NO: 73) as a 3'-end primer, but not limited to The extracted T cell receptor can bind to the target cell expressing VANGL1 peptide with high affinity' and can effectively kill the target cell expressing VANG L1 by the need of /7f/ κσ and //7 ηΎγο. The nucleic acid sequences of the subunits can be combined into a suitable vector, such as a retroviral vector. Such vectors are well known in the art. Nucleic acids or vectors comprising the same can be transferred to a tau cell, for example, from a patient. T cells. Usefully, the present invention provides a f-the-shelf composition that allows rapid modification of tau cells (or other mammalian ones) possessed by a patient to quickly and easily produce excellent cancer cell kills. special The modified sputum cell can specifically recognize the complex of the peptide of the present invention and the HLA molecule, and when the sputum cell receptor is on the surface of the sputum cell, the specific activity of the τ cell against the target cell is given. Specific recognition of the above complexes can be confirmed by any known method, and preferred methods include, for example, tetramer analysis using Hu molecules and the peptide of the present invention, and ELI SPOT analysis. By performing an EL I SPOT analysis, it is confirmed that T cells expressing a tau cell receptor on the cell surface recognize a cell by the T cell receptor and the message is transmitted into the cell. It can also be performed by known methods when the complex is present on the surface of T cells. 46 201211250 The above complex can be administered to confirm the cytotoxic activity of a cell. Preferred methods include, for example, cytotoxic activity assays for anti-HLA positive target cells, such as chromium release assays. The present invention also provides cytotoxic T lymphocytes which are transcribed by a nucleic acid encoding a T cell receptor subunit polypeptide which binds to a VANGL1 peptide such as SEQ ID NO: 1 and 21 in the presence of HLA-2. Guided to prepare. The transduced cytotoxic T lymphocytes can be /7 1 / (9 self-directed to cancer cells ' and can be expanded by well-known culture methods (eg Kawakami to Zha, J Immunol., 142, 3452-3461 ( 1 989)) The cytotoxic T lymphocytes of the present invention can also be used to form a consensus immunological composition that is effective in treating or avoiding cancer in a patient in need of treatment or protection (W02006/031221). IX. Compared with normal tissues, VANGL1 is particularly enhanced in cancer, such as bladder cancer, breast cancer, cervical cancer, cholangiocarcinoma, neurite endometriosis, liver cancer, non-small cell lung cancer, osteosarcoma, and pancreas. Cancer, small cell lung cancer and acute myeloid leukemia, the peptide or polynucleotide of the present invention can be used for the treatment and/or prevention of cancer, and/or to avoid recurrence after surgery. Accordingly, the present invention provides a pharmaceutical composition or The agent is used for the treatment and/or prevention of cancer, and/or the avoidance of recurrence after surgery for such cancer, such composition or reagent comprises as active ingredient one or more of the active peptide or polynucleic acid of the present invention. . The peptide of the present invention can be expressed on any of the aforementioned exosome or cell surface, such as antigen-presenting cells, for use as a pharmaceutical composition or reagent for 47 201211250. In addition, the above-mentioned cells which are subject to any win of the present invention Toxic T lymphocytes can also be used as the active ingredient of the pharmaceutical grades of the invention: or agents. The pharmaceuticals and compositions or agents of the invention also provide for use as a vaccine.

In the context of the present invention, the phrase "vaccine" fa 咅 * L L L L L L L L L L L L L L L L 意 意 意 意 意 意 意 意 意 意 意 意 意 意 意 意 意 意 意 意 意 意 意The function of force. The pharmaceutical composition j(7) of the present invention is cold-sucking and/or avoids cancer from, and/or avoids recurrence after surgery. In an individual body or patient, the individual or patient includes a human and any other mammal, i物物 includes, but is not limited to, mice, rats, guinea pigs, rabbits, cats, dogs, @I ^ J磾 half, goats, pigs, cows, horses, monkeys, baboons and chimpanzees, especially a commercially important animal. Or domesticated animals. In another embodiment, the present invention is further characterized by the use of an active ingredient for a therapeutic ingredient selected from the group consisting of: (a) a peptide of the invention; encoded as disclosed herein (b) a nucleic acid of a formable peptide; (c) an exosome expressing the exosome of the invention; and an antigen presenting cell of the peptide on its face or (d) or an active ingredient' - for the treatment of (d) 'active ingredient selected from: disease or tumor 48 201211250 (a) the peptide of the invention; (b) in a form that can be expressed, such a nucleic acid encoding such a peptide as disclosed herein; c) an antigen presenting cell or exocytosis which exhibits a peptide on the surface of the peptide of the present invention; and (d) a cytotoxic tau lymphocyte of the present invention. Alternatively, the invention further provides a method or process for the manufacture of a pharmaceutical composition or agent for treating or preventing cancer or a tumor, wherein the method or process comprises formulating a pharmaceutically or physiologically acceptable carrier with an active ingredient. In the step, the active ingredient is selected from: (a) a peptide of the present invention; (b) a form of expression, a paper, a nucleic acid encoding the peptide as disclosed herein; (C) representing the present invention - the antigen on the surface of the skin glycosides is present as a cell or exosome; and (d) the cells of the invention are toxic to the lymphocytes. In another embodiment, the method also provides a method or process for making a pharmaceutical composition for treating or avoiding cancer or a tumor, and the method or process of the method comprises administering a pharmaceutically acceptable $, ν physiology The step of mixing the acceptable carrier with an active ingredient/knife, wherein the dry active ingredient is selected from: (a) the peptide of the present invention; (b) the nucleic acid of the μ peptide in a formable form (c) encodes such a victory as disclosed herein (c) that the present invention is superior to antigen-presenting cells on its surface or 49 201211250 exosome; and (d) the cytotoxic tau lymphocytes of the present invention. The pharmaceutical compositions or agents of the invention provide for the use of, for example, a vaccine. In the present invention, the phrase "vaccine" (also referred to as a consensus immunological composition) means a composition or reagent which has the function of inducing anti-tumor immunity by inoculation into an animal. According to the present invention, it has been found to have sequence recognition. No.: The peptide of the amino acid sequence in 1, 12 and 21 is an HLA-A2-restricted epitope peptide or candidate which induces a strong and specific immune response. Therefore, it includes any sequence identification number 1 The pharmaceutical composition or agent of the present invention having a peptide of the amino acid sequence of 12 and 21 is particularly suitable for administration to an individual having an HLA antigen of HLA-A2. The same is provided to a polynucleotide comprising any of these peptides ( That is, a pharmaceutical composition or agent of the polynucleotide of the present invention. The cancer treated by the pharmaceutical composition or agent of the present invention is not limited to and includes any cancer in which VANGL1 (eg, 'overexpressed'), including but not limited to Bladder cancer, breast cancer, cervical cancer, cholangiocarcinoma, neurite endometriosis, liver cancer, non-small cell lung cancer, osteosarcoma, pancreatic cancer, small cell lung cancer and acute myeloid white blood The pharmaceutical composition or agent of the present invention may include, in addition to the above-mentioned active ingredients, other traits having the ability to induce cytotoxic T lymphocytes against cancer-like cells, other polynucleotides encoding the other peptides, and others. Other peptide cells or the like. Here, other peptides having the ability to induce cytotoxic T lymphocytes against cancer-like cells are exemplified by cancer-specific antigens (for example, confirmed tumor-associated antigens), but are not limited thereto. 50 201211250 4 The pharmaceutical composition or reagent of the present invention may be 114 t. The therapeutic substance is m, and the anti-tumor effect is included as needed. The activity may be as long as the substance does not inhibit the active ingredient. The peptide of the present invention. For example, the recipe spoon includes 1 and 'and. Things, analgesics, and chemotherapy are similar. In addition to - or a plurality of other pharmaceutically ... ', the amount of the pharmaceutical substance or composition of the present invention may be based on: 5: followed by or simultaneously, with the pharmaceutical list, such as which pharmaceutical substance or combination of diseases to use The plan and method of administration.

It should be understood that, in addition to the ingredients specifically mentioned herein, the pharmaceutical composition of the present invention or the test composition of the present invention includes other compositions generally in the technical field, and eight have The form of the formula in question. In one embodiment of the invention, the pharmaceutical compositions or agents of the invention may be included in the manufacture of the article and kit' which comprise materials useful for the pathological condition of the condition to be treated, such as cancer. The article of manufacture may comprise a container of any of the pharmaceutical compositions or agents of the invention. Suitable gluten includes bottles, vials (v i & 1, disc-*-4? bottle Ula丨) and manifolds. The container can be formed from a variety of materials such as glass or plastic. The label on the container indicates that the composition or agent is used to treat or avoid one or more of the conditions. The label can also indicate the indication of administration. In addition to the above-described containers, the kit comprising the pharmaceutical composition or agent of the present invention may further comprise, if desired, a second container for storing a pharmaceutically acceptable diluent. It may include other materials that are desirable from a commercial or user point of view, including other buffer solutions, diluents, filters, needles, syringes, and package inserts with instructions for use. 51 201211250 A pharmaceutical composition or agent can be presented in a pack or dispenser if desired, which can comprise one or more unit dosage forms containing the active ingredient. The package may for example comprise a metal or plastic foil, such as a bl ister pack. The pack or dispenser can be accompanied by a medication indication. (1) Pharmaceutical composition comprising a peptide as an active ingredient The peptide of the present invention can be directly administered as a pharmaceutical composition or reagent, and if necessary, it has been formulated by a general formulation method. In the following examples, there are no particular limitations other than the peptide of the present invention, if appropriate, including carriers, excipients, and the original use as a drug. Examples of the above carrier are sterile water, physiological saline, phosphate buffer solution and culture liquid (cul1; ure f luid) and the like. Further, if necessary, the pharmaceutical composition or substance may contain a scorpion, a suspension, a preservative, a surfactant, and the like. The pharmaceutical compositions or agents of the invention are useful for anti-cancer purposes. The peptide of the present invention can be prepared by combining two or more peptides of the present invention to induce cytotoxic tau lymphocytes with /F/叩. The combination of peptides can be in the form of cocktails or can be combined with each other using standard techniques. For example, the peptide can be chemically linked or behave as a single fused multipeptide sequence, which can have one or several amino acids as a linker (eg, Lysine linker: Κ·S. Kawamuraei a/. J. Immunol. 2002, 168: 5709-571 5). The peptides to be combined may be the same or different. By administering the peptide of the present invention, the HLA antigen, the high density exhibits the peptide on the antigen presenting cells, and then the cytotoxic T lymphocytes which are formed in response to the complex between the peptide and the HLA antigen. Induced. Alternatively, the antigen presents a fine 52 201211250 cells (e.g., 'dendritic cells') that are removed from the individual and then stimulated with the peptide of the present invention to obtain antigen presenting cells that exhibit any of the peptides of the present invention on their surface. The appropriate antigen-presenting cells are then administered to the individual to induce cytotoxic tau lymphocytes in the individual, i thus increasing the invasion toward the tumor-associated endothelium. A pharmaceutical composition or agent comprising a therapeutic peptide of any of the present invention as an active ingredient for treatment and/or avoidance of cancer may also comprise an adjuvant to effectively establish cellular immunity. b may be administered together with other active ingredients, or they may be administered It is administered as a fine granule. An adjuvant refers to a compound that, when administered (or sequentially) with an immunologically active protein, enhances the anti-protein immune response, and can be used as an adjuvant, including in the literature (clinMicr〇bi〇iRev 1 994' 7: 277-89). Examples of adjuvants include succinate, hydrazine, cholera toxin, salmonella toxin, Freund's incomplete adjuvant (I mplete Freuncr s adj_t, IFA), Complete Freund, s adjuvant, CFA ), ISCOMatrix 'CSF, CpG, 〇/w emulsions and the like, but not limited to them. Further, in the liposome formulation and the fine particle formulation, the peptide is linked to a few micron diameter beads 'and in the formulation' can conveniently use the lipid linked to the peptide. In another embodiment of the invention, the peptide of the invention may also be administered as a pharmaceutically acceptable salt. Preferable examples of the salt include a metal salt, a metal salt, a salt having an organic base, a salt having an organic acid, and a salt having an inorganic acid. As used herein, 'a pharmaceutically acceptable salt, means maintaining the biological effectiveness and properties of the compound and obtaining a chemical or inorganic acid, such as 53 201211250 hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methyl hydrazine. Some salts of methanesulfonic acid, ethanesulfonic acid, P_toluenesulf〇nic acid, salicylic acid, and the like. In some embodiments, 'the invention' A pharmaceutical composition or reagent comprises a component which initiates a cytotoxic T lymphocyte. A defined lipid is a component of a cytotoxic T lymphocyte that can initiate an antiviral antigen. For example, a palmitic acid residue can be attached to an amine. The e-and amino-amino group of the acid residue, and then linked to one of the peptides of the present invention. The lipid peptide can then be directly administered into the micelle or granule, incorporated into the liposome or emulsified in an adjuvant. Another example of a lipid-initiating cytotoxic lymphocyte reaction, and lipoproteins such as tristearic acid-S glycerol cysteinyl-serylserine

(tripalmitoyl S glycerylcysteinyl-seryl-serine, P3C SS) can be used to initiate cytotoxic tau lymphocytes when covalently attached to a suitable peptide (see 'Deres et al., 1 989, 342: 5 61 - 4) The method of administration of sputum may be oral, intradermal, subcutaneous, or intravenous injection, such as: and the vicinity of the systemic administration or local administration to the target location may be a single-agent or may be added by multiple administrations. The peptide agent of the present invention,

It can be adjusted according to the disease to be treated, the age of the patient, the weight, the method of investing, and the like, and it is too happy.

The peptide dose of the sera is generally 0.001 mg J 1, 〇〇〇 mg ′ for example 〇 〇 1 to 100 mg, for example 〇 1 mg to 1 〇 mg and can last for several days to several months — only a long time. Those skilled in the art will be able to select a suitable dosage when appropriate. 54 201211250 (2) Pharmaceutical composition comprising a polynucleotide as an active ingredient The pharmaceutical composition or agent of the present invention may also comprise a nucleic acid encoding the peptide disclosed herein in an expressible form. The phrase "in an expressible form" herein means a polynucleotide which, when introduced into a cell, is expressed as a multi-peptide which induces anti-tumor immunity. The nucleic acid sequence of the polynucleotide of interest in the _ representative embodiment includes regulatory elements necessary for the expression of the polynucleotide. Polynucleotides can be assembled to achieve stable insertion into a genomic cell (see, for example, Thomas KR & Capecchi MR, Cell 1 987' 51: 503-1 2, for the description of homologous recombination cassette vectors. See, for example, Wolff eia/., Science 1990, 247: 1465-8; US Patent Nos. 5,580,859; 5,589,466; 5,804,566; 5,739,1 18; 5,736,524; 5,679,647; and WO 98/04720). Examples of DNA delivery technologies include "naked DNA", delivery (bupi vacaine, polymer, peptide centered) delivery, cationic lipid complexes and particles centered ("gene grab") or pressure-centered delivery (see, For example, US Patent No. 5, 922, 687). The peptide of the present invention can also be expressed by a viral or bacterial vector. Examples of performance vectors include attenuating viral hosts such as vaccinia or fowl pox. This method involves the use of a vaccinia virus, such as a vector to represent the nucleotide sequence encoding the peptide. By introducing a host- & recombinant vaccinia virus, the immunogenic peptide is expressed and thus causes an immune response. The vaccinia carrier and method which are effective in the immunization step are described, for example, in U.S. Patent No. Another carrier includes BCG (Baci 1 le Calmette Guerin). The BCG vector 55 201211250 is described in Stover et al., Nature 1991, 351: 456-60. A variety of other vectors useful for therapeutic administration or immunization, such as glandular and adenovirus-related vectors, retroviral vectors, Salmonella typhi vectors, detoxified anthrax toxin vectors, and the like are apparent. See, for example, Shata ei a/., Mol Med Today 2000, 6: 66-71; Shedlock et aJ., J Leukoc Biol 2000, 68: 793-806; Hipp ei a/., In Vivo 2000, 14: 571- 85. Delivery of a polynucleotide into a patient can be direct, in which case the individual is directly exposed to a vector carrying the polynucleotide, or indirectly, in the example of which the cell is first i·/7 to the polynucleotide of interest. The acid is transformed and the cells are then transferred into the patient. These two methods are known to be 77 η·叩 and ez f/ κσ gene therapy. For a general review of methods of gene therapy, see Goldspiel 5, Clinical Pharmacy 1 993, 1 2: 488-505; Wu and Wu, Biotherapy 1991, 3: 87-95; Tolstoshev, Ann Rev Pharmacol Toxicol 1993, 33: 573- 96; Mulligan, Science 1993, 260: 926-32; Morgan & Anderson, Ann Rev Biochem 1993, 62: 191-217; Trends in Biotechnology 1993, 11 (5): 1 55-21 5 ). A method generally used in the recombinant DNA technique of the present invention is described by Ausubel ei, in Current Protocols in Molecular Biology, John Wiley & Sons, NY, 1993; and Krieger, in Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY, 1 990 stated. The method of administration can be used for oral, intradermal, subcutaneous, intravenous injection or the like in the vicinity of the system and the systemic administration or topical administration to the target site. A single-line drug can be administered or added by multiple administrations. The dosage of the polynucleic acid in a suitable carrier or in a multinucleated (tetra) transformed cell encoding the peptide of the present invention can be suitably adjusted depending on the disease to be treated, the age of the patient, the body weight, the method of administration, and the like. And the dosage of the peptide of the present invention is generally from 0.001 mg to 1 mg, for example, from 1 mg to 1 g, for example, from 1 mg to 1 mg, and may be used once every few days to several times. Dosing once a month. Those skilled in the art will be able to suitably select a suitable dosage. X. Method of using peptide, exosome, antigen-presenting cells and cytotoxic T lymphocytes The peptides and polynucleotides of the present invention can be used to prepare or induce antigen-presenting cells and cytotoxic T lymphocytes. The extracorporeal and antigen-presenting cells of the present invention can also be used to induce cytotoxic T lymphocytes. The phenotype, polynucleotide, exosome and antigen presenting cells can be used in combination with any other compound as long as the additional compound does not inhibit the cytotoxic lytic lymphocyte priming ability. Thus, any of the above-described pharmaceutical compositions or agents of the invention can be used to induce cytotoxic lymphocytes. In addition, those including peptides and polynucleotides can also be used to induce antigen-presenting cells, as explained below. (1) Method for inducing antigen-presenting cells The present invention provides a method for inducing antigen-presenting cells having a high cytotoxic axillary lymphocyte-inducing ability using the peptide or polynucleotide of the present invention. The method of the present invention comprises the step of contacting the antigen presenting cells with the peptide of the present invention by h or h h叩. For example, 57 201211250 A method of contacting an antigen presenting cell with a peptide can include the steps of: a: collecting antigen presenting cells from one body; and b' contacting the antigen presenting cells of step a with the peptide. The antigen presenting cells are not limited to a specific kind of cells, and include dendritic cells, Langerhans ceu cells, macrophages, B cells, and activated tau cells, which are known to express proteins (pr〇teinace〇us). The antigen is recognized by the lymphocytes on its cell surface. Preferably, the dendritic sputum can be used because of the strongest cytotoxic T lymphocyte evoking ability in the antigen-presenting cells. Any of the peptides of the invention may be used by themselves or with other peptides of the invention. On the other hand, when preparing the peptide of the present invention to a single body, the antigen is in contact with the peptide, and the I iT? F/FC? is contacted with the peptide, thereby inducing the ability to induce the cytotoxic T lymphocyte in the body of the individual. The antigen presents the cells. Thus the q invention includes a method of administering a peptide of the invention to an individual. Similarly, when the presently expressible form is administered to the present polynucleic acid to the individual, the present invention overcomes the use of HFO to contact the antigen, thereby inducing a high cytotoxic lymphocyte evoked ability in the individual's sputum. The antigen exhibits a cytokine, and the present invention includes administration of the polynuclear bud acid of the present invention to a body of 3, and the expression of oxime is described in the above paragraph 4 "IX. Pharmaceutical composition" (2) The pharmaceutical composition comprises a multinuclear The present invention may include a step of introducing a polynucleic acid of the present invention into an anti-shoulder cell to prepare a cell having a cytotoxic lymphocyte-inducing ability. For example, The method may comprise the steps of: 3 collecting antigen presenting cells from the individual; and 58 201211250 b: introducing a polynucleotide encoding one of the peptides of the invention. This may be performed as described in the paragraph "VI. Antigen presenting cells" Step b. Or the present invention provides a method for preparing an antigen-presenting cell which specifically induces cytotoxic T lymphocyte activity against VANGL1, wherein the method may comprise one of the following steps: (a) presenting the antigen The cell is contacted with a peptide of the present invention at e, f/fo or //7f/ko; and (b) a polynucleotide encoding one of the peptides of the present invention is introduced into the antigen presenting cell. Or the invention provides induction A method of presenting a cell having an cytotoxic T lymphocyte-inducing ability, wherein the method comprises the steps of:

Ca) contacting the antigen presenting cells with the peptide of the present invention; and (b) introducing the polynucleotide encoding one of the peptides of the present invention into the antigen presenting cells. The method of the present invention can be carried out at "W μ or ^ (7). The method of the present invention can be carried out at 2 Λ η or ^ h叩. The antigen for the induction of antigen-presenting cells with cytotoxic lymphocyte-inducing ability The presenting cells may preferably be antigen presenting cells expressing the HLA-A2 antigen. Such antigen presenting cells may be peripheral blood mononuclear cells obtained from individuals whose HLA antigen is HLA-A2 by a method well known in the art. The antigen-presenting cell induced by the present invention may be a compound exhibiting the complex of the peptide of the present invention and the HLA antigen (HLA-A2 antigen) on the surface of the 59 201211250 antigen. When the antigen is induced by the method of the present invention When the cells are presented to a body to induce an anti-cancer immune response in the individual, the individual is preferably a sputum; the original appears to be the same cell obtained. However, the individual may be different from the antigen presenting cell provider. One, as long as the individual is presented with the same HLA type as the antigen presenting cell provider. In another embodiment, the invention provides for inducing cytotoxic lymphocyte induction An antigen or antigen presenting a cell, and such reagent or composition includes one or more peptides or polynucleotides of the invention. In another embodiment, the invention provides a peptide of the invention or encodes this The polynucleotide of the peptide is used in the manufacture of a reagent or composition formulated to induce antigen-presenting cells. Or the invention further provides the peptide of the invention or the polynucleotide encoding the peptide for cytotoxicity in induction The use of antigens for the induction of TNF-inducing ability in cells. (2) Method for inducing cytotoxic thymocytes. The present invention also provides cells for inducing cells using the peptide, polynucleotide or exosome or antigen-presenting cells of the present invention. Method for killing a tau lymphocyte. The present invention also provides a method for inducing a cytotoxic axillary lymphocyte using a polynucleotide encoding a multi-peptide, the ability of the multi-peptide to form a tau cell receptor-human unit And the tau cell receptor subunit recognizes a complex of the invention and the HLA antigen. Preferably, the method for inducing the cytotoxic tau lymphocyte comprises at least one step of free selection. Among them: a: a CD8-positive tau cell is contacted with an antigen-presenting cell and/or an external 60 201211250 sporozoite, and the antigen-presenting cell and/or the exosome exhibits an HLA antigen and the peptide of the present invention. The complex is on its surface, and b: a polynucleotide is introduced into a CD8 positive cell, wherein the polynucleotide encodes a multi-peptide that has the ability to form a T cell receptor subunit' The T cell receptor subunit recognizes a complex of the inventive peptide and the HLA antigen. When the peptide, polynucleotide, antigen presenting cell or exosome of the present invention is administered to a body, the individual is The intensity of the immune response that induces cytotoxic T lymphocytes in vivo and targets cancer cells is enhanced. Therefore, the method of the present invention comprises administering the peptide, polynucleotide, antigen presenting cell or exocytosis of the present invention. The steps to one body. Alternatively, cytotoxic tau lymphocytes can also be induced by <? especially using them, and the activated cell-killing axillary lymphocytes can be returned to the individual after induction of the cytotoxic T lymphocytes. For example, the method can include the steps of: a: collecting antigen presenting cells from one body; b' contacting the antigen presenting cells of step a with the peptide; and co-culturing the antigen presenting cells of step b with CD8 positive cells. An antigen-presenting cell to be co-cultured with CD8-positive cells in the above step c can also be obtained by transferring a gene comprising the polynucleotide of the present invention into an anti-presenting cell, as in the aforementioned paragraph "VI. Antigen-presenting cells, The preparation is, however, the present invention is not limited thereto, and thus includes any antigen-presenting cells which effectively express a complex of the HLA antigen and the peptide of the present invention on the surface. Instead of expressing the antigen, the cell may also be used. De-antigen and 61 201211250 The complex of the peptide of the present invention is exosome on its surface. The present invention may comprise a complex which exhibits a hla 17 and a peptide of the present invention. The external exosome of the surface and the step of the invention are successful, ^ _, and cold-raised. The outer body can be prepared by the method described in the paragraph "v from the vomiting". In addition, introduction of (10) positive cells by a gene comprising a multi-nucleotide acid encoding a tau cell streptozotocin combined with a win of the present invention may also be used.

Inducing cytotoxicity of P1 lymphocytes. This transduction can be performed as described in the aforementioned paragraph "VIII·τ έField Receptor (TCR)". The method of the present invention can be performed by ^· · π』IJ Vitro' ex νιν〇 氙 in νϊν〇. Preferably, the method of the invention can be performed in one or the other. CD8-positive tau cells for induction of cytotoxic lymphocytes can be prepared from peripheral blood mononuclear cells obtained from one body by methods well known in the art. In a preferred embodiment, the provider of CD8 positive tau cells can be an individual whose HLA antigen is HLA-A2. The cytotoxic tau lymphocytes induced by the present invention are identifiable as cells expressing the complex of the peptide of the present invention and the hla antigen on the surface thereof. When the cell killing T lymphocytes induced by the method of the present invention are administered to a body to induce an anti-cancer immune response in the individual, the individual is preferably the same one obtained for the CD8-positive T cells. However, an individual may be different from a CD8 positive T cell provider as long as the individual has the same HLA type as the CD8 positive T cell provider. Further, the present invention also provides a method or process for the manufacture of a pharmaceutical composition or agent for inducing cytotoxic T lymphocytes, wherein the method comprises the step of mixing or formulating the peptide of the present invention together with a pharmaceutically acceptable carrier.

In another embodiment, the invention provides an agent or composition for inducing a cytotoxic T62201211250 lymphocyte, wherein the agent or composition comprises one or more peptides of the invention, one or more polynucleosides of the invention The acid, one or more antigens present to the cells or exosome. In another embodiment, the invention provides the use of a peptide, polynucleotide, prion-producing cell or exosome of the invention for the manufacture of an agent or composition formulated to induce a cytotoxic tau lymphocyte. Or the present invention further provides for the use of the peptide, polynucleotide, antigen presenting cell or exosome of the present invention for inducing a cytotoxic lytic lymphocyte. (3) Method of inducing immune response Further, the present invention provides a method of inducing an immune response against a disease associated with VANGL1. Suitable diseases include cancer, examples of which include, but are not limited to, bladder cancer, breast cancer 'cervical cancer' cholangiocarcinoma, endometriosis, liver cancer, non-small cell lung cancer, osteosarcoma, pancreatic cancer, small cell lung cancer With acute myeloid leukemia. The method of the invention comprises the step of administering a composition or reagent comprising any of the peptides of the invention or the polynucleotides encoding them. The methods of the invention are also contemplated for administration to any of the peptides of the present invention, exosome or antigen presenting cells. The details refer to the composition of the invention, in particular the composition of the invention; the reagent is part of the use of the vaccine. In addition, the exosome and antigen-presenting cells of the present invention which can be used in the method for stimulating an immunological reaction of the present invention are: finely intercalated in front of "V. exosome" and "Π. (4). Items related to "X. Use of peptides, exosomes, antigen-presenting cells and cytotoxicity 63 201211250 methods for killing tau lymphocytes" (1) and (7). The present invention also provides a method for making 诰^^(4) square m < A pharmaceutical composition of an immunological reaction, or a procedure, wherein the carrier, n is a step of mixing or formulating a winning form of the present invention with a drug. Alternatively, the method of the present invention may comprise administering a method of the present invention. A vaccine or pharmaceutical composition or a reagent, the vaccine or pharmaceutical composition of the present invention comprising: "(a) a peptide of the invention; (b) in a formula 3»·jjy >, encoded as disclosed herein The nucleic acid of such a peptide; (see) the antigen-presenting cell or exosome of the present invention - the peptide on its surface; or (d) the cytotoxic tau lymphocytes of the present invention. In the present invention 4, cancers which overexpress VANGL1 can be treated with these active ingredients. Examples of such cancers include, but are not limited to, bladder cancer, breast cancer, cervical cancer, cholangiocarcinoma, endometriosis, liver cancer, #J ''田月 L lung sarcoma, spleen cancer, small cell lung cancer and Acute myeloid leukemia. Therefore, 'in the case of a vaccine or a pharmaceutical composition or a β-agent comprising an active ingredient, it is preferred to confirm that the degree of expression of VANGL1 is in the cell or tissue to be treated, in comparison with the normal tissue of the same organ. Raise. Accordingly, in one embodiment, the invention provides a method of treating (excessively) expressing a cancer of VANGL1, the method comprising the steps of: I) measuring the degree of VANGL1 expression obtained in a cell or tissue having an individual to be treated by the cancer; II) Comparison of the degree of VANGL1 performance with the normal control group; and 64 201211250 /11) The selection of the above (from at least the injury to the group consisting of (d) to the positive suspension control group compared to the over-expressed MNGU The present invention may also provide a vaccine or pharmaceutical composition or agent comprising at least one component selected from the group of (a) to (4) above for administration to an individual having an overexpressed VANGL1 cancer. In other words, the invention further provides a method of identifying an individual to be treated with the VANGU sin peptide of the invention. [The method includes the step of determining the extent of VANGU I in the cells or tissues of the individual, wherein The degree of normal control is greater than 'this degree indicates that the individual has a cancer that can be treated with the VANG" multi-peptide of the present invention. The method of treating cancer of the present invention is described in more detail below. Any cell or tissue derived from an individual can be used for the determination of VANGU expression as long as it includes the target transcription or translation product of VANGL 1. Examples of suitable samples include, but are not limited to, body tissues or fluids such as blood, saliva and urine. Preferably, the biological sample comprises a cell population comprising an epithelial cell, more preferably the cell or tissue derived from the individual comprises a cell population 'which includes an epithelial cell, more preferably a cancer epithelial cell or a suspected The epithelial cells of the cancerous tissue. Further, if necessary, the cells can be purified from the obtained body tissue or liquid, and then used as a sample derived from the individual. The individual to be treated by the present invention is preferably a mammal. Exemplary mammals include, but are not limited to, for example, humans, non-human primates, mice, rats, dogs, cats, horses, and cattle. According to the present invention, cells or tissues obtained from a body can be assayed. 65 201211250 vANGL1 performance degree. The degree of performance can be determined by the degree of product acidity using methods known in the art. For example, by The human σ (for example, Northern Hybrid) can quantify the mRNA of VANGL1 by using a probe. The detection can be performed on a single piece or array. The use of the array can be preferably used:::VANGLU present level. L1 sequence information, familiar to those skilled in the art can prepare such a probe, for example, the _ 1 probe of the job. If you need a suitable marker to mark the probe, such as reagents: camping substances and isotopes, and The degree of expression of the gene can be measured as the intensity of the heterozygous marker. In addition, the transcription product of vangli can be quantified by using an amplificati〇n_based detectl〇n method (for example, RT_pCR). Such primers can be prepared based on the available sequence information of the gene. In particular, the probe or primer used in the method is hybridized to the field legs of VANGL1 under stringent, moderately severe, low severity conditions. As used herein, the phrase "severe (heterozygous) conditions means that the probe or primer will hybridize to its target sequence, but not to other sequences under this condition. Severe conditions are sequence dependent (seQuence_dependent) and in different environments The difference will be different. A specific sequence of longer sequences is observed at higher temperatures than the shorter sequence. In general, the temperature of a stringent condition selected at a defined ionic strength and pH is below a specific The melting point (Tm) of the sequence is about 5 C ° Tm is the temperature (under a defined ionic strength and pH and nucleic acid concentration) 'under which the probe complementary to the target sequence is 5 〇 under equilibrium to the target sequence. Since there is usually an excess of the target sequence, at Tm, 66 201211250 5G% of the probe is occupied under equilibrium. In general, the severe condition is that the salt concentration is lower than 1·〇M sodium ion, generally about 〇. 1 to 1 〇M sodium ion (or other salt) at ρΗ 7. 〇 to 8.3, and for short probes or primers (eg, 10 to 50 nucleotides), the temperature is at least about 3 (rc, For longer probes or primers, the temperature is Less than 6 〇〇c. Desabilizing substances such as formamide can also be added to achieve severe conditions. The probe or primer of the present invention is generally a substantially purified oligo. Nucleotide. An oligonucleotide generally comprises a region of a nucleotide sequence that is heterozygous under stringent conditions to at least about 2000, 1 〇〇〇, 500, 400, 350, 300, 250, 200, 150, 100, 50 or 25 comprises a consecuti ve sense strand nucleotide sequence of one of the VANGL1 sequences, or a nucleotide sequence comprising an anti-sense strand of one of the VANGL1 sequences, Or naturally occurring mutants of these sequences. In particular, 'for example, in a preferred embodiment, an oligonucleotide having a length of 5-5 长度 can be used as an primer for enlarging the gene to be detected. Preferably, the mRNA or cDNA of the VANGL1 gene can be detected by an oligonucleotide probe or primer having a length of l5_3〇b. The size ranges from at least 10 nucleotides, at least 12 nucleotides, at least 15 Nucleotides, at least 20 nucleotides, at least 25 Nucleotide, at least 30 nucleotides, and probe and primer extensions start at 5 - 10 nucleotides, 1 〇 15 nucleotides, 15 - 20 nucleotides, 2 0 - 2 5 nucleotides and 2 5 - 30 nucleotides. In a preferred embodiment, the length of the oligonucleotide probe or primer can be selected from 15 - 2 5 . Analysis of Nucleotide Probes or Primers for Gene Mapping 67 201211250 Private sequences, devices or reagents are well known in the art (e.g., oligonucleotide arrays or PCR). In these assays, the probe or primer may also include a tag or linker sequence. In addition, the probe or primer can be modified by an affinity ligand that is detectable or to be captured. Or in a heterozygous debt test, a base having a few hundred bases (eg, about 100-200) at least several thousand (for example, about 1〇〇〇-2〇〇〇) in length. Polynucleotides can be used in a probe (eg, Northern blot analysis or cDNA microarray analysis). Alternatively, the translation product can be detected for the diagnosis of the present invention. For example, the amount of VANGL1 protein (SEQ ID NO: 69) or its immunologically active fragment can be detected. A method of measuring the amount of a protein as a transcription product includes an immunoassay method which specifically recognizes the protein using an antibody. The antibody may be single or multiple plants. In addition, any fragment or modification of the antibody (eg, chimeric antibody, scFv, Fab, F(ab') 2, Fv, etc.) can be used to detect 'as long as the fragment or modified antibody is maintained against VANgli The ability to bind proteins. The invention also provides such antibodies against the peptides of the invention and fragments thereof. These methods of preparing these kinds of antibodies for protein detection are well known in the art and any method can be used in the present invention to prepare such antibodies and their equivalents. Another method for detecting the degree of expression of the VANGL1 gene based on the VANGL1 gene translation product 'The staining intensity can be measured by immunohistochemical analysis using an antibody against the VANGL1 protein. That is, in this measurement, strong staining indicates the presence/degree of the increased protein, and at the same time the high degree of expression of the VANGL1 gene.

6S 201211250 It can be confirmed that the degree of expression of a target gene, such as the vangu gene, is increased in cancer cells, and the degree of control from the target gene (for example, the degree in normal cells) is increased, for example, 1%, 25%, , or 5〇%, or an increase greater than 1.1 times, greater than U times, greater than 2. The magnification is greater than: 〇 times 'greater than 10.0 times or more. The extent to which a sample control group collected and stored for a known individual from the individual/the disease stage (cancerous or non-cancerous) is simultaneously measured with the cancer cell. Further, normal cells obtained from a non-cancer region having an organ to be treated for cancer are used as a normal control group. Alternatively, the degree of the control group can be determined by statistical methods based on the results obtained from the analysis of the degree of expression of the VANGL1 gene in a sample of an individual whose disease degree is previously determined. In addition, the control group level can be a database of performance profiles from previously tested cells. Moreover, the degree of expression of the VANGL1 gene in a biological sample according to one aspect of the present invention can be compared with the degree of control groups whose degree of control is determined from a plurality of reference samples. Preferably, a self-reference sample is determined using a control panel level derived from a tissue form similar to that derived from an individual biological sample. Furthermore, it is preferred to use any standard method known in the art for using the standard value of the degree of expression of the VANGL1 gene in the group of known disease stages. For example, the mean +/_2 standard deviation or the mean +/_3 standard deviation can be used as the standard value. In the context of the present invention, the degree of control group determined from a biological sample known to be non-cancer is referred to as a "normal control group level. On the other hand, the degree of control group is determined from the biological tissue of a cancer, which means For the degree of cancer control 69 201211250. The difference between the degree of expression of the sample and the extent of the control group can be standardized to control the degree of expression of the nucleic acid, for example, the housekeeping gene is not different depending on the degree of cancer and non-cancerousity of the cell. Exemplary control genes include, but are not limited to, beta-actin, glyceraldehyde-3-phosphate dehydrogenase, and riboprotein P. The degree of expression of the u-gene is increased or similar/equal to the extent of the cancer control group, and the individual can be diagnosed as having cancer to be treated. The invention also provides (i) a method of diagnosing whether a subject has a cancer to be treated, and/or (ii) an individual selecting a cancer treatment, the method comprising the steps of: determining the degree of performance of the VANGU in the cell or tissue, The cells or tissues are obtained from individuals suspected of having cancer to be treated; b) the degree of performance of VANGL1 compared with the normal control group; 〇 if the degree of expression of VANGL1 is increased compared with the degree of the normal control group, then the individual is diagnosed as having The cancer to be treated; and d) if the individual is diagnosed as having the cancer to be treated in step c), then the individual to be treated for cancer is selected. Alternatively, the method comprises the steps of: a) determining the degree of expression of VANGL1 in the cell or tissue, the cell or tissue obtained from the individual suspected of having the cancer to be treated; b) comparing the degree of performance of VANGL1 with the cancer control group; 201211250 C) If the degree of performance of VANGLl t is similar or equal to the degree of cancer control, then the diagnostic material has the cancer to be treated; and d) if one is diagnosed as having the disease to be treated in step c), then cancer is selected The individual being treated. The present invention also provides a diagnostic kit for diagnosing or determining the efficacy or applicability of a cancer that is suspected of being subjected to a cancer that can be treated with the VANGU multipeptide of the present invention. Useful in the middle. Preferably, the cancer includes, but is not limited to, bladder cancer, breast cancer, cervical cancer, cholangiocarcinoma, endometriosis, liver cancer, non-small cells: carcinoma, osteosarcoma, smear cancer, small cell lung cancer and acute Myeloid leukemia. More particularly, the kit preferably includes at least one reagent for measuring the degree of expression of the VANGL1 gene from an individual cell, the reagents being selected from the group: (a) a reagent for detecting the VANGL1 gene. mRNA; () ° agent for detecting VANGL1 protein or immunologically active fragment thereof; and (c) a reagent for detecting biological activity of VANGU protein. suitable. Examples of the reagent for detecting the mRNA of the VANGL1 gene may include a nucleic acid which specifically binds or recognizes VANGL1 mRNA, for example, an oligonucleotide having a sequence complementary to a portion of VANGL1 mRNA. These kinds of oligonuclei can be prepared by using the primers and probes of VANGU Gangren as an example. These kinds of oligonucleosides can be prepared according to methods well known in the art, and reagents for detecting VANGL1 mRNA can be used. Immobilized on a solid matrix. In addition, more than one reagent used to make 71 201211250 mRNA can be included in the kit. In another aspect, an example of a suitable reagent for detecting a VANGL1 protein or an immunologically active fragment thereof can include an antibody against a VANGL1 protein or an immunologically active fragment thereof. The antibody may be single or multiple plants. Furthermore, any fragment or modification of an antibody (eg, chimeric antibody, scFv, Fab, F(ab') 2, ρν, etc.) can be used as an agent as long as the fragment or modified antibody is maintained against VANGL1 The binding ability of the protein or its immunologically active tablet. Methods of preparing these classes of antibodies for protein detection are well known in the art, and any method can be used in the present invention to prepare such antibodies and their equivalents. Alternatively, it is possible to generate 5 sub-labels of antibodies via direct ligation or __ indirect labeling techniques. The method of labeling tfe and labeling antibodies and <study the binding of antibodies to their targets. It is well known in the art and any of the methods and methods can be used in the present invention. In addition, more than one reagent for the detective "ANGU I white matter can be included in the kit. The kit can contain more than one of the foregoing reagents. Set... Ash ~ J Ο Ο Γώ Combine the probe for the L1 gene or the solid substrate and reagent for the difficult peptide, the medium and container for culturing the cells, the positive control group reagent and the detection for Secondary of antibodies to Xia (4): for example, 'groups obtained from individuals without cancer or suffering from cancer or not = as a useful control group reagent. The kit of the present invention may further comprise, other materials required by the user's angle, including buffer solutions, diluents: for example: syringes and packaging inserts with operational instructions for use, tapes or ._, etc.). These reagents or such 72 201211250 are kept in a container with a logo. A suitable bottle (vial) and test tube. Ronggu pirates include bottles, small slopes of glass or plastic. a material that is diversified, for example, in one embodiment of the invention, a winter scorpion, a stalking agent is an agent against VANGL1 mRNA that can be immobilized on a solid substrate, for example - porous: including a plurality of positions, Each containing - nucleic acid (probe) - 2 can have a negative and/or positive control group position. Alternatively, the location of the control group is located in one of the strips separated from the test strip. Depending on the need, different detection bits = containing a different amount of immobilized nucleic acid 'ie a higher amount in the first detection position - lower content in subsequent positions. By the addition of the test sample, some locations of the non-signalable signal provide a quantitative indication of the amount of the sample. The integrated measurement position can be placed in any suitable detectable shape and is generally in the shape of a strip or point across the width of a test strip. The kit of the present invention may further comprise a positive control group sample or a VANGU standard sample. The positive control group samples of the present invention can be prepared by collecting positive samples of VANGL1 and then analyzing their VANGU extent. Alternatively, purified VANGL1 protein or polynucleotide can be added to cells that do not exhibit VANGU to form a positive sample or a VANGU standard sample. In the present invention, purified VANGL1 can be a recombinant protein. The degree of VANGL1 of the positive control group sample is, for example, greater than the critical value (cut 〇 ff 丨 丨 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 The ability to recognize an antibody of the invention or fragment thereof 73 201211250. Examples of partial peptides of the invention include polypeptides which are at least 8, preferably 15, more preferably in the amino acid sequence of the protein of the invention. Composition of 20 contiguous amino acids. The use of one of the proteins of the invention or a peptide (polypeptide) can diagnose a cancer by detecting one of the antibodies (eg, blood, tissue). The method of protein and peptide is as described above. As described above, the method for diagnosing cancer of the present invention can be carried out by measuring the difference between the amount of the anti-VANGL1 antibody and its corresponding control group. If the cell or tissue of the individual contains an antibody The gene expression product (VANGU) antibody and the amount of the anti-VANGL1 antibody were determined to be greater than the cut-off value in the extent of its normal control group, the individual was suspected of suffering from cancer. In one embodiment, the diagnostic kit of the present invention may comprise a victory of the present invention and an HLA molecule bound thereto. A method of detecting an antigen-cytotoxic T lymphocyte using an antigen peptide and an HLA molecule has been established (for example,

Altman JD a/., Science. 1 996, 274(5284): 94-6) 〇 Therefore, the complex of the peptide of the present invention and the HLA molecule can be applied to detect tumor antigen-specific cytotoxic T lymphocytes. Detection methods, thereby making it possible to relapse and/or metastasize early cancer. Further, it can be used for screening of an individual suitable for a drug comprising the peptide of the present invention as an active ingredient, or an evaluation of the therapeutic effect of the drug. A1 tman et al., for example, can prepare radiolabels such as tetramers. Accompanying, in particular, according to known methods (see, for example

Science. 1996, 274(5284): 94-6), an oligomeric complex of an HLA molecule with a peptide of the invention, 74 201211250 The use of a retanning can perform a diagnosis, for example by peripheral blood from an individual suspected of suffering from cancer Antigen-peptide specific cells in the peripheral blood lymphocytes were quantified. The present invention further provides diagnostic reagents for assessing immune responses by using the peptide epitopes described herein. In one embodiment of the invention, the HLA-A2 restricted peptide as described above is used as a formula for evaluating or predicting an immune response in a body. The immune response to be assessed by § can be induced by contacting the immune antigen (丨mmun〇gen) with immunocompetent/;? p/fo or /λ r/iro. In a preferred embodiment, immunocompetent cells for assessing an immune response are selected from peripheral blood, peripheral blood lymphocytes (PBL), and peripheral blood mononuclear cells (pBMC). Methods of collecting or isolating such immunocompetent cells are well known in the art. In some embodiments, any agent that results in the production of antigen-specific cytotoxic T lymphocytes can be used as a reagent' and cytotoxic T lymphocytes recognize and bind to a peptide epitope. The peptide reagent may or may not be used as an immunizing antigen. Analytical systems for such assays include fairly recent technological developments such as tetramers' staining of lymphocytes and interferon release assays or EL I SPOT assays. In a preferred embodiment, the immunocompetent cells to be contacted with the peptide test agent can be antigen presenting cells, including dendritic cells. For example, the peptide of the present invention can be used for tetramer staining analysis to evaluate peripheral blood mononuclear cells in the presence of antigen-specific cytotoxic T lymphocytes after exposure to tumor antigens or an immune antigen. HLA tetramer complex 75 201211250 can be used to directly visualize antigen-specific cytotoxic lytic lymphocytes (see, for example, Ogg 3, Science 279: 21 03-21 06, 1 998; and Altman ei W, Science 1 74 : 94-96, 1 996 ), and the frequency of antigen-specific cytotoxic T lymphocyte populations in samples of peripheral blood mononuclear cells. A tetramer reagent using the peptide of the present invention can be produced as follows. The peptide that binds to HLA is refolded in the presence of the corresponding HLA heavy chain and cold 2-microglobulin to produce a three molecule complex. In the complex, the carboxy terminus of the heavy chain is biotinylated at a pre-designed location into the protein. The avidin is then added to the complex to form a tetramer composed of a tri-molecular complex and streptavidin. The tetramer can be used to stain the antigen for cell expression by fluorescently labeling avidin. The cells can then be identified, for example by flow cytometry. Such analysis can be used for diagnostic and prognostic purposes. Cells determined by this procedure can also be used for therapeutic purposes. The invention also provides reagents for assessing immune recall responses (see, for example, Bertoni etaL, J Clin)

Invest. 1 00: 503-51 3, 1 997 174: 1565-1570, 1991), which comprises the peptide of the present invention. For example, for the presence of antigen-specific cytotoxic T lymphocytes, a patient-specific PBmc sample from an individual having a cancer to be treated can be analyzed using a specific specific peptide. A sample of the human-containing liquid containing the monocytes can be evaluated by culturing the PBMC and stimulating the cells with the peptide of the present invention. The expanded cell population is analyzed after a suitable culture period, for example for cytotoxic lymphocyte activity. 76 201211250 The peptide can also be used as a reagent to evaluate the efficacy of a vaccine. PBMC obtained from a patient vaccinated with one immunogen can be analyzed using, for example, the above method. The patient is HLA-typed and selected to identify the peptide antigen reagents that are present in the patient's allele specific molecule for analysis. By virtue of the presence of the epitope-specific cytotoxic tau lymphocytes in the pBMc sample, the immunogenicity of the field can be indicated. The peptide of the present invention is also used to produce antibodies using techniques well known in the art (see, for example, CURRENTPR〇T〇C〇lsinimmun〇l〇gy,

Wiley/Greene, NY; and Antibodies A Ub〇rat〇ry Manual,

Harlow and Lane, Cold Spring Harbor Laboratory Press, 1 9 8 9 ), which is effective as a reagent for diagnosing or monitoring cancer. Such antibodies may include those that recognize peptides that endure HLA molecular content, i.e., antibodies that bind to the peptide-MHC complex. The peptide or composition of the invention has some additional uses, some of which are described herein. For example, the invention provides a diagnosis or detection of a disease characterized by the performance of a VANGU immunoreactive peptide. These methods comprise assaying the performance of a VANGL1 HLA-binding peptide in a biological sample or a complex of a VANGL1HLA-binding peptide with an HLA class! molecule. The performance of a peptide or the complex of a peptide and an HLA class! molecule can be determined or detected by analysis of a binding partner for a peptide or complex. In a preferred embodiment, the binding partner for the peptide or complex is an antibody that recognizes and specifically binds to the peptide. The performance of VANGL1 in a biological sample, such as a tumor slice, can also be tested by using the standard PCR amplification step of the VANGL1 primer. Examples of tumor manifestations are presented and demonstrated herein. 77 201211250 The conditions for amplification of VANGL1 and the further advancement of the primers can be found in W02003/27322. Preferably, the diagnostic method comprises contacting a biological sample isolated from a body with one of the reagents specific to the VANGL1 HLA binding peptide to detect the presence of the VANGL1 HLA binding peptide in the biological sample. As used herein, "contacting" means placing a biological sample in an effective proximity reagent and under suitable conditions (eg, concentration, temperature, time, ionic strength) to allow for the combination of the reagent with the VANGL1 HU present in the biological sample. The specific interaction of peptides. Generally, the conditions for contacting a reagent with a biological sample are those familiar to those skilled in the art to promote cognate between the molecule and the biological sample (eg, a protein and its receptor congener, The specific interaction between the antibody and its protein antigen congener, a nucleic acid and its complementary sequence congener. Demonstration conditions that promote specific interactions between molecules and their congeners are described in the I $ proposed by L〇w et d

Patent No. 5, 1〇8, 921. The diagnostic method of the present invention can be performed in "either one or both. Thus, in the present invention, the biological sample can be located in - for example, the biological sample can be an i./2 F/叩 tissue and is specific to VMGL1 immunity. Reactive peptide peptide reagents can be used to detect the presence of such molecules in tissues. Alternatively, (10) collecting or isolating biological samples (eg, blood samples, tumor sections, tissue extracts). In an embodiment, the biological sample may be a cell-containing sample, more preferably the same as the tumor cells collected from the individual to be & broken or tested. Alternatively, the diagnosis may be performed by a method by using fluorescence Prime 78 201211250

(fluorescein) labeling of HLA polyplexes allows direct quantification of antigen-specific cells (eg, A11man, J. D. e ί a, 1 9 9 6, Science 274: 94; Altman, JD et al. , 1993, Proc. Natl. Acad. Sci. USA 90 : 1 0330 ). Intracellular lymphokines staining and interferon release assays or ELISPOT assays have also been provided. Tetramer staining, intracellular lymphokine staining, and ELI SPOT analysis were all shown to be at least 10 times more sensitive than general analysis (Murali-Krishna, K. et al., 1998, Immunity 8: 177; Lalvani, A. et al., 1 997 J. Exp. Med. 186: 859; Dunbar, PR et al., 1 998, Curr. Biol. 8: 413). Pentamers (e.g., US 2004-209295A), dextramers (e.g., WO 02/072631), and streptamers (e.g., Nature medicine 6-631-637 (2002)) can also be used. For example, 'in some embodiments' the invention provides a method of diagnosing or assessing an immune response in an individual administered to at least one VANGL1 peptide of the invention, the method comprising the steps of: (a) stimulating the cytotoxicity of a cell suitable for inducing specificity to the immunogen The immunogen is contacted with the immunologically active cells under conditions of a τ lymphocyte; (b) detecting or determining the degree of induction of the cytotoxic tau lymphocytes induced in step (a); and (c) immunizing the individual The response is correlated with the degree of induction of cytotoxic lytic lymphocytes. In the present invention, the immunogen is (a) a VANGL1 peptide selected from the amino acid sequence of sequence identification numbers: 1 and 3 to 67, a peptide having such an amino acid sequence 79 201211250, and having such a peptide The amino acid sequence is at least one of the morphs modified therein by substitution with 2 or more amino acids. Conditions suitable for inducing immunogenic specific cytotoxic tau lymphocytes during the period are well known in the art. For example, immunocompetent cells can be cultured in Vi tro to induce immunogen-specific cytotoxic T lymphocytes in the presence of immunity. To induce immunogenic cytotoxic T lymphocytes, any stimulating factor can be added to the cell culture. For example, IL-2 is a preferred stimulator for cytotoxic tau lymphocyte induction. In some embodiments, the step of monitoring or assessing the immune response of an individual to be treated with a peptide cancer can be performed before, during, and/or after treatment. In general, in the course of cancer treatment, the immunogenic peptide is repeatedly administered to the individual to be treated. For example, an immunogenic peptide can be administered weekly for 3-10 weeks. Thus, an individual's immune response can be assessed or monitored during the cancer treatment procedure. Or the step of assessing or monitoring cancer treatment can be done at the completion of the treatment procedure. According to the present invention, the induction of the enhanced immunogen-specific cytotoxic T lymphocytes indicates that the individual to be evaluated or diagnosed immunologically responds to the administered immunogen when compared with the control group. A suitable control set for assessing an immune response includes, for example, when the immunocompetent cells are not in contact with the peptide or with a control group having an amino acid sequence other than any VANGL1 peptide (eg, a random amino acid sequence) The degree of induction of cytotoxic T lymphocytes upon exposure. In a preferred embodiment, the individual's immune response is assessed in a sequence-specific manner by comparing the immune responses between the individual immunogens administered to the individual. In particular, even when a mixture of some species of VANGL1 peptide of 80 201211250 m is administered to an individual 眭 A ^ ^ ^ ’, the immune response according to the peptide can be diversified. In this example, by JJ Xuanren & A, Yatian compared the immune responses between the individual peptides, and confirmed that the peptides were not significantly higher in response to one of them. XI. Antibodies The invention provides antibodies which bind to the peptides of the invention. Preferably, the antibody binds specifically to the peptide of the present invention and does not bind (or weakly bind) i to the peptide of the present invention. Alternatively, the antibody binds to the peptide of the invention and its homologs. The antibody against the peptide of the present invention can be used for cancer diagnosis and prognosis analysis and imaging methods (imaging me1; h〇d〇l〇gies). Similarly, such antibodies may provide for the treatment, diagnosis, and/or prognosis of other cancers for the extent that VANGL1 is also exhibited or overexpressed in % of cancer patients. In addition, antibodies that are expressed intracellularly (eg, 'single-chain antibodies') can be treated in

VANGL1 is therapeutically effective in cancer-related manifestations. Examples of cancers associated with the performance of VaNGU include, but are not limited to, sputum cancer, breast cancer, cervical cancer, cholangiocarcinoma, endometriosis, liver cancer, Non-small cell lung cancer, sarcoma, pancreatic cancer, small cell lung cancer and acute myeloid leukemia. The present invention also provides various immunological activity assays for the detection and/or quantification of VANGL1 protein (eg, Sequence ID: 69) or its fragment, VANGL1 protein (eg, 'SEQ ID NO: 69) or fragments thereof including free selection An amino acid sequence consisting of the amino acid sequence of the group consisting of sequence identification numbers 1 and 3 to 67. & class analysis can include one or more anti-VANGL1 antibodies that recognize and bind to the VANGU protein or fragment thereof as appropriate 81 201211250. In the context of the present invention, an anti-VANGL1 antibody that binds to a VANGL1 polypeptide is preferably a multi-peptide that is identified as a group having a free sequence identification number: 1 and 3 to 67. Amino acid sequence. The binding specificity of the antibody can be confirmed by an inhibition test. It is, in the presence of any fragment of the peptide having the amino acid sequence selected from the sequence identification numbers: 1 and 3 to 67, when the binding between the antibody to be analyzed and the full-length VANGL1 peptide is Upon inhibition, it shows that this antibody binds specifically to the fragment. In the context of the present invention, 'including, but not limited to, radio-immunoassays, immuno-chromatgraph techniques, enzyme-linked immunosorbent assays (ELISA), enzymes Such immunoassays are performed in a variety of immunoassay formats well known in the art, such as enzyme- 1 inked i_unofluorescent assays (ELIFA). The immunological but non-antibody analysis of the present invention may also include a T cell immunogenic assay (inhibition or stimulation) and a major histocompatibility complex (MHC) binding assay. Furthermore, the invention also encompasses immunoimaging assays having the ability to detect cancers that exhibit VANGL1, including, but not limited to, radioimaging imaging using the labeled antibodies of the invention. Such analysis can be clinically useful in the detection, monitoring and prognosis of cancer in vaNGL1, VANGL1 manifests in cancer, including, but not limited to, bladder cancer, breast cancer, cervical cancer, cholangiocarcinoma, endometriosis Disease, liver cancer, non-small cell lung cancer, osteosarcoma, sputum cancer, small 82 201211250 cell lung cancer and acute myeloid leukemia. The invention provides antibodies that bind to the peptides of the invention. The antibody of the present invention is used in any of the open formulas, such as single or multiple strains of antibodies, and includes obtaining from the animal, for example, $ | , , _!_# J, such as devils, with the peptide of the present invention. Immunized antiserum, multi-strain or monoclonal antibodies of all types, human antibodies, and humanized antibodies produced by genetic recombination. The peptide of the present invention which is used as an antigen to obtain an antibody may be derived from any animal species 'but preferably from a mammal, for example, a human, a mouse or a large one, more preferably a human. Human derived peptides are available from the nucleotide or amino acid sequences disclosed herein. According to the present invention, the peptide used as an immunizing antigen can be a complete egg white or a partial peptide protein f. The partial peptide may include, for example, an amine (N) terminal or a carboxyl (C) terminal fragment of one of the peptides of the present invention. Here, an antibody is defined as a protein which reacts with the full length or fragment of the VANGU peptide. In a preferred embodiment, the antibody of the invention recognizes a VANGL1 fragment peptide having an amino acid sequence selected from the group consisting of: 1 and 3 to 67. The method for synthesizing oligopeptides is well known in the art. After synthesis, after use as an immunizing antigen (immun〇gen), the peptide can be purified as needed. In the present invention, an oligopeptide (e.g., 9 or 10 members) can be bound or linked to a carrier to enhance immunogenicity. Keyhole-limpet hemocyanin (KLH) is well known as a carrier. Methods for binding keyhole limpet hemocyanin and peptides are well known in the art. Alternatively, a gene encoding a peptide of the present invention or a fragment thereof can be inserted into a known expression vector, which is then transformed into a host cell as described in 83 201211250. The desired peptide or fragment thereof can be recovered from the outside or inside of the host cell by any standard method and can be used as an antigen thereafter. Alternatively, the entire cell expressing the peptide or its cell extract or a chemically synthesized peptide can be used as an antigen. Any mammal can be immunized with an antigen, but it is preferred to consider compatibility with the parental cells used for cell fusion. In general, Rodentia, Lag〇m〇rpha or primate are used. Animals of the caries include, for example, mice, rats, and hamsters. Rabbit-shaped animals include, for example, rabbits. Primate animals include, for example, the narrow-nose (old world monkey) monkeys, such as the Macacafascicuiaris, rhesus monkey, sacred bab〇〇n, and chimpanzees. Methods are well known in the art. The intraperitoneal cavity of the antigen; the main injection (intraperit〇neai injecti〇n) or subcutaneous injecti〇n is a standard method for immunizing mammals. More specifically, the antigen may be diluted or suspended in a suitable amount of phosphate buffer, physiological saline or the like. If desired, the antigen suspension can be mixed with a suitable amount of a standard adjuvant such as Freund's complete adjuvant (Freund, sc〇n) piete adjuvant to prepare an emulsion (emulsi〇n) and then administered to breastfeeding animal. Preferably, it is administered after 4 to 2 days of antigen mixed with a suitable amount of Freund's incomplete adjuvant. A suitable vector can also be used for immunization. After the above immunization, serum can be tested by standard methods in order to increase the amount of antibody required. The polyclonal antibody against the peptide of the present invention can be prepared by collecting blood from the immunologically mobilized 84 201211250 which is tested to increase the desired antibody in the serum and by separating the serum from the blood by any general method. A plurality of antibodies include a fraction of a plurality of antibodies isolated from blood 'green' containing a plurality of antibodies. For example, the use of an affinity column in combination with the peptide of the present invention and further purification of this portion using Protein A or Protein G columns allows for the purification of partially purified immunoglobulin G or guanidine from only the peptide of the present invention. In order to prepare a monoclonal antibody, as described above, the mammalian cells are collected from the mammals which have been immunized with the antigen and confirmed to have an increased degree of the desired antibody in the blood, and the immune cells are subjected to cell fusion. The immune cells used for cell fusion are preferably obtained from the spleen. Other parental cells to be fused with the above-described immune cells include, for example, 'my e 1 〇ma' of a mammal, and preferably myeloma cells having acquired characteristics of the drug-selected fused cells. According to known methods, such as Milstein et ai. (Galfre and

Milstein, Methods Enzymol 73: 3-46 (1 981)), which fuses the above immune cells with myeloma cells. Fusion tumors obtained from cell fusion by culturing them in standard screening media, such as HAT medium (medium containing hypoxanthine, amin0pterin, and thymidine) Being screened. The cells are usually maintained in HAT medium for several days to several weeks for the death of other cells (non-fused cells) other than the desired fusion tumor. Thereafter, standard limiting dilutions are performed to screen and replicate the fusion tumors that produce the desired antibodies. In addition to the above method in which a non-human animal is immunized with an antigen in order to prepare a fusion tumor, a peptide, a peptide-expressing cell or a cell extract thereof can be obtained, and the human lymphocyte is infected, for example, by an eb virus. Those ones. The human antibody required to combine the immunized lymphocytes with a myeloma derived from humans with unclear cleavage ability, such as U266, to produce a fusion of the desired human antibody can be combined with a peptide that can be obtained. (Unexamined Published Japanese Patent Application No (JP-A) Sho 63-17688). The obtained fusion tumor was transferred into the abdominal cavity of the mouse and ascites was extracted. The obtained monoclonal antibody can be purified by, for example, ammonium sulfate precipitation, a protein A or protein G column, DEAE ion exchange chromatography or an affinity column coupled to the peptide of the present invention. The antibody of the present invention can be used not only to purify and detect the peptide of the present invention, but also as a promoter and antagonist of the peptide of the present invention. Alternatively, an antibody-producing immune cell, such as an immunized lymphocyte, can be immortalized by a consensus oncogene and used to prepare a monoclonal antibody. Genetic engineering techniques can also be used to recombinantly prepare the individual antibodies thus obtained (see, for example, Borrebaeck and Larrick, Therapeutic

Monoclonal Antibodies, published in the United

Kingdom by MacMillan Publishers LTD (1 990)). For example, a DNA encoding an antibody can be replicated from an immune cell, e.g., one of the antibody-producing fusion tumors or an immunized lymphocyte, inserted into a suitable vector' and introduced into a host cell to produce a recombinant antibody. The present invention also provides a recombinant antibody prepared as described above. Further, the antibody of the present invention may be a fragment of an antibody or a modified antibody as long as it binds one or more of the peptides of the present invention. For example, antibody fragment 86 201211250 can be Fab, F(ab')2, Fv or single-chain Fv (scFv), in which Fv fragments from heavy and light chains are joined by a suitable linker (Hust〇fi occupies

Proc Natl Acad Sci USA 85: 5879-83 (1 988)). More specifically, antibody fragments can be produced by treating the antibody with an enzyme such as papain or pepsin. Alternatively, the gene encoding the antibody can be constructed, inserted into a expression vector and expressed in a suitable host cell (see, for example, J Immunol 152: 2968-76 (1994); Better and Horwitz, Methods Enzymol 178: 476- 96 (1989); Pluckthun and Skerra, Methods Enzymol 178: 497-515 (1989); Lamoyi, Methods Enzymol 121: 652-63 (1986); Rousseaux et al., Methods Enzymol 121: 663-9 (1986); Bird And Walker, Trends Biotechnol 9: 132-7 (1991)). The antibody can be modified by binding to various molecules, such as polyethylene glycol (p〇lyethylene g 1 y co 1, PEG). The present invention provides such modified antibodies. A modified antibody can be obtained by chemically modifying an antibody. These methods of modification are common in the art. Or 'the antibody of the invention can be obtained as a chimeric antibody, between a variable region derived from a non-human antibody and a fixed region derived from a human antibody, or a humanized antibody, including a complementarity determining region derived from a non-human antibody , the framework work region (FR) and the fixed region from human antibodies. Such antibodies can be prepared according to known methods. Humanization can be performed by substituting the sequence of the rodent complementarity determining region for the complementary sequence corresponding to the human antibody (see, for example,

Verhoeyeri takes a/., Science 239:1 534-1 536 (1 988)). Thus, such humanized antibodies are chimeric antibodies in which a human variable region that is substantially less than intact 87 201211250 has been replaced by a corresponding sequence from a non-human species. Whole human antibodies including human variable regions in addition to the framework and fixed regions can also be used. Such antibodies can be produced using a variety of techniques known in the art. For example, the i n v i tro method includes the use of a recombinant library of human antibody fragments presented on phage (e.g., H00genb00m &

Winter, J. Mol. Biol. 227:381 (1 991 )). Similarly, human antibodies can be made by introducing a human immunoglobulin locus (1 〇 C i ) into a transgenic animal, such as a mouse in which the endogenous immunoglobulin gene has been partially or completely deactivated. This method is described as 'for example, U. s. P atent N 〇s. 6, 1 50, 584, 5, 545, 807; 5, 545, 806; 5, 569, 825; 5, 625, 126; 633, 425; 5, 661,016. The antibodies obtained from the above can be purified to homogeneity (h〇mogeneity). For example, isolation and purification of antibodies can be performed according to methods for isolation and purification of general proteins. For example, by suitable selection and binding column chromatography, for example, affinity tube, filtration, ultrafiltration, salting out, dialysis, sodium polydodecyl sulfate electrophoresis (SDS polyacrylamide gel) The use of electrophoresis and isoeiectric f〇cusing can separate and isolate antibodies (Antibodies: A Laboratory Manual. Ed Harlow and David Lane, Cold Spring Harbor Laboratory (1 988)), but is not limited thereto. The protein a column and the protein G column can be used as an affinity column. The exemplary protein A column to be used includes 'for example, Hyper D, P0R0S and Sepharose FF (Pharmacia) ° In addition to affinity 'exemplary chromatographic analysis including, for example, ion exchange chromatography 88 201211250 knife analysis hydrophobic layer analysis, colloid Strategy, Reverse Chromatography, Adsorption Chromatography, etc. (Strategies for Protein Purification and Characterization: A Laboratory Course Manual. Ed Daniel R. Marshak et al., Cold Spring Harbor Laboratory Press (1 996)). The chromatographic analysis step can be performed by liquid chromatography, such as jjpLC and FPLC. For example, the measurement of absorption, enzyme-linked immunosorbent assay (ELISA), enzyme immunoassay (EIA), radioimmunoassay, and/or immunofluorescence can be used to measure the antigen-binding activity of the antibody of the present invention. In an enzyme-linked immunosorbent assay, the antibody of the present invention is immobilized on a culture plate, providing the peptide of the present invention to a culture plate, and then providing a sample containing the desired antibody, such as a culture suspension of the antibody-producing cells or Purified antibody. Thereafter, a second antibody which recognizes the antibody and is labeled as an 'enzyme, such as an invertase, is cultured, and then the plate is cultured. Next, after washing, an enzyme substrate, such as p-nitrophenyl ph〇sphate, was added to the culture plate, and absorption was measured to evaluate the antigen binding activity of the sample. A fragment of a peptide, such as a c-terminal or N-terminal fragment, can be used as an antigen to evaluate antibody binding activity. According to the present invention, BIAcore (Pharmacia) can be used to assess the activity of an antibody. The above method allows the detection or measurement of the peptide of the present invention by exposing the antibody of the present invention to a sample presumed to contain the peptide of the present invention and prescribing or measuring the immune complex formed by the antibody and the triumph. Since the peptide detection or measurement method according to the present invention can specifically detect or measure the peptide, the method can be useful in various experiments using the peptide. 89 201211250 x π. Vector and host cells The present invention also provides vectors and host cells in which nucleotides encoding the peptides of the present invention are introduced. The vector of the present invention is effective for maintaining the nucleotide of the present invention, particularly DNA in a host cell to express the peptide of the present invention, or to administer the nucleotide of the present invention for gene therapy. When E. coli is a host cell and the vector is amplified and produced in large quantities in E. coli (eg, JM109, DH5 alpha, HB101 or XLlBlue), the vector should have "〇ri" to be amplified in E. coli. Screening for the tt, gene of the transformation E · c 01 i (for example, by, for example, ampicillin, tetracycline, kanamyci, chloramphenicol or the like The drug is screened for one of the drug resistance genes). For example, an M13_series vector, a pUC_ series vector, pBR322, pBluescript, pCR-Script, or the like can be used. In addition, pGEM-T, pDIRECT and pT7 can also be used for secondary replication and extraction of cdna with the above vectors. A performance vector is particularly effective when the vector is used to produce a protein of the invention. For example, one of the expression carriers to be represented in E. c〇丨i should have the above characteristics to be magnified in E. coli. When ec〇li, such as JM109, DH5 alpha, HB101 or XLlBlue, is used as the host cell, the vector should have a promoter, such as the lacZ promoter (Ward et aj., Nature 341: 544-6 (1989); FASEB J 6: 2422-7 (1 992)), araB promoter (Better 5/., Science l〇41 3 (1988)), T7 promoter or analog, which can effectively express the desired gene in E. col i • in. Based on that aspect, for example, 90 201211250 pGEX-5X-l (Pharmacia), "QIAexpress system" (Qiagen), pEGFP and pET (in this case, the host is preferably BL21, which expresses T7 RNA polymerase) can be used. Replace the above carrier. Alternatively, the vector may contain a signal sequence for peptide secretion. An exemplary signal sequence that directs the peptide to be secreted to the inter-plasma of E col i is the peiB signal sequence (Lei et al., J Bacteriol 1 69: 4379 (1 987)). The manner in which the vector is introduced into the host cell of interest includes, for example, a chlorination method, and an electroporation method. In addition to E. co 1 i 'eg expression vectors from mammals (eg pcDNA3 (Invitrogen) and pEGF-BOS (Nucleic Acids Res 18(17): 5322 (1990)), pEF, pCDM8), expression vectors from insect cells (eg, "Bac-to-BAC baculovirus expression system" (GIBCO BRL), pBacPAK8), plant-derived expression vectors (eg 'pMjji, pMH2), expression vectors from animal viruses (eg , pHSV, pMV, pAdexLcw), expression vector from retrovirus (eg, pZipneo), expression vector from yeast (eg, "Pichia Expressi〇n Kit" (Invitrogen), pNVl SP-QOi) and from the grass A performance vector of Baci i lus subti 1 is (for example, pPL6〇8, pKTH5〇) can be used to produce the multi-peptide of the present invention. In order to be in animal cells, such as CH0, COS or NIH3T3 cells, the expression vector 'vector should have a promoter necessary for expression in such cells' such as the SV40 promoter (Mulligari et al., Nature 277: 1 08 (1979)) , MMLV-LTR promoter, EF1 alpha promoter (Mizushima 91 201211250 et al. 'Nucleic Acids Res 18: 5322 (1990)), CMV promoter, etc., and marker genes for screening transformants (eg by drug screening ( For example, neomycin, a drug resistance gene of G418 is preferred. Examples of known vectors having these vector characteristics include, for example, pMAM, pDR2, pBK-RSV, pBK-CMV, pOPRSV and p〇Pl3. The following examples are intended to illustrate and illustrate the invention, and are not intended to limit the scope of the invention in any way, and may be used in the practice or testing of the invention. Equivalent to the methods and materials described herein, but describing suitable methods and materials. The publications referred to in this specification are patents or patent applications. The contents are specifically referred to as references. In the event of a conflict, the description of the present invention including the definitions will be controlled. In addition, the 'materials, methods and examples are merely illustrative' and are not intended to be limiting. [Examples] Materials and Methods Cell Line T2 HLA A 0201% human β lymphoblastoid cell line and cow, African green monkey kidney cell line were purchased from ATCC. Candidates for peptides from VANGL1 were selected using the binding prediction software "BIMAS" (httP://www_bimas. Cit.nih.g〇v/mQibi〇/hia』ind) 92 201211250 (Parker et al. (J Immunol 1994, 152(1): 163-75),

Kuzushima et al. (Blood 2001, 98(6): 1872-81)) predicted 9 and 10 member peptides from VANGL1, which bind to HLA-A* 0201 molecules. These peptides were synthesized by Biosynthesis (Lewi svi 1 le, TX) according to a standard solid phase synthesis method and purified by reversed phase high performance liquid chromatography (HPLC). The purity (> 90%) and identity of these peptides were confirmed by analytical HLpc and mass spectrometry, respectively. The peptide was dissolved in dimethylsulfoxide (DMS0) at 20 mg/ml and stored at -80 t. //? Hi cell cytotoxic T lymphocyte induction Use dendritic cells derived from mononuclear leukocytes as antigen presenting cells to induce cellular toxic T lymphocyte responses against peptides expressed on human leukocyte antigen (HLA). For example, dendritic cells are produced as described elsewhere (Nakahara S et al., Cancer Res 2003 Jul 15, 63(14): 4112-8). In particular, peripheral blood mononuclear cells from a positive suspension volunteer (HLA-A* 0201 positive) were isolated from a Ficoll_piaque (pharmacia) solution and attached by attaching to a plastic tissue culture plate (Bect〇n Dickins〇n). To enrich it as a mononuclear white blood cell part. The population of enriched mononuclear white blood cells is cultured at 1〇〇〇u/ml of human granule-macrophage community stimulating factor (granul〇Cyteiacrophage c〇1〇ny_stimulating gm-csf) (r&d ^^^, with 1 〇〇〇u/ml of interleukin 93 201211250 (interleukin, IL)-4 (R&D System) in the presence of 2% heat deactivated self-preserved serum (aut〇l〇gous serum, AS) (Invitrogen). After 7 days of culture, each peptide was synthesized at 20 /zg/ml in the presence of 3 //g / ml of beta 2-microgl〇bul in AIM_V medium. Pulsed (pUise(j) cytokine-induced dendritic cells were 3 hrs at 3 rc. The resulting cells were shown to exhibit dendritic cell-associated molecules such as CD80, CD83, CD86 and HLA Class II on their cell surface (data not shown). The dendritic cells pulsed with these peptides were then deactivated by χ-ray (2〇Gy) and mixed with CD8-positive T cells in a ratio of 1:2 (), CD8-positive T cells by CD8

The Positive Isolation Kit (Dynal) is choosing to acquire. These cultures were placed in 48-well plates (Corning); each well contained 1.5 X 1 4 peptide-pulsed dendritic cells, 3 X 1〇5 CD8-positive T cells, and 10 ng/mi IL_7 (R&D System) Serum medium was obtained from 0.5 ml of AIM-V/2% itself. Three days later, the culture was added to IL-2 (CHIRON) to a final concentration of 20 IU/ml. On day 7 and day 14, dendritic cells with peptide peptides themselves were further stimulated by T cells. Dendritic cells were prepared each time in the same manner as described above. On day 21, after the third round of peptide stimulation, the cytotoxic T lymphocytes were tested for anti-peptide pulsed T2 cells (Tanaka H et al., Br J Cancer 2001 Jan 5, 84(1): 94 -9; Umano Y et al·» Br J Cancer 2001 Apr 20, 84(8): 1052-7; Uchida N et al., Clin Cancer Res 2 0 04 Dec 15, 10(24): 8577-86; Suda T et al., Cancer Sci 2006 May, 97(5): 411-9; Watanabe T et al., Cancer Sci 2005 Aug, 96(8): 94 201211250 498-506) ° Cytotoxic T lymphocyte expansion step Use and by Riddell et al. (Walter EA et al., N Engl J Med 1 995 Oct 1 9, 333(1 6): 1038-44; Riddell SR et al Nat Med 1996 Feb ' 2(2): 216- 23) A similar method of cloning expands cytotoxic T lymphocytes in culture. All 5 X 1 04 cytotoxic sputum lymphocytes were suspended in 25 ml of AIM-V/5% self-derived serum medium containing two human β-lymphocyte strains, deactivated by MMC, at 40 ng/ml - In the presence of CD3 monoclonal antibody (Pharmingen). One hour after the start of cultivation, '120 IU/ml of IL-2 was added to the culture. On day 5, 8, and 11 fresh serum cells were obtained from AIM-V/5% self containing 30 IU/ml of IL-2 (Tanaka H et al_, Br J Cancer 2001 Jan 5, 84 ( 1): 94-9; Umano Y et al., Br J Cancer 2001 Apr 20, 84(8): 1052-7; Uchida N et al., Clin Cancer Res 2004 Dec 1 5, 10(24): 8577- 86; Suda T et al., Cancer Sci 2006 May, 97(5): 411-9; Watanabe T et al., Cancer Sci 2005 Aug, 96(8): 498-506). The establishment of cytotoxic T lymphocyte replication was performed to dilute to have 〇. 3, 1 and 3 cytotoxic T lymphocytes/holes in a round-b〇ttomed micro-valence plate (Nalge Nunc I) Nternat i ona 1). Cytotoxic T lymphocytes and two human β-lymphocyte strains of 1 x 1 04 cells/well, 30 ng/ml anti-CD3 95 201211250 antibody and 125 ϋ/ml IL-2 in all 150 μ 1 /well was cultured in AIM-V medium containing 5% of the serum obtained by itself. After 10 days, 50 "1/hole IL-2 was added to the medium to achieve a final gradient of 125 U/ml IL-2. The activity of the cytotoxic T lymphocytes was tested on day 14 and the cytotoxic T lymphocyte replication was expanded using the same method described above (Uchida N et al., Clin Cancer Res 2004 Dec 1 5, 1 0 (24): 8577- 86; Suda T et al., Cancer Sci 2006 May, 97(5): 411-9;

Watanabe T et al., Cancer Sci 2005 Aug, 96(8): 498-506). Specific cytotoxic T lymphocyte activity To test specific cytotoxic T lymphocyte activity, IFN-r enzyme binding immunospot (ELISP0T) analysis was performed with IFN_T enzyme binding immunosorbent assay (ELISA). Specifically, T2 (1 X 1 〇 4 /well) of the peptide pulse is prepared as a stimulator cel 1 . The cultured cells were used as responder cells in 48 wells (resp〇nder ceiih performed IFN-r enzyme binding immunospot assay and iFN-r enzyme binding immunosorbent assay under the manufacturer's step. Strongly expressed target gene and HLA-A02 The establishment of any or both of the cells is amplified by PCR to encode the open reading frame or cDNA of the target gene. The PCR amplification product is cloned into a performance vector. Using Upofectamine 2000 (Invitr〇gen), according to the manufacturer's recommended procedure 96 201211250 The plastid was transfected into COS7, a target gene and HLA-A# 020 1 null cell line. Two days after transfection, the transfected cells were collected as versene (Invitrogen) and used as cytotoxic Target cells for T lymphocyte activity assay (5×104 cells/well). Results predicted from HLA-A02 binding peptide of VANGL1 la舆lb shows 9 members of HLA-A02 binding of VANGL1 in order of high binding affinity With 10 members of the peptide, a total of 67 peptides with potential HLA-A02 binding ability were selected and tested to determine the epitope peptide. Table 1 a Table la, 9-member win from HLA-A02 binding of VANGL1 Peptide Initial position amino acid sequence fractional sequence identification number 194 FLFVVSYWL 2000 1 189 LLVLIFLFV 1236 2 162 ILLIGTWAL 1008 3 187 ALLLVLIFL 1000 4 190 LVLIFLFVV 796 5 225 SLVDALLFI 541 6 118 FLGLLVFLT 457 7 120 GLLVFLTPI 337 8 474 GLRDGIVFV 274 9 183 FVFRALLLV 238 10 124 FLTPIAFIL 234 11 235 YLAIVLLEL 226 12 159 KLLILLIGT 222 13 458 WLSTQWRLV 109 14 423 ILQHLAFCI 103 15 230 LLFIHYLAI 98 16 201 WLFYGVRIL 69 17 97 201211250 451 LQYDKDRWL 53 18 294 LLTASKFRA 49 19 246 LQPMFTLQV 46 20 484 KCLDFSLVV 38 21 216 YQGIVQYAV 32 22 422 SILQHLAFC 32 23 181 RVFVFRALL 26 24 153 FISMAFKLL 26 25 489 SLVVNVKKI 24 26 219 IVQYAVSLV 24 27 161 LILLIGTWA 24 28 229 ALLFIHYLA 18 29 499 FIILSEEFI 18 30 155 SMAFKLLIL 15 31 56 LLGNDSTRT 13 32 514 FVLRLQSET 11 33 Table lb Table lb, from VANGL1 HLA-A02 binding 10 member peptide start position amino acid sequence fraction sequence identification number 188 LLLVLIFLFV 4572 34 189 LLVLIFLFVV 2457 35 110 YLGLTVASFL 540 36 151 GLFISMAFKL 458 37 230 LLFIHYLAIV 413 38 245 QLQPMFT LQV 264 39 124 FLTPIAFILL 187 40 481 FVLKCLDFSL 185 41 161 LILLIGTWAL 139 42 293 NLLTASKFRA 107 43 506 FIDPKSHKFV 97 44 400 SMARALQKYL 85 45 136 ILWRDELEPC 79 46 122 LVFLTPIAFI 73 47 485 CLDFSLVVNV 64 48 229 ALLFIHYLAI 58 49 160 LLILLIGTWA 46 50 112 GLTVASFLGL 41 51 474 GLRDGIVFVL 36 52 98 201211250 155 SMAFKLLILL 35 53 232 FIHYLAIVLL 31 54 422 SILQHLAFCI 31 55 183 FVFRALLLVL 30 56 153 FISMAFKLLI 25 57 450 TLQYDKDRWL 23 58 218 GIVQYAVSLV 22 59 473 NGLRDGIVFV 21 60 197 VVSYWLFYGV 20 61 491 VVNVKKIPFI 20 62 194 FLFVVSYWLF 14 63 178 DMPRVFVFRA 14 64 104 GLDCKRYLGL 13 65 266 SLGHLSIQRA 11 66 246 LQPMFTLQVV 11 67 The starting position is the number of amino acid residues from the N-terminus of VANGL1. The combined score is from "BIMAS". Predicted peptides from VANGL1, restricted by HLA-A* 0201, induced cytotoxic T lymphocytes. Cytotoxic T lymphocytes were generated for those peptides derived from VANGL1 according to the procedure described in Materials and Methods. The peptide-specific cytotoxic T lymphocyte activity was determined by IFN-7" enzyme binding immunospot assay (Fig. 1). Compared with the control group hole, the hole number #7 (a) stimulated by VANGU-A02-9-1 94 (sequence identification number: 1) is stimulated by VANGU-A02-9-235 (sequence identification number: 12). Hole number #3 (b) and hole number #6 (c) with VANGL1-A02-9-484C sequence identification number: 21) showed strong IFN-τ production. On the other hand, specific cytotoxic T lymphocyte activity was not determined by stimulation with other peptides already shown in Tables 1 a and 1 b, although those peptides have the potential to be associated with HLA-A * 0 2 0 1 Combines 99 201211250 activity. As a typical negative data, a specific cytotoxic T lymphocyte response was not observed from the peptide target cells stimulated with VANGU-A02-9-189 (SEQ ID NO: 2) (d). As a result, three peptides from VANGL1 were confirmed to have the potential to induce potent cytotoxic T lymphocytes. The cytotoxic τ lymphocyte cell line and replication of the anti-VANGL1-derived peptide were detected by IFN-τ enzyme-binding immunospot assay and stimulated with VANGL1-A02-9-1 94 (SEQ ID NO: 1). Hole number #7 (a) The cell enthalpy showing the activity of the peptide-specific toxic lymphocytes in the hole number #6 (b) stimulated by VANGL1-A02-9-484 (SEQ ID NO: 21) is expanded. Cytotoxic T lymphocyte cell lines were established by limiting dilution as described in the "Materials and Methods" section above. The cytotoxic T lymphocyte activity of those cytotoxic T lymphocyte cell lines was determined by IFN-τ enzyme-binding immunosorbent assay (circle 2). The cytotoxic T lymphocyte cell line showed a strong resistance to IF N-7 production by the target cell corresponding to the peptide pulse as compared to the target cell of the peptide-free pulse. In addition, cytotoxic T lymphocyte replication was established by limiting dilution from cytotoxic T lymphocyte cell lines, and cytotoxic T from target cells resistant to peptides was determined by IFN-7 enzyme-binding immunosorbent assay. Lymphocytic replication of IFN- r is produced. Strongly determined from cytotoxic T lymphocyte replication stimulated by VANGL A02-9-1 94 (SEQ ID NO: 1) (a) and VANGU-A02-9-484 (SEQ ID NO: 21) (b) The lFN-r is generated (Fig. 3). 100 201211250 Specific cytotoxic T lymphocyte activity assay against target cells expressing VANGL1 and HLA-A* 020 1 The cytotoxic T lymphocyte cell line established by replication-enhanced peptides and replication for identification of VANGL1 and The ability of the molecule to target cells. The cytotoxic T lymphocytic cell line promoted by the corresponding peptide was used to replicate the specific cell cytotoxic T lymphocyte activity of anti-C〇S7 cells, while the COS1 cells passed the full length of VANGL1 and HLA-A*. The 0201 gene was transfected (for a specific pattern of cells expressing the VANGL1 and hlA-A*020 1 genes). C0S7 cells were prepared as a control group by transfection with the full-length VANGL1 or HLA-A* 020 1 gene. The cytotoxic T lymphocyte cell line stimulated with VANGL1-A02-9-484 (SEQ ID NO: 21) in the 4th round showed strong cells against COS7 cells expressing both VANGL1 and HLA-A* 0201 Toxic T lymphocyte activity. On the other hand, no significant specific cytotoxic T lymphocyte activity was detected in the anti-control group. Therefore, these data clearly demonstrate that VANGL1-A02-9-484 (SEQ ID NO: 21) is endogenously treated and expressed on target cells with HLA-A* 0201 molecules and recognized by cytotoxic T lymphocytes. These results indicate that this peptide from VANGL1 is a cancer vaccine that is suitable for the treatment of tumor patients with VANGL1 expression. Homologous analysis of antigenic peptides was performed with VANGU-A02-9-1 94 (sequence identification number: 1), VANGU-A0 2-9-235 (sequence identification number: 12) and VANGL1-A02-9-484 101 201211250 ( Sequence ID: 21) Stimulated cytotoxic T lymphocytes showed significant and specific cytotoxic lytic lymphocyte activity. This result may be due to VANGL A02-9-194 C serial identification number: 1) 'VANGL1-A02-9-235 (sequence identification number: 12) and VANGU-A02-9-484 (sequence identification number: 21) The sequence is a matter of homology to a peptide derived from other molecules known to be sensitive to the human immune system. To rule out this possibility, homology analysis was performed for these peptide sequences that were searched for the BLAST algorithm (www.neb i.nlm.nih.gov/b last/blast_cgi), and the BLAST algorithm was used. No sequences were shown to show significant homology. The results of the homology analysis indicated that VANGL1-A02-9-194 (sequence identification number: 1), VANGL1-A02-9-235 (sequence identification number: 12) and VANGL1-A02-9-484 (sequence identification number: 21) The sequence is unique, and therefore only the possibility of reporting small, for our best knowledge, these molecules will increase the immune response in the unplanned for some unrelated molecules. Therefore, it was confirmed that the novel HLA-A* 0201 antigen from VANGL1 is located in the peptide and has been proved to be suitable for cancer immunotherapy. Industrial Applicability The present invention provides novel tumor-associated antigens, particularly from VANGu

A related disease, such as cancer, has an anti-tumor immune response and is useful for cancer. This tumor-associated antigen is effective as a tamarin peptide vaccine, and more particularly with VANGU is bladder cancer, breast cancer, cervical cervix 102 201211250 cancer, cholangiocarcinoma, osteosarcoma, pancreatic cancer, endometriosis, liver cancer, non- Small cell lung cancer small cell lung cancer and acute myeloid white are described in detail herein when describing the present invention and referring to specific embodiments thereof

The boundaries and scope are defined by the scope of the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 consists of a series of photographs (a) to (d) showing I{?N enzyme-binding immunity on cytotoxic lytic lymphocytes induced by peptides derived from VANGL1 Results of spot analysis (ELISp〇T). Compared with the control group, stimulated by VANGL1-A02-9-194 (sequence identification number: 1) in hole number #7 (a), stimulated by VANGL1-A02-9-235 (sequence identification number: 12) In the hole number #3 (b) and the VANGL1-A02-9-484C sequence identification number: 21), the cytotoxic τ lymphocytes stimulated in the hole number #6 (c) showed strong IFN-7&quot; produce. The squares on the holes in these photographs indicate that cells from the corresponding pores were expanded to establish a cytotoxic T lymphocyte cell line. In contrast, as a typical example of negative data, it did not detect a specific iFN_r from a cytotoxic T lymphocyte stimulated with VANGL1-A02-9- 1 89 (SEQ ID NO: 2) (d) . In the figure, "+,, indicates that FN_7 is produced against the target cell of the appropriate peptide pulse, and - indicates that IFN_7 is produced against the target cell not pulsed with any peptide. 0 103 201211250 Fig. 2 The series consists of lines (a) and (b), showing the results of IFN_r enzyme, 纟σ 〇 immunosorbent assay', and the results are sequentially displayed as VANGL1-A02-9-1 94 (sequence identification number: 丨) (a) and VAPiGLl_A02H84 (SEQ ID NO: 2ι) (1}) IFN-γ production by stimulated cytotoxic T lymphocyte cell line. The results showed that the cytotoxic T lymphocyte was established by stimulation with each peptide compared with the control group. The globular cell line showed strong and potent iIFN_r production. In the figure, ''+,, indicates that IFN_7 is produced against the target cell pulsed with the appropriate peptide, while IFN_7 is indicated against the target cell not pulsed with any peptide. Figure 3 consists of a series of line graphs (3) and (];)), which are shown by VANGL1-A02-9-1 94 (sequence identification number: 丨) (a) and VANGL1-A02 -9-484 (SEQ ID NO: 21) (b) Stimulated dilution of stimulated cytotoxic thymic lymphocyte cell lines IFN-γ production by cytotoxic lytic lymphocyte replication was established. The results showed that the cytotoxic T lymphocyte replication established by stimulation with each peptide showed strong IFN-7 production compared with the control group. In the figure, "indicating IFN-γ production against a target cell pulsed with a suitable peptide, and "indicating IFN-r production against a target cell not pulsed with any peptide. Figure 4 is a first-line diagram, Specific cytotoxic thymocyte activity against target cells of exogenous expression vANGU and hla-a* 0201 was displayed. COS7 cells transfected with HLA-A* 0201 or full-length VANGL1 gene were prepared as control group. A02-9-484 (SEQ ID NO: 21) established cytotoxic T lymphocyte cell line showing specific cytotoxic τ lymphocyte activity against COS7 cells transfected with both VANGL1 and HLA-A* 0201 104 201211250 Sex (black diamond). On the other hand, no significant specific cytotoxic T lymphocyte activity was detected, which was resistant to any target cell of HLA-A* 020 1 (triangle) or VANGL1 (circle). Main component symbol description] None 105 2012112 50 Sequence Listing &lt;110&gt; Tumor Therapy Science Co., Ltd. &lt;120&gt; VANGL1 peptide and vaccine containing the peptide <130> 0NC-A1030-TW &lt;150&gt; US 61/380,618 &lt;151&gt; 2010- 09-07 &lt;160&gt; 73 &lt;170&gt; Patent In version 3. 5 &lt;210> 1 &lt;211> 9 &lt;212&gt; PRT &lt;213&gt; Artificial sequence &lt;220&gt;&lt;223&gt; Peptide sequence <400> 1 Phe Leu Phe Val Val Ser Tyr Trp Leu 1 5 &lt;210〉 2 &lt;211&gt; 9 <212> PRT &lt;213> Artificial sequence &lt;220&gt;&lt;223> Synthetic peptide sequence <400> 2 Leu Leu Val Leu lie Phe Leu Phe Val 1 5 &lt;210> 3 &lt;211> 9 &lt;212> PRT &lt;213> Artificial sequence &lt;220> 201211250 <223> Manufactured peptide sequence &lt; 400> 3 lie Leu Leu lie Gly Thr Trp Ala Leu 1 5 &lt;210> 4 &lt;211> 9 &lt;212&gt; PRT <213>Artificial sequence &lt;220> <223> Synthetic peptide sequence &lt;400 〉 4

Ala Leu Leu Leu Val Leu lie Phe Leu <210> 5 &lt;211&gt; 9 &lt;212&gt; PRT &lt;213>Artificial sequence &lt;220> &lt;223>Synthetic peptide sequence &lt;400&gt;

Leu Val Leu lie Phe Leu Phe Val Val &lt;210&gt; 6 &lt;211&gt; 9 &lt;212&gt; PRT <213>Artificial sequence &lt;220> &lt;223>Synthetic peptide sequence &lt;400> 6

Ser Leu Val Asp Ala Leu Leu Phe lie 1 5 &lt;210〉 7 &lt;211&gt; 9 2 201211250

&lt;212&gt; PRT &lt;213>Artificial sequence <220> <223> Synthetic peptide sequence &lt;400&gt; 7

Phe Leu Gly Leu Leu Val Phe Leu Thr <210> 8 <211> 9 <212> PRT <213> Artificial Sequence &lt;220&gt;&lt;223> Synthetic peptide sequence &lt;400〉 8

Gly Leu Leu Val Phe Leu Thr Pro lie <210> 9 &lt;211&gt; 9 <212> PRT <213>Artificial sequence &lt;220> <223> Manufactured peptide sequence <400> 9

Gly Leu Arg Asp Gly lie Val Phe Val 1 5 &lt;210&gt; 10 &lt;211> 9 &lt;212> PRT &lt;213>Artificial sequence &lt;220> &lt;223>Synthetic peptide sequence &lt;400> 10

Phe Val Phe Arg Ala Leu Leu Leu Val 201211250 &lt;210> 11 &lt;211> 9 &lt;212&gt; PRT &lt;213>Artificial sequence &lt;220&gt;&lt;223>Synthetic peptide sequence &lt;400>11

Phe Leu Thr Pro Me Ala Phe lie Leu 1 5 &lt;210> 12 &lt;211&gt; 9 &lt;212> PRT &lt;213>Artificial sequence &lt;220> &lt;223>Synthetic peptide sequence &lt;400&gt;

Tyr Leu Ala lie Val Leu Leu Glu Leu <210> 13 &lt;211&gt; 9 &lt;212> PRT &lt;213>Artificial sequence &lt;220> &lt;223> Synthetic peptide sequence &lt;400&gt; 13

Lys Leu Leu lie Leu Leu lie Gly Thr 1 5 &lt;210> 14 &lt;211> 9 &lt;212> PRT &lt;213> Artificial sequence &lt;220> &lt;223> Synthetic peptide sequence 4 201211250 &lt;400&gt ; 14

Trp Leu Ser Thr Gin Trp Arg Leu Val 1 5 <210> 15 &lt;211&gt; 9 &lt;212> PRT <213>Artificial sequence &lt;220> <223> Synthetic peptide sequence &lt;400&gt; 15 lie Leu Gin His Leu Ala Phe Cys lie &lt;210&gt; 16 <211> 9 <212> PRT <213>Artificial sequence &lt;220&gt; <223> Synthetic peptide sequence &lt;400> 16

Leu Leu Phe lie His Tyr Leu Ala lie 1 5 &lt;210&gt; 17 &lt;211&gt; 9 &lt;212> PRT &lt;213>Artificial sequence &lt;220&gt;<223&gt; Synthetic peptide sequence &lt;400> 17

Trp Leu Phe Tyr Gly Val Arg lie Leu 1 5 <210> 18 <211> 9 <212> PRT <213> Artificial sequence 201211250 &lt;220> &lt;223> Synthetic peptide sequence &lt;400&gt; 18

Leu Gin Tyr Asp Lys Asp Arg Trp Leu 1 5 &lt;210> 19 &lt;211&gt; 9 &lt;212> PRT &lt;213> Artificial sequence &lt;220> &lt;223> Synthetic peptide sequence &lt;400> 19

Leu Leu Thr Ala Ser Lys Phe Arg Ala <210> 20 &lt;211&gt; 9 &lt;212> PRT &lt;213>Artificial sequence &lt;220> &lt;223>Synthetic peptide sequence &lt;400> 20

Leu Gin Pro Met Phe Thr Leu Gin Val 1 5 &lt;210> 21 &lt;211&gt; 9 &lt;212&gt; PRT &lt;213&gt; Artificial sequence &lt;220&gt;&lt;223&gt; Synthetic peptide sequence &lt;400&gt;

Lys Cys Leu Asp Phe Ser Leu Val Val 201211250 - &lt;210> 22 &lt;211&gt; 9 &lt;212&gt; PRT &lt;213>Artificial sequence &lt;220&gt;<223&gt; Synthetic peptide sequence &lt;400&gt;

Tyr Gin Gly lie Val Gin Tyr Ala Val 1 5 &lt;210&gt; 23 &lt;211> 9 &lt;212> PRT &lt;213&gt; Artificial sequence &lt;220&gt;&lt;223&gt; Synthetic peptide sequence &lt;400&gt;

Ser lie Leu Gin His Leu Ala Phe Cys 1 5 &lt;210&gt; 24 &lt;211&gt; 9 &lt;212> PRT &lt; 213 &gt; 213 &gt; artificial sequence &lt;220 &lt; 223 &gt; 223 &gt; synthetic peptide sequence &lt;400&gt;

Arg Val Phe Val Phe Arg Ala Leu Leu &lt;210> 25 &lt;211&gt; 9 &lt;212&gt; PRT <213>Artificial sequence &lt;220> &lt;223>Synthetic peptide sequence &lt;400&gt; 25 201211250

Phe lie Ser Met Ala Phe Lys Leu Leu 1 5 &lt;210&gt; 26 &lt;211&gt; 9 &lt;212&gt; PRT &lt;213&gt; Artificial sequence &lt;220&gt;&lt;223&gt; Synthetic peptide sequence &lt;400&gt;

Ser Leu Val Val Asn Val Lys Lys lie 1 5 <210> 27 <211> 9 <212> PRT &lt;213>Artificial Sequence&lt;220> &lt;223>Synthetic Peptide Sequence &lt;400〉 27 lie Val Gin Tyr Ala Val Ser Leu Val 1 5 <210> 28 <211> 9 &lt;212> PRT &lt;213>Artificial Sequence&lt;220> &lt;223>Synthetic peptide sequence&lt;400> 28 Leu 11 1 e Leu Leu lie Gly Thr Trp Ala 5 &lt;210> 29 &lt;211&gt; 9 &lt;212&gt; PRT <213> Artificial sequence 8 <220> 201211250 • &lt;223> Synthetic peptide sequence &lt;400> 29

Ala Leu Leu Phe lie His Tyr Leu Ala &lt;210&gt; 30 <211> 9 <212> PRT &lt;213>Artificial sequence &lt;220> &lt;223>Synthetic peptide sequence &lt;400&gt; 30

Phe lie lie Leu Ser Glu Glu Phe lie 1 5 &lt;210&gt; 31 &lt;211> 9 &lt;212> PRT &lt;213>Artificial sequence &lt;220> &lt;223>Synthetic peptide sequence &lt;400&gt;

Ser Met Ala Phe Lys Leu Leu Me Leu 1 5 &lt;210&gt; 32 &lt;211&gt; 9 <212> PRT &lt;213>Artificial sequence &lt;220> &lt;223>Synthetic peptide sequence &lt;400&gt; 32

Leu Leu Gly Asn Asp Ser Thr Arg Thr 1 5 <210> 33 &lt;211> 9 201211250 &lt;212&gt; PRT &lt;213>Artificial Sequence &lt;220> &lt;223>Synthetic Peptide Sequence &lt;400&gt; 33

Phe Val Leu Arg Leu Gin Ser Glu Thr 1 5 &lt;210> 34 &lt;211> 10 &lt;212> PRT &lt;213>Artificial sequence &lt;220&gt; <223> Manufactured peptide sequence &lt;400> 34

Leu Leu Leu Val Leu lie Phe Leu Phe Val 1 5 10 &lt;210&gt; 35 &lt;211> 10 <212> PRT &lt;213>Artificial Sequence &lt;220> &lt;223>Synthetic Peptide Sequence &lt;400〉 35

Leu Leu Val Leu Me Phe Leu Phe Val Val 1 5 10 <210> 36 &lt;211> 10 <212> PRT <213>Artificial sequence &lt;220> <223> Synthetic peptide sequence &lt;400> 36

Tyr Leu Gly Leu Thr Val Ala Ser Phe Leu 1 5 10 10 201211250 &lt;210> 37 &lt;211> 10 &lt;212> PRT &lt;213&gt; Artificial Sequence &lt;220> <223> Synthetic peptide sequence &lt; 400> 37

Gly Leu Phe lie Ser Met Ala Phe Lys Leu 1 5 10 <210> 38 &lt;211&gt; 10 <212> PRT &lt;213>Artificial sequence &lt;220&gt;<223&gt; Synthetic peptide sequence &lt;400> 38

Leu Leu Phe lie His Tyr Leu Ala lie Val 1 5 10 &lt;210> 39 &lt;211&gt; 10 <212> PRT <213> Artificial sequence &lt;220> &lt;223> Synthetic peptide sequence &lt;400> 39

Gin Leu Gin Pro Met Phe Thr Leu Gin Val 1 5 10 &lt;210&gt; 40 &lt;211&gt; 10 <212> PRT <213> Artificial Sequence &lt;220&gt;&lt;223> Synthetic peptide sequence 201211250 &lt;400&gt; 40

Phe Leu Thr Pro lie Ala Phe lie Leu Leu 1 5 10 <210> 41 &lt;211&gt;&lt;212&gt;&lt;213> 10 PRT artificial sequence <220> &lt;223> Synthetic peptide sequence <400> 41

Phe Val Leu Lys Cys Leu Asp Phe Ser Leu 1 5 10 &lt;210> &lt;211&gt;&lt;212>&lt;213> 42 10 PRT artificial sequence &lt;220&gt;&lt;223&gt; Synthetic peptide sequence <400> 42

Leu lie Leu Leu lie Gly Thr Trp Ala Leu 1 5 10 &lt;210> 43 &lt;211> &lt;212> &lt;213> 10 PRT artificial sequence &lt;220&gt;&lt;223&gt; Synthetic peptide sequence &lt;400 〉 43

Asn Leu Leu Thr Ala Ser Lys Phe Arg Ala 1 5 10 &lt;210> &lt;211&gt;<212&gt;&lt;213&gt; 44 10 PRT artificial sequence 12 201211250 <220> &lt;223> Synthetic peptide sequence &lt;400 〉 44

Phe lie Asp Pro Lys Ser His Lys Phe Val 1 5 10 &lt;210> 45 &lt;211> 10 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptide sequence &lt;400&gt; 45

Ser Met Ala Arg Ala Leu Gin Lys Tyr Leu 1 5 10 <210> 46 <211> 10 &lt;212&gt; PRT &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt;&gt;223 Synthetic peptide sequence&lt;400&gt; Lie Leu Trp Arg Asp Glu Leu Glu Pro Cys 15 10 &lt;210&gt; 47 &lt;211> 10 <212> PRT &lt;213>Artificial Sequence &lt;220> <223> Synthetic peptide sequence &lt;400> 47

Leu Val Phe Leu Thr Pro lie Ala Phe lie 1 5 10 13 201211250 <210> 48 <211> <212> <213> 10 PRT artificial sequence &lt;220〉 &lt;223&gt; Synthetic peptide sequence <400> 48

Cys Leu Asp Phe Ser Leu Val Val Asn Val 1 5 10 <210> 49 &lt;211&gt;&lt;212>&lt;213> 10 PRT artificial sequence &lt;220&gt;&lt;223> Synthetic peptide sequence &lt;400&gt; 49

Ala Leu Leu Phe lie His Tyr Leu Ala lie 1 5 10 &lt;210&gt;&lt;211>&lt;212><213&gt; 50 10 PRT artificial sequence &lt;220> <223> Synthetic peptide sequence &lt;400&gt; 50

Leu Leu lie Leu Leu Ile Gly Thr Trp Ala 1 5 10 &lt;210&gt; 51 &lt;211> &lt;212> &lt;213> 10 PRT artificial sequence <220> &lt;223&gt; Synthetic peptide sequence &lt;400&gt; 51 14 201211250 • Gly Leu Thr Val Ala Ser Phe Leu 61y Leu 1 5 10 &lt;210> 52 &lt;211> <212> &lt;213&gt; 10 PRT Artificial Sequence <220> &lt;223&gt; Synthetic peptide sequence &lt;223&gt;;400> 52

Gly Leu Arg Asp Gly lie Val Phe Val Leu 1 5 10 &lt;210&gt; 53 &lt;211&gt;<212&gt;&lt;213&gt; 10 PRT artificial sequence &lt;220> &lt;223> Synthetic peptide sequence &lt;400&gt; 53

Ser Met Ala Phe Lys Leu Leu lie Leu Leu 1 5 10 &lt;210> 54 &lt;211> <212> &lt;213&gt; 10 PRT artificial sequence &lt;220> &lt;223> Synthetic peptide sequence &lt;400&gt; 54

Phe I le His Tyr Leu Ala lie Val Leu Leu 1 5 10 &lt;210&gt; 55 <211> &lt;212> &lt;213> &lt;220> 10 PRT artificial sequence 15 201211250 &lt;223>synthetic peptide sequence &lt;223> ;400&gt; 55

Ser Ile Leu Gin His Leu Ala Phe Cys lie 1 5 10 &lt;210> 56 &lt;211> 10 <212> PRT <213> Artificial sequence <220> &lt;223> Synthetic peptide sequence &lt;400> 56 Phe Va! I Phe Arg Ala Leu Leu Leu Val Leu 1 5 10 &lt;210> 57 &lt;211> 10 <212> PRT &lt;213> Artificial sequence <220> <223> Synthetic peptide sequence &lt;400> 57 Phe lie Ser Met Ala Phe Lys Leu Leu lie 1 5 10 &lt;210&gt; 58 <211> 10 <212> PRT <213> Artificial sequence <220> <223> Synthetic peptide sequence <400> 58 Thr Leu Gin Tyr Asp Lys Asp Arg Trp Leu 1 5 10 &lt;210&gt; 59 <211> 10 16 201211250 • &lt;212&gt;&lt;213> PRT artificial sequence <220> <223> Synthetic peptide sequence &lt;400> 59

Gly Me Val Gin Tyr Ala Val Ser Leu Val 1 5 10 &lt;210&gt;&lt;211&gt;&lt;212&gt;&lt;213&gt; 60 10 PRT artificial sequence &lt;220&gt;&lt;223> Synthetic peptide sequence &lt;400 〉 60

Asn Gly Leu Arg Asp 6ly lie Val Phe Val 1 5 10 &lt;210&gt; 61 &lt;211&gt;&lt;212&gt;&lt;213> 10 PRT artificial sequence &lt;220&gt;&lt;223> Synthetic peptide sequence &lt;400&gt;; 61 -

Val Val Ser Tyr Trp Leu Phe Tyr Gly Val 1 5 10 &lt;210〉 &lt;211&gt;&lt;212&gt;&lt;213&gt; 62 10 PRT Artificial Sequence &lt;220&gt;&lt;223&gt; Synthetic peptide sequence &lt;400&gt;; 62

Val Val Asn Val Lys Lys lie Pro Phe lie 1 5 10 17 201211250 &lt;210&gt; 63 &lt;211> 10 &lt;212> PRT &lt;213> Artificial Sequence &lt;220> <223> Synthetic peptide sequence &lt; 400> 63

Phe Leu Phe Val Val Ser Tyr Trp Leu Phe 1 5 10 <210> 64 <211> 10 &lt;212> PRT &lt;213>Artificial sequence &lt;220&gt;<223&gt; Synthetic peptide sequence &lt;400&gt; 64

Asp Met Pro Arg Val Phe Val Phe Arg Ala 1 5 10 &lt;210> 65 <211> 10 &lt;212&gt; PRT &lt;213&gt; Artificial Sequence &lt;220> &lt;223> Synthetic peptide sequence &lt;400&gt; 65

Gly Leu Asp Cys Lys Arg Tyr Leu Gly Leu 1 &lt;210> 5 66 &lt;211> 10 &lt;212&gt; PRT &lt;213&gt; Artificial Sequence &lt;220&gt;&lt;223&gt; Synthetic peptide sequence 18 201211250 • 400> 66

Ser Leu Gly His Leu Ser lie Gin Arg Ala 1 5 10 &gt;&gt;&gt;&gt; 0 12 3 1— 1— 11 1— 2 2 2 2 67 10

PRT artificial sequence &lt;220> <223> artificial synthetic peptide sequence &lt;400&gt; 67

Leu Gin Pro Met Phe Thr Leu Gin Val Val 1 5 10 &lt;210&gt; 68 <211> 8691 &lt;212&gt; DNA <213> Human <400> 68 aggaagcgga aagcagcagt gcagcggcgg cggcggcggg gctctgcctc tccaggagcc 60 cagcgcaggc cgcagagccg gggccgctgt gagccgagac cgcgggccgc ggagctcggg 120 cggccggcgc ggagaatttg ttcctgttga agagtggctc ctcttctaat ttccagactc 180 cttgaggttt taggagtctg gtaggtgaaa ttttctacct ctaaggagaa acagtacctg 240 ctccttcctc aagcgcaagc cctccattgc tatggatacc gaatccactt attctggata 300 ttcttactat tcaagtcatt cgaaaaaatc tcacagacaa ggggaaagaa ctagagagag 360 acacaagtca ccccggaata aagacggcag agggtcagaa aagtctgtca ccattcaacc 420 tcccactgga gagcccctgt tgggaaatga ttctactcgg acagaggaag ttcaggatga 480 caactgggga gagaccacca cggccatcac aggcacctcg gagcacagca tatcccaaga 540 ggacattgcc aggatcagca Aggacatgga ggacagcgtg gggctggatt gcaaacgcta 600 cctgggcctc accgtcgcct cttttcttgg acttctagtt ttcctcaccc ctattgcctt 660 catcctttta cctccgatcc tgtggaggga tgagctggag ccttgtggca caatttgtga 720 ggggctcttt atctccatgg cattcaaact cctcat tctg ctcataggga cctgggcact 780 19 201211250 ttttttccgc aagcggagag ctgacatgcc ggtcctcatc tttctctttg tggtttccta ctctcgggac cggaattacc agggcattgt cctcttcatc cattacctgg ccatcgtcct cacgctgcag gtggtccgct ccaccgatgg gagtatccag cgagcagcat tggtggtcct taacccaaac ctcctaacag cctccaaatt agtctacaat gtagatggcc ccagtaacaa tgcagctgct cggcgcaggg actcaagcca tgaacggcga gtaaagaagc ggaaagcaag ccacattcag cgtctccagg ctgaggagca tagggaggcc gcccaggcca ttttcccctc catcacccgg cagcagaact accacagcat catcaccaac ggcatgaccc ccaaggcctt cctgcaatat gacaaggacc gctggctctc tgtgactaat ggattacggg atggaattgt cgtagtcaat gtgaagaaaa ttccattcat atctcacaaa tttgtccttc gcttacagtc tggctttatt aaaaaaaaaa gaaaaatata gtctttttta aaaattcttc ttcattgctg ctttgaccat ctgcacttta tttggaagga actgatgaca tctgactttt gtcgatggga gttacagctg taaaccaaag tggagctggt tcctgccttt cgtccagtac caagtccccc ccaggggaca catctttatt ctgtttcagg ttgtgtatgt taatgtccag tatcacatca acgggtgttt gtgtttcgtg cccttttgtt 840 ttggcttttt tacggggtcc gcattttgga 900 gcaatatgca gtctcccttg tg gatgccct 960 gctggagctc aggcagctgc agcccatgtt 1020 cgagtcccgc ttctacagcc tgggacacct 1080 agaaaattac tacaaagatt tcaccatcta 1140 ccgagcagcc aagcatatgg ccgggctgaa 1200 tgccactggc cagtcccggg ccatgattgc 1260 caacgagttg tattatgaag aggccgaaca 1320 gctggtggtt gcagtggaag aggccttcat 1380 gcagaaagcc ccaggggagg tgatggaccc 1440 catggccagg gctctccaga agtacctgcg 1500 ggagagcatc ctgcagcacc tggccttctg 1560 cctagaacgg tacctcagtg cgggccccac 1620 tacacagtgg aggcttgtca gtgatgaggc 1680 gttcgtcctt aagtgcttgg acttcagcct 1740 catactctct gaagagttca tagaccccaa 1800 tgagacatcc gtttaaaagt tctatatttg 1860 tagagagata tatatctatg ccagaggggt 1920 actgaaactg gcagatgatt gaccagtatc 1980 agcaggggct gtccaccctg aaaaagagtg 2040 cttctcaaga agccattcct tggagcttct 2100 gcttcttggg agcctcgcct tacaactaat 2160 gttgcttctg gtcagcccac ttgtagactt 2220 aaaccagtca cgacacgtcc acatatgtat 2280 cccatgaaag tcgtgggcag ttcaggagat 2340 20 201211250, acctgccttc atctttgttc tttgttgcct Aatgtacact gtcgtttaca gctattaagt aacctacctg ccctgtttct gatcccac cc ccagccctgc agctgcccac ctggcctcca ctggctctcc atgtgtgccc tccggctctg ttccataggg aagtgtgggg tgcccagcag tgccaccttt aggctgcagc aggagcccca caccaaccag gggagactaa cactgtgact ttaatttcct ggggacgtaa gttcttccca accaaaccat gccaaccacg ctggcaactg ccgtcactgt gcaactcatc gcctctgcca cccactctta gttgctgata aagtggggag gaagggagag tagggagccc atcttgtcca cacagctgat ttcagtgggc tttcccctgg gggcagagga gccatcctgg cggagccctg cggacctctt gcactgggct gcctttgcct ttttaaaagt gttcactctt gctttttcca tacaggatga cattgtcgaa tgctctttgt cttcatacac tccacaagtg gtacagtatt tggatctttg taatacacct gtacctgaaa tcagcttgaa aagacatgct ggagaagaag ccaagatgta ctattcaact atgtgtttct ggtgcttttg ttcttagttt ttgccgttag tctttctcag gaaatatttt gggaaatggg gtcagaggtt gctacgtcat ggatacagtg atagttaata atgacactgt tcatcaccat taggttcttc agagaaagat cacaacaaaa 2400 gatttgattt tgtttttttc ccaaagagaa 2460 ctctgctggc ttgaagcagg taaccctttc 2520 tgccatcctg cccccacctg gctggcagcc 2580 tgtgaagcct caagtcagtc ccagcattgt 2640 gtaaagcaca gggagagagg gcagtgggaa 2700 cactgcccag ttttcctccc cactgttcta 2760 ctgggattgg caggtgcaac ttggagccac 2820 agcttagagc aagctgccct gccaaaggag 2880 ctgctgtcca gtccctgtgt tttctgacca 2940 cttaggacca ggaaagaggc tggttttgct 3000 aaggaaaatg gacactctac agagtttggg 3060 gaaagattca tctgtggtct gtctgttaaa 3120 ccctggggga gcagacactg actgggttgt 3180 ctgcagggga gctccttcag gagccccatc 3240 ccatttgcct tcctgtatct gcaacaaacc 3300 gtatttcggt aatcagccat cttgctgtag 3360 atgtgtgcac acccccttac tcccttactg 3420 ttgtgtcatt gtaaaaatca aaattggctt 3480 aagtaaacaa cattcttcaa ttactagcct 3540 gaagggggaa cccataggtg tggcgtggag 3600 gtttataaaa aacacatacc atggaaccat 3660 atcccttcaa actggaagtt ccttacaata 3720 gtaagagatg gcaagtgtga gacgggctgt 3780 cagttccaag tgccataagt gtatgtacat 3840 tctaaaatac tgttcttcca accctatctt 3900 21 201211250 caatgaccag tccagaaggg gttaagctgg cagggtgaag aaaggtttaa attaaagaat ccagtctttg cataggagaa tgttagacat gtattgattt ttttatattg actttgtatt atgcaggatc tttgtaaagc ctttgcactt cagtgggaac aatgtaaatg acatttaaaa aattgaacac Aatgcatttt tatttcaatt gggg&a mp; taaac ttcgccctaa ggctggtaga tcatttgcct tatatgttta tagatttttt agcattgagt gttaaagaac ttaatgagga tgatgtttta actggtagat aatttgttct tttatagtcc atgaactgaa tgttaaaaag agctatatag ttcatccatc ctttgcatta tggctaaaat tcataaagta agccctagag ctatcatcac ctcccttccc ccgcctctgt agttctttac agcaaatggt aagaggcagg attgcctggg gcttgggact ccttttttaa gatagggata aagtgctcac ccctgccctc cattttgcct cataatcact ttcgagtgca gatgctacca gcatattgga ctgacagaaa tgagtgagtg ctccagccac tcagtgaaac aatctgggtc ctgctgtgta agtatcccta tatttccata tatgtgagca tttctctgag gtcagacatc ttaacatctg tgttatctgt attgtgtata tagctgagtg tgtgagggtg agatgactta ataaccctgt gttttgagag attcatttgc tctggcatgt gcattcccag 3960 ttattttctc tctccccctt cctctttctc 4020 tcagaaatta ctgtttctgt tttaaattga 4080 .gagttctttt tgaaagaata acaaaataaa 4140 tcaacctctt tatagcttga gttacttttg 4200 gatttaaggt ttcagaaagc tgcatcccac 4260 cttggaactg gtaggctatt ctttttaaaa 4320 atgtatgttc acattatagt agacaggatt 4380 ataattttca tcctacgtta ttaaaattag 4440 gtctatatct gagattgctc tcttccctgg 4500 taaatatgta cttttgaaga taggacagtt 4560 ttctgtatgc attctcagag aggattttaa 4620 tcaaaatgtt aagtcaaatc tgtaatactt 4680 aaaatacttg accaccaaat ttttgcccaa 4740 tcttgccttt tgacatctac atggaagaca 4800 tgacctggtg tgtttgctgt gttgtagttc 4860 tggagagact agctgtgcag gtgtgtgttg 4920 tctacagtag ttggtggtag atttctctct 4980 tgtatttacc taagggctgt agctctgtgg 5040 ttgattacct tgccactcca acctacgtac 5100 caacaaaagt gagtccttgg tttaccttcc 5160 agtggggatg catatttgtt tgtgcgtttt 5220 tgtattacca gacggatagc acatttatat 5280 agcaggtgtg tagctcagca gatacgtgtc 5340 tctgtgtttc tgcagtcccc tgtgtttgag 5400 gtcgctctaa accagtgact tttccctccc 5460 22 201211250 &quot; ctgctttatt cctttccctc actgacactg acagcactgt cttctgggga gcctgctgtc ctttaggact ctgaaaacag caagaaacaa ctgctcaaac ttcactaccc tggaagcctt tgggctttat ttttaaaaag tgataggtta agagaccctg tatttaaata gtcctgcagc cagtgcagta ataactgcat tgagctttaa tagtgtttgt gatttacgga tttgttactg ctactatgta accttgtggt cgtatttcat caccgttctt gattggtatt ccaagtgtat tgacaaaaca Tgttttggtc aaagaaagga atg tcacagt ccgtgttcca cccagccttg atcttggttt ttcgggtgaa aaacggaagg atgtctggtt aacagaattt caaactagat cttgaagtat ggtctaaatg attcggcact atccttgaac tagaacctgg ggtgagagtt tggatttaca ccttgtccct tggaaagctt tttgatggaa agaacttgag aatcccttct gctgcaagac agggatgctg ttgttctggc ttctgctccc actctgctgg cttgggcaag gcaggcaggg gcttgacctg gcctctctct cttccctggt tggagtgaga ggggctgtcc gagtccctgg cctggcctcc ttgacgtagg tctttctcac acttgccccc aagacttttg accatttttc tctgttccca tatgtagtaa tttctgccct gctgtttgct ttcaatggaa gcttctcccg ctagagtaaa tggctttagc 5520 ctgcaggcaa gtccattaaa ctctttcttg 5580 acaaacaaag gtcaagctct aagaaaatta 5640 actagatatt tcttaaggta acttaaaaat 5700 cttacagtag cacagaaatg ttagcatatt 5760 cgattgtaaa gtgatttaag tatttctggg 5820 aaaaacaaaa aaatcactac tgtgaattta 5880 tataaataaa ataagaattg ctcttctgcc 5940 gcgaaatgag atagtttaga cactgttgaa 6000 gctcagaaaa ttcagttttg gatcacattt 6060 aaggctacta acacatttat caggtaatgt 6120 ttatccccac attctttcaa gataggagtc 6180 tcagagagga aggggcttgt ccaaggtctc 6240 gtttgattct aac ccctcag tccactgtac 6300 tctggatgtt gaggaaggac ctagagacac 6360 cattgggagg caggatctct tctttcactt 6420 ctccactatg ctagcaaata tcttaggata 6480 ggaaaaccca gcctttcagt gttaacacct 6540 agcccccctt tgcttttgcc tggccccacc 6600 atgcgtgcct tgggccttgg gtgcagggag 6660 ggtgccatgg caacattatg ccccaaactt 6720 acagccccat cctgtgggga tctcaagccg 6780 tgttctcagc aagcagtttg catcccaccg 6840 acagagcaga cgtaaaacag gactcagaaa 6900 gttttgattc agttgtgcat aaaccatagt 6960 gacagtaaag ggaagatggt gctcacatct 7020 23 201211250 ctccatgtga catctcatta ggaattaaga ataaaattaa atttcagggc tctataagtc gtagataacc caatttgttt tgtctatgaa ctccaacaaa agagcagatt cctaaagcca atggcaccaa gactctacca tttatgtctc ttgtcatagt ggaagaaaga cacttacttt ggcttttatc ttaaaagtgt ctttggcact cattatttga atgtacagtt gtttggtttt ttgtagacat ggccttttgt tgtgaagttg agccttcagc ctaagaaagc ttcatctgtg gtgatgggac ttgggcatct gatctgcagg gaatttagac agttgcacat cattgccgtt gtttttcatt taccagcacc tctcagttat tcatcattct ttaaaaaggg aacatacaaa taatagttta cggtaggctt taattaaatg cgtgattagc c aaatttgat ttccaacagt caggatgcca gcaaagatga gggtgggggc atagatgacc ccttcctcaa cagaaatgct caggtcttat ttgagaggag attatttgat cctgatttca agtccagcac caatttagaa tgacagagtc ataacggttt gtgtaaaaat ttagttaata ctgtacattg taaccaggag ggtcaccata tgtgtatgac aaggcctgag cttttgacac atttgcaagc atgtaaatga aggtccattt acttacattc ataaggttta agtaacagag ttagtgtctc tgatggaata tgcgatggat tagaaatgta aaacttcaga 7080 ccgttttccc aggtcctgtt ccgtttctac 7140 ataagcctct ttagtgggtt gttttagtct 7200 ggtgcagcac tgtgaaaagt ttctttcaat 7260 tctcagctta caaacatcag cgttttgtcc 7320 aagctttggg gacaaaggtg acaaacccca 7380 tcttttggca ctgaaatggt atttgggaag 7440 gtatgtgctt atctttatct gagctttcac 7500 ctcatcattt aggagtgttt aattctaaaa 7560 gggaccagag acttgttgct cagggagtta 7620 tgacaagttt agttcaactg aagttgtagg 7680 ctaggggcct tgtagaaaga tgaaacagtt 7740 agaggtaatg gaacattcgc ttacttttca 7800 aatctaaact atggcaataa tttattttta 7860 gcaaactcct ctgggacccc taagttatgg 7920 catttatggc cataactatt gcatagagtg 7980 agatactggc tcagtgattt aactcacatt 8040 Act gagagaa ccagagaggc ctgggccagg 8100 aattgctttg gttagaagga ctttacattt 8160 agttcagaga tgaaaccacc tgtctttacc 8220 gtggtcaggg accttttttg ttctttctga 8280 gggcagtttt gccaaccagc ctctgctcat 8340 tgagttcctg cataaactgg gtagtgggct 8400 atgaatgaca ctaccagcaa ccatctgtac 8460 tgctatgaaa cttcttctca ttgtgatgtc 8520 gtgtacctgt cacccaagtt attttgttcc 8580 24 201211250 8640 8691 tttttgggtc ctccagtata atccccccct catcccaatt aactgtaaaa tgttttacac atcacatttt ttatactgta aacttggaaa ataaactgaa Atatcaaatt g &lt;210&gt; 69 &lt;211> 524 &lt;212> PRT <213>human &lt;400&gt; 69

Met Asp Thr Glu Ser Thr Tyr Ser Gly Tyr Ser Tyr Tyr Ser Ser His 15 10 15

Ser Lys Lys Ser His Arg Gin Gly Glu Arg Thr Arg Glu Arg His Lys 20 25 30

Ser Pro Arg Asn Lys Asp Gly Arg Gly Ser Glu Lys Ser Val Thr lie 35 40 45

Gin Pro Pro Thr Gly Glu Pro Leu Leu Gly Asn Asp Ser Thr Arg Thr 50 55 60

Glu Glu Val Gin Asp Asp Asn Trp Gly Glu Thr Thr Thr Ala lie Thr 65 70 75 80

Gly Thr Ser Glu His Ser lie Ser Gin Glu Asp lie Ala Arg lie Ser 85 90 95

Lys Asp Met Glu Asp Ser Val Gly Leu Asp Cys Lys Arg Tyr Leu Gly 100 105 110

Leu Thr Val Ala Ser Phe Leu Gly Leu Leu Val Phe Leu Thr Pro lie 115 120 125

Ala Phe Ile Leu Leu Pro Pro Ile Leu Trp Arg Asp Glu Leu Glu Pro 130 135 140

Cys Gly Thr lie Cys Glu Gly Leu Phe lie Ser Met Ala Phe Lys Leu 145 150 155 160 25 201211250

Leu lie Leu Leu lie Gly Thr Trp Ala Leu Phe Phe Arg Lys Arg Arg 165 170 175

Ala Asp Met Pro Arg Val Phe Val Phe Arg Ala Leu Leu Leu Val Leu 180 185 190 lie Phe Leu Phe Val Val Ser Tyr Trp Leu Phe Tyr Gly Val Arg lie 195 200 205

Leu Asp Ser Arg Asp Arg Asn Tyr Gin Gly lie Val Gin Tyr Ala Val 210 215 220

Ser Leu Val Asp Ala Leu Leu Phe lie His Tyr Leu Ala lie Val Leu 225 230 235 240

Leu Glu Leu Arg Gin Leu Gin Pro Met Phe Thr Leu Gin Val Val Arg 245 250 255

Ser Thr Asp Gly Glu Ser Arg Phe Tyr Ser Leu Gly His Leu Ser lie 260 265 270

Gin Arg Ala Ala Leu Val Val Leu Glu Asn Tyr Tyr Lys Asp Phe Thr 275 280 285 lie Tyr Asn Pro Asn Leu Leu Thr Ala Ser Lys Phe Arg Ala Ala Lys 290 295 300

His Met Ala Gly Leu Lys Val Tyr Asn Val Asp Gly Pro Ser Asn Asn 305 310 315 320

Ala Thr Gly Gin Ser Arg Ala Met lie Ala Ala Ala Ala Arg Arg Arg 325 330 335

Asp Ser Ser His Asn Glu Leu Tyr Tyr Glu Glu Ala Glu His Glu Arg 340 345 350

Arg Val Lys Lys Arg Lys Ala Arg Leu Val Val Ala Val Glu Glu Ala 355 360 365 26 201211250 * Phe lie His lie Gin Arg Leu Gin Ala Glu Glu 6ln Gin Lys Ala Pro 370 375 380

Gly Glu Val Met Asp Pro Arg Glu Ala Ala Gin Ala lie Phe Pro Ser 385 390 395 400

Met Ala Arg Ala Leu Gin Lys Tyr Leu Arg Ile Thr Arg Gin Gin Asn 405 410 415

Tyr His Ser Met Glu Ser lie Leu Gin His Leu Ala Phe Cys lie Thr 420 425 430

Asn Gly Met Thr Pro Lys Ala Phe Leu Glu Arg Tyr Leu Ser Ala Gly 435 440 445

Pro Thr Leu Gin Tyr Asp Lys Asp Arg Trp Leu Ser Thr Gin Trp Arg 450 455 460

Leu Val Ser Asp Glu Ala Val Thr Asn Gly Leu Arg Asp Gly lie Val 465 470 475 480

Phe Val Leu Lys Cys Leu Asp Phe Ser Leu Val Val Asn Val Lys Lys 485 490 495

Me Pro Phe lie I le Leu Ser Glu Glu Phe Me Asp Pro Lys Ser His 500 505 510

Lys Phe Val Leu Arg Leu Gin Ser Glu Thr Ser Val 515 520 <210> 70 &lt;211> 22 &lt;212&gt; DNA <213>Artificial Sequence&lt;220> <223> Manual Sequence&lt;400> 70 gtctaccagg cattcgcttc at 22 27 201211250 <210> 71 &lt;211> <212> &lt;213> 24 DNA artificial sequence <220> <223> Artificial sequence &lt;400> 71 tcagctggac cacagccgca gcgt 24 &lt;210&gt; 72 &lt;211> &lt; 212> <213> 21 DNA artificial sequence &lt;220&gt;&lt;223&gt; Artificial sequence &lt;400&gt; 72 tcagaaatcc tttctcttga c 21 &lt;210&gt; 73 &lt;211> &lt;212&gt;&lt;213> 24 DNA artificial sequence &lt;213> ;220> &lt;223&gt; Manual Sequence &lt;400&gt; 73 ctagcctctg gaatcctttc tctt 24 28

Claims (1)

201211250 VII. Patent application scope: 1. An isolated peptide having the cytotoxic thymocyte stimulating ability, wherein the peptide is composed of an amino acid sequence of VANGL1 or an immunologically active fragment thereof. 2. The isolated peptide according to claim 1, wherein the peptide comprises an amino acid sequence, and the group consisting of free sequence identification numbers: 1, 12 and 21. 3. An isolated peptide comprising an amino acid sequence in which 1, 2 or a plurality of amino acids are substituted, deleted, inserted and/or added to a free sequence identification number: 1, 1 2 and 21 The amino acid sequence of the group formed, and wherein the peptide has a cytotoxic T lymphocyte evoking ability. The isolated peptide of any one of claims 1 to 3 wherein the peptide binds to a human leukocyte antigen. 5. The isolated peptide according to claim 4, wherein the human white jk tissue antigen is human leukocyte antigen _ a 2 . 6. The peptide according to claim 5, wherein the peptide has one or both of the following characteristics: (a) an amine selected from the group consisting of a free sequence identification number &quot;, 12 and 21. The second amino acid at the N-terminus of the acid sequence (4) is a group consisting of leucine and methionine; and the group consisting of 12 and 21 is composed of lysine and leucine ( b) Select the free sequence identification number: i, the C-terminal amino acid of the amino acid sequence is selected from the group. 7. The peptide of the isolated 201211250 as described in any one of claims 6 to 6, wherein the peptide is a nine-peptide or a ten-win. 8 . An isolated multi-nucleotide acid, the total of which is the isolated peptide of any one of claims 1 to 7. 9. A composition for inducing a cytotoxic T lymphocyte, wherein the composition comprises one or more of the peptides as described in any one of the claims of the patent, No. A plurality of the polynucleic acid as described in claim 8 of the patent application. 10. A pharmaceutical composition for the treatment and/or prevention of cancer, and/or its avoidance of recurrence after surgery, wherein the composition comprises - or a plurality of items as claimed in claims 1 to 7 The peptide, or one or more of the polynucleic acid as described in claim 8 of the patent application. 11. The pharmaceutical composition of claim 1, wherein the composition is formulated for administration to a human body whose human leukocyte tissue antigen is human leukocyte antigen-A2. 12. A method of inducing an antigen-presenting cell having a cytotoxic T lymphocyte-inducing ability, comprising the steps of: grouping the following groups: (a) or licking an antigen to present cells as in claim 1 a peptide contact according to any one of the items 7 to 7 and (b) introducing a polynucleotide encoding the peptide according to any one of claims 1 to 7 into an antigen-presenting cell . 13. A method for inducing cytotoxic T lymphocytes, comprising the steps of: selecting a group consisting of: (a) co-culturing CD8-positive T cells with antigen-presenting cells, antigen 201211250 exhibiting cell expression of a human leukocyte The complex of the tissue antigen and the peptide as described in any one of claims 1 to 7 on the surface; (b) co-cultivation of the CD8-positive tau cells with the exogenous corpuscle a human leukocyte tissue antigen on a surface complex with a peptide as described in any one of claims 1-6, and (c) a nucleic acid encoding a tau cell receptor subunit The gene of the polynucleoside glucoside is introduced into a sputum cell, and the sputum cell receptor subunit multi-peptide is combined with the peptide as described in any one of claims 7 to 7. An isolated antigen-presenting cell which exhibits a complex of a human leukocyte antigen and a peptide as described in any one of the above-mentioned claims S1 to 7 on its surface. The antigen-presenting cell as described in claim 14 of the patent application is induced by the method as described in the scope of claim 12 of the patent application. 16&gt; An isolated cytotoxic sputum lymphocyte, which is characterized by a peptide as described in any one of claims 1 to 7 jg + &amp; x ^. The cytotoxic τ lymphocytes as described in claim 16 of the patent scope are induced by the method described in φ, Patent (4) (4). And a method for inducing an immune response to induce a primary cancer in an individual, comprising the step of administering a composition of the individual to the individual, the composition comprising any one of claims 1 to 7 of the patent application The peptide, one of its immunologically active 1 Η # 1, is also 'or encodes the peptide or one of the polynucleotides of the fragment. A plurality of or an immunologically active fragment thereof which is resistant to the peptide as described in any one of claims 1 to 7. 201211250 20. Any of the items 21. A scorpion vector comprising a nucleotide sequence encoding a peptide as described in claims 1 to 7 of the patent application. / Host cell, which is transformed or transfected with an expression vector as described in claim 20 of the patent application. A diagnostic kit comprising the peptide according to any one of claims 1 to 7 of the invention, as claimed in claim 8 or as described in claim 19 Antibody. 23. The isolated peptide according to any one of claims 1 to 7 of the patent application, which is selected from the group consisting of: 1, 2 and 21.