KR102335916B1 - Human leukocyte antigen A02:01 allele specific binding peptides and uses thereof - Google Patents

Abstract

A peptide that specifically binds to the human leucocyte antigen (HLA) A02:01 allele of cancer cells, a vaccine composition comprising the peptide as an active ingredient, a preventive or therapeutic agent for cancer, and a composition for diagnosis of cancer will be. Since the peptide specifically binding to the human leucocyte antigen (HLA) A02:01 allele of cancer cells according to an aspect has high immunogenicity, if it is utilized, cancer tissue expressing the A02:01 allele HLA It can induce a cellular immune response against Therefore, the peptide according to one aspect may ultimately be utilized as a therapeutic agent capable of preventing or treating cancer. In addition, the peptide according to an aspect is capable of specifically binding to cancer cells, thereby enabling diagnosis of cancer.

Description

Human leukocyte antigen A02:01 allele specific binding peptides and uses thereof

A peptide that specifically binds to the human leucocyte antigen (HLA) A02:01 allele of cancer cells, a vaccine composition comprising the peptide as an active ingredient, a preventive or therapeutic agent for cancer, and a composition for diagnosis of cancer will be.

Compared to normal cells, cancer is characterized by uncontrolled cell growth, ability to invade adjacent tissues, and sometimes metastasis. Cancer is basically a disease related to tissue growth regulation. When normal cells are transformed into cancer cells, the expression of genes that control cell growth and division is changed (Croce., The New England Journal of Medicine, 358). (5): 502-511, 2008).

Anticancer treatment includes oncogenes, anti-apoptotic molecules, telomerase, growth factor receptor genes ( It is performed by inhibiting the expression of genes necessary for the survival of cancer cells, such as growth factor receptor gene) and signaling molecules, or inducing apoptosis (Knudson AG, Nature reviews. Cancer 1(2): 157-162, 2001). However, there is a problem that not only cancer cells but also normal cells may be affected in such a treatment process, resulting in side effects.

Accordingly, there is a need for a cancer treatment vaccine as an alternative method for treating cancer. Cancer treatment vaccination is different from traditional vaccination to prevent infectious agents. In particular, cancer vaccines must induce an immune response against self-antigens rather than non-self-antigens. In addition, the vaccine should act when administered after cancer has formed, exhibit an immunosuppressive effect, and should not be sensitive to heterologous cancer antigen expression between patients.

Since many cancer antigens are autoantigens and immune tolerants, it is difficult to induce a specific immune response, and in particular, it is not easy to find antigens that can act in common in many cancers. However, if an antigenic peptide that induces a specific immune response to cancer cells is used, it may be usefully used for immunotherapy to specifically remove cancer cells expressing the antigen, but nothing has been known about this until now.

One aspect provides a peptide that specifically binds to the human leucocyte antigen (HLA) A02:01 allele of cancer cells.

One aspect provides a vaccine composition comprising the peptide as an active ingredient.

Another aspect provides a preventive or therapeutic agent for cancer comprising the peptide as an active ingredient.

Another aspect provides a composition for diagnosis of cancer comprising the peptide as an active ingredient.

In order to achieve the above object, there is provided a peptide that specifically binds to the human leucocyte antigen (HLA) A02:01 allele of cancer cells.

It provides a vaccine composition comprising the peptide as an active ingredient.

It provides a preventive or therapeutic agent for cancer comprising the peptide as an active ingredient.

It provides a composition for diagnosis of cancer comprising the peptide as an active ingredient.

A peptide that specifically binds to the human leucocyte antigen (HLA) A02:01 allele of cancer cells according to an aspect has high immunogenicity, so if it is utilized, cancer expressing the HLA-A02:01 allele It can induce a cellular immune response to tissues, so it can be used as a vaccine for cancer treatment. Therefore, the peptide according to one aspect may ultimately be utilized as a therapeutic agent capable of preventing or treating cancer. In addition, the peptide according to an aspect is capable of specifically binding to cancer cells, thereby enabling diagnosis of cancer.

1 is a diagram schematically schematically illustrating a method for obtaining a peptide having a high affinity for a human leukocyte antigen (HLA) commonly expressed from cancer tissues of a cancer patient.

One aspect provides a peptide that specifically binds to the human leucocyte antigen (HLA) A02:01 allele of cancer cells.

The term “human leukocyte antigen (HLA) is a gene complex encoding a human major histocompatibility complex (MHC) protein, and refers to a chromosomal region containing a gene that controls histocompatibility antigen. It is called human leukocyte antigen (HLA) and is abbreviated as the MHC complex. The term HLA used in the present specification has the same meaning as the major histocompatibility complex, and MHC and HLA may be used interchangeably in the present specification.

As used herein, the term "cancer" refers to or describes a physiological condition characterized by uncontrolled cell growth in mammals, which rapidly grows while infiltrating surrounding tissues and spreads or metastasizes to various parts of the body. It may include, without limitation, life-threatening malignancies. Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma and leukemia or lymphoid malignancy. More specific examples of these cancers include carcinomas derived from epithelial cells such as lung cancer, laryngeal cancer, stomach cancer, colorectal/rectal cancer, liver cancer, gallbladder cancer, pancreatic cancer, breast cancer, ovarian cancer, uterine cancer, cervical cancer, prostate cancer, kidney cancer, skin cancer, etc. ), bone cancer, muscle cancer, fat cancer, sarcoma derived from connective tissue cells such as fibroblast cancer, hematopoietic cancer derived from hematopoietic cells such as leukemia, lymphoma, multiple myeloma, tumors occurring in nerve tissue, and There are triple negative breast cancer as well as head and neck cancer.

The peptide according to an aspect may be one or more selected from the group consisting of a tumor-associated antigen (TAA) or a tumor specific antigen (TSA) and a neoantigen. The growth of cancer cells is known to occur when there is a defect in the immune system that identifies and removes them as non-self. The TAA is an antigen mainly found in some normal cells or cancer cells, and TSA is found in cancer cells. It is known that the antigen is not found in normal cells. Neoantigens are known to appear as a result of DNA mutation by carcinogens or as a result of expression of genetic material by oncogenic DNA viruses or RNA viruses. The peptide according to one aspect is present on the surface of cancer cells and binds to HLA, which helps immune cells to remove cancer cells, thereby inducing the immune system response to cancer cells, that is, immunologic surveillance to eliminate cancer cells. can

In one aspect, a peptide that specifically binds to the A02:01 allele among HLA class 1 most commonly expressed in triple-negative breast cancer patients was identified.

The peptide according to one aspect may consist of 5 to 50 amino acids, for example, may include 8 to 15 amino acids.

The peptide according to an aspect may consist of the amino acid sequence shown in SEQ ID NOs: 1 to 20, but any peptide capable of increasing the immunogenicity of T cells while specifically binding to A02:01 of cancer cells may be included without limitation.

The peptide according to an aspect may have an affinity for HLA of 500 nM or less, and the peptide may exhibit T cell-specific immunogenicity.

In an embodiment of one aspect, 20 types of peptides specifically binding to the A02:01 allele in HLA class 1 were identified, and specific 20 types of peptides are as follows.

SEQ ID NO: amino acid sequence length gene protein Affinity (IC50, nM) Immunogenicity score
Maximum TPM in normal tissue One KLYDGFQYL 9 PI4KB Phosphatidylinositol 4-kinase beta 3 0.064
98.27 2 KLVELPYTV 9 OSGEP Probable tRNA N6-adenosine threonylcarbamoyltransferase 4 0.112
80.51 3 ALQEKLWNV 9 INTS4 Integrator complex subunit 4 5 0.026
19.58 4 SLLDPVPEV 9 GCN1L1 Translational activator GCN1 5 0.096
72.52 5 TLADLVHHV 9 TRRAP Transformation/transcription domain-associated protein 5 0.109
27.77 6 FLANIGTSV 9 APPL1 DCC-interacting protein 13-alpha 5 0.104
40.54 7 NMVDIIHSV 9 PCCB Propionyl-CoA carboxylase beta chain, mitochondrial 5 0.221
41.90 8 LMVDHVTEV 9 SRA1 Steroid receptor RNA activator 1 5 0.197 69.56 9 NMLPQIFRV 9 C12orf4 Protein C12orf4 5 0.127 18.80 10 KLIGQVHEV 9 FRY Protein furry homolog 5 0.089 46.97 11 MITDVVPEV 9 TOX4 TOX high mobility group box family member 4 6 0.163 53.02 12 ALIEKLVEL 9 POLA2 DNA polymerase alpha subunit B 6 0.017 33.79 13 GQIEVVPEV 9 PHF3 PHD finger protein 3 7 0.272 43.11 14 SLSAFTPAL 9 MCM3AP Germinal-center associated nuclear protein 7 0.150 52.25 15 ILWETVPSM 9 FNDC3B Fibronectin type III domain-containing protein 3B 7 0.143 59.83 16 YITERIAV 9 TNS3 Tensin-3 8 0.424 92.87 17 ALLGILQHV 9 NUDCD3 NudC domain-containing protein 3 8 0.071 58.92 18 ALANGIEEV 9 APOL3 Apolipoprotein L3 8 0.307 67.69 19 GMAERIPEL 9 ACSL3 Long-chain-fatty-acid--CoA ligase 3 9 0.338 55.40 20 YLNQHIEHV 9 ERCC5 DNA repair protein complementing XP-G cells 9 0.142 36.63

In an embodiment of one aspect, the cancer tissue is crushed, dissolved with a lysate, and the HLA-antibody-resin expressed in the cancer tissue and the immunoprecipitation reaction (Immunoprecipitation) through the peptidome binding thereto and tC18 resin are purified by mass spectrometry was analyzed with From the mass spectrometry data, the primary cancer-associated antigenic peptide was identified by setting the enzyme specificity to unspecific, the false discovery rate to 0.01, the peptide length to 8 to 15, the maximum peptide mass to 1,500, and the maximum charge to be 3. sympathized.

In a later embodiment, the affinity for each HLA allele is analyzed using the NetMHC (https://www.cbs.dtu.dk/services/NetMHC/) program, and the IEDB Analysis Resource (https:// tools.iedb.org/immunogenicity/) program to analyze the immunogenicity of the primary cancer-associated antigen peptide, and finally, a total of 20 cancer-associated antigens with _{an affinity (IC 50 ) to HLA-A02:01 of 500 nM or less} The peptides of the species were selected.

One aspect provides a vaccine composition comprising the peptide as an active ingredient.

The vaccine composition may additionally include a buffering agent, isotonic agent, preservative, stabilizing agent and solubilizing agent. As the buffer, for example, phosphate, acetate, ammonium phosphate, ammonium carbonate, citrate and the like can be used. In addition, the vaccine composition may further include an adjuvant and an immunoactive material.

The vaccine can induce an antigen-specific humoral immune response as well as a high cellular immune response.

Since the vaccine contains the peptide as an active ingredient, a peptide that exists on the surface of cancer cells and helps immune cells to remove cancer cells binds to HLA and the response of the immune system to cancer cells, that is, immunologic surveillance (immunologic surveillance). ), so it can be used as a vaccine that can effectively prevent cancer. Therefore, the peptide specifically binds to HLA-A02:01, which is commonly expressed in cancer cells, and has high immunogenicity of T cells, so it can induce an immune response of immune cells. Since there is no sensitivity to heterologous cancer antigen expression between patients, it can be effectively used as a vaccine for cancer prevention.

Another aspect provides a preventive or therapeutic agent for cancer comprising the peptide as an active ingredient.

Since the preventive or therapeutic agent for cancer according to an aspect contains the peptide as an active ingredient, a peptide that exists on the surface of cancer cells and helps immune cells to remove cancer cells binds to HLA-A02:01 to cause cancer cells in immune cells. Since it induces the immune system response to cells, that is, immunologic surveillance, it can be expected to be effective in cancer treatment efficiently.

When the peptide is prepared to be included as a preventive or therapeutic agent for cancer, the preventive or therapeutic agent for cancer may include a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the prophylactic or therapeutic agents are those commonly used in formulation, for example, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin. , calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, etc. It is not limited. The preventive or therapeutic agent for cancer may further include, for example, a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like, in addition to the above components.

The preventive or therapeutic agent for cancer may be administered orally or parenterally. In the case of parenteral administration, for example, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endothelial administration, local administration, intranasal administration, intrapulmonary administration, rectal administration, etc. can be administered. Since the protein or peptide is digested upon oral administration, oral compositions should be formulated to coat the active agent or to protect it from degradation in the stomach. In addition, the composition may be administered by any device capable of transporting the active agent to a target cell.

A suitable dosage of the cancer prevention or therapeutic agent is variously prescribed depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity. can be A preferred dosage of the composition may be in the range of, for example, 0.001-100 mg/kg on an adult basis. The term "pharmaceutically effective amount" means an amount sufficient to prevent or treat cancer, or to prevent or treat a disease caused by cancer.

The preventive or therapeutic agent for cancer may be prepared in a unit dosage form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method readily practiced by a person skilled in the art, or prepared by introducing into a multi-dose container. can In this case, the formulation may be in the form of a solution, suspension, syrup, or emulsion in oil or an aqueous medium, or may be in the form of an extract, powder, powder, granule, tablet or capsule, and may additionally include a dispersant or stabilizer.

In addition, the composition may be administered as an individual therapeutic agent or in combination with a therapy conventionally used to treat, prevent or treat cancer. The composition may be administered in combination with therapy, and may be administered sequentially or simultaneously with conventional therapy.

Examples of conventional therapies include, but are not limited to, surgery, chemotherapy, radiation therapy, hormone therapy, biological therapy, and immunotherapy. In addition, the prophylactic or therapeutic agent for cancer of the present invention can be used to prevent or treat cancer-related diseases or disorders, and a specific drug or a therapeutically or prophylactically effective amount for a patient in need of such treatment or prevention or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, clathrate or prodrug thereof. The preventive or therapeutic agent for cancer is administered in combination with another drug (“tea drug”) or a method for treating, treating or preventing cancer. The type of the secondary drug is not limited, and may be a protein, antibody, small molecule drug, liposome, nanoparticles, stem cell, or the like.

Another aspect provides a composition for diagnosis of cancer comprising the peptide as an active ingredient.

The term “diagnosing” as used refers to ascertaining the presence or characteristics of pathophysiology. Diagnosis within the present specification is to determine whether or not cancer has developed and progressed.

The peptide of one aspect may bind to a fluorescent substance for molecular imaging in order to diagnose cancer through imaging.

The fluorescent substance for molecular imaging refers to any material that generates fluorescence, for example, may be one that emits red or near-infrared fluorescence, and may be a fluorescent substance having a high quantum yield, but this not limited

The fluorescent substance for molecular imaging may be, for example, a fluorescent protein or other imaging material, but is not limited thereto.

The phosphor may be, for example, fluorescein, BODYPY, tetramethylrhodamine, Alexa, cyanine, allopicocyanine, or a derivative thereof. However, it is not limited thereto.

The fluorescent protein may be, for example, Dronpa protein, green fluorescent protein (EGFP), red fluorescent protein (DsRFP), Cy5.5, which is a cyanine fluorescent protein exhibiting near-infrared fluorescence, or other fluorescent protein, but is not limited thereto. does not

The other imaging material may be, for example, iron oxide or a radioactive isotope, but is not limited thereto, and may be applied to imaging equipment such as MRI and PET.

Overlapping content is omitted in consideration of the complexity of the present specification, and terms not defined otherwise in the present specification have the meanings commonly used in the art to which the present invention pertains.

Hereinafter, the present invention will be described in more detail through examples. However, these examples are provided and the scope of the present invention is not limited to these examples.

[Example]

Example 1. Purification and analysis of peptides that specifically bind to cancer cell expression HLA-A02:01

In order to identify a common cancer antigen, a peptide obtained through an immunoprecipitation reaction (Immunoprecipitation: IP) between Peptidom and MHC for peptidom binding to human leukocyte antigen (HLA) expressed in cancer tissues was analyzed. 180-400 mg of frozen triple negative breast cancer (TNBC) patient's tissue is shredded with a crusher (CP02 cryoPREP Automated Dry Pulverizer), and 1 mL of lysed solution (1% octyl glucoside, 0.25% sodium Sodium deoxycholate, 1 mM ethylenediaminetetraacetic acid (EDTA), 1 mM phenylmethanesulforyl fluoride (PMSF), 0.2 mM iodoacetamide, protease inhibitor cocktail and Phosphate-buffered saline (PBS)) was added and allowed to stand for 1 hour, followed by centrifugation at 17,000 rpm at 4 °C for 20 minutes. After that, the supernatant was separated and reacted with 50 μL of HLA-antibody-resin at 4 °C for 2 hours. Then, wash solution A (pH 8.0) consisting of 150 mM NaCl and 20 mM Tris-HCl, wash solution B (pH 8.0) consisting of 400 mM NaCl and 20 mM Tris-HCl, wash solution A and 20 mM Tris-HCl washing solution C (pH 8.0) was washed by treating the resin with 300 μL of the solution 3 times in the order. Then, it was eluted 8 times with 100 μL of 0.1 M acetic acid solution, and the eluted solution was purified using tC18 resin. After that, the peptide was finally eluted with 30% acetonitrile and 0.1% trifluoroacetic acid (TFA) solution, dried, dissolved in 0.1% formic acid solution, and analyzed by Q Exactive mass spectrometry mass spectrometry. The analysis was performed, and the obtained mass spectrometry data was analyzed using the MaxQuant program to identify a peptide that specifically binds to HLA. Peptide analysis conditions were set as unspecific for enzyme specificity, a false discovery rate of 0.01, a peptide length of 8 to 15, a maximum peptide mass of 1,500 kDa, and a maximum charge of 3.

A total of about 1,000 candidate peptides were determined through analysis of the peptidome obtained after the immunoprecipitation reaction between the peptidome and MHC.

Example 2. Determination of a peptide cancer-associated antigen that specifically binds to HLA-A02:01

In order to find a common cancer antigen for use in vaccines that can prevent or treat cancer was carried out. An experiment was performed to select a common cancer antigen candidate peptide from among the 1000 types of primary candidate group peptides obtained in Example 1. The identified peptides were analyzed for affinity for each HLA-A02:01 allele using the NetMHC (https://www.cbs.dtu.dk/services/NetMHC/) program. In addition, for each peptide, the immunogenicity of about 1000 kinds of peptides obtained in Example 1 was analyzed using the IEDB Analysis Resource (https://tools.iedb.org/immunogenicity/) program.

A total of 20 peptides were selected as cancer-related antigens _{having an affinity (IC 50} ) of 500 nM or less for HLA-A02:01 among the peptides based on the bioinformatics analysis of the candidate peptides analyzed above.

The 20 types of peptides that specifically bind to HLA-A02:01, which are commonly overexpressed in cancer tissues, found in this Example are present on the surface of cancer cells and specifically bind to HLA-A02:01, so that immune cells become cancer cells. It can be confirmed that it can effectively remove cancer cells because it can help to remove cancer cells and induce the immune system response to cancer cells and at the same time increase the immunogenicity of T cells.

<110> KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY THE ASAN FOUNDATION University of Ulsan Foundation For Industry Cooperation <120> Human leukocyte antigen A02:01 allele specific binding peptides and uses it <130> PN126045KR <160> 20 <170> KoPatentIn 3.0 <210> 1 <211> 9 <212> PRT <213> Unknown <220> <223> Phosphatidylinositol 4-kinase beta <400> 1 Lys Leu Tyr Asp Gly Phe Gln Tyr Leu 1 5 <210> 2 <211> 9 <212> PRT <213> Unknown <220> <223> Probable tRNA N6-adenosine threonylcarbamoyltransferase <400> 2 Lys Leu Val Glu Leu Pro Tyr Thr Val 1 5 <210> 3 <211> 9 <212> PRT <213> Unknown <220> <223> Integrator complex subunit 4 <400> 3 Ala Leu Gln Glu Lys Leu Trp Asn Val 1 5 <210> 4 <211> 9 <212> PRT <213> Unknown <220> <223> Translational activator GCN1 <400> 4 Ser Leu Leu Asp Pro Val Pro Glu Val 1 5 <210> 5 <211> 9 <212> PRT <213> Unknown <220> <223> Transformation/transcription domain-associated protein <400> 5 Thr Leu Ala Asp Leu Val His His Val 1 5 <210> 6 <211> 9 <212> PRT <213> Unknown <220> <223> DCC-interacting protein 13-alpha <400> 6 Phe Leu Ala Asn Ile Gly Thr Ser Val 1 5 <210> 7 <211> 9 <212> PRT <213> Unknown <220> <223> Propionyl-CoA carboxylase beta chain, mitochondrial <400> 7 Asn Met Val Asp Ile Ile His Ser Val 1 5 <210> 8 <211> 9 <212> PRT <213> Unknown <220> <223> Steroid receptor RNA activator 1 <400> 8 Leu Met Val Asp His Val Thr Glu Val 1 5 <210> 9 <211> 9 <212> PRT <213> Unknown <220> <223> Protein C12orf4 <400> 9 Asn Met Leu Pro Gln Ile Phe Arg Val 1 5 <210> 10 <211> 9 <212> PRT <213> Unknown <220> <223> Protein furry homolog <400> 10 Lys Leu Ile Gly Gln Val His Glu Val 1 5 <210> 11 <211> 9 <212> PRT <213> Unknown <220> <223> TOX high mobility group box family member 4 <400> 11 Met Ile Thr Asp Val Val Pro Glu Val 1 5 <210> 12 <211> 9 <212> PRT <213> Unknown <220> <223> DNA polymerase alpha subunit B <400> 12 Ala Leu Ile Glu Lys Leu Val Glu Leu 1 5 <210> 13 <211> 9 <212> PRT <213> Unknown <220> <223> PHD finger protein 3 <400> 13 Gly Gln Ile Glu Val Val Pro Glu Val 1 5 <210> 14 <211> 9 <212> PRT <213> Unknown <220> <223> Germinal-center associated nuclear protein <400> 14 Ser Leu Ser Ala Phe Thr Pro Ala Leu 1 5 <210> 15 <211> 9 <212> PRT <213> Unknown <220> <223> Fibronectin type III domain-containing protein 3B <400> 15 Ile Leu Trp Glu Thr Val Pro Ser Met 1 5 <210> 16 <211> 9 <212> PRT <213> Unknown <220> <223> Tensin-3 <400> 16 Tyr Ile Thr Glu Arg Ile Ile Ala Val 1 5 <210> 17 <211> 9 <212> PRT <213> Unknown <220> <223> NudC domain-containing protein 3 <400> 17 Ala Leu Leu Gly Ile Leu Gln His Val 1 5 <210> 18 <211> 9 <212> PRT <213> Unknown <220> <223> Apolipoprotein L3 <400> 18 Ala Leu Ala Asn Gly Ile Glu Glu Val 1 5 <210> 19 <211> 9 <212> PRT <213> Unknown <220> <223> Long chain fatty acid CoA ligase 3 <400> 19 Gly Met Ala Glu Arg Ile Pro Glu Leu 1 5 <210> 20 <211> 9 <212> PRT <213> Unknown <220> <223> DNA repair protein complementing XP-G cells <400> 20 Tyr Leu Asn Gln His Ile Glu His Val 1 5

Claims (9)

A peptide that specifically binds to the human leucocyte antigen (HLA) A02:01 allele of cancer cells,
The peptide is composed of the amino acid sequence of SEQ ID NO: 2, and the peptide has an affinity for HLA (IC ₅₀ ) of 500 nM or less. The peptide of claim 1, wherein the peptide is a cancer-associated antigen, a cancer-specific antigen, or a neoantigen. delete delete The peptide according to claim 1, wherein the peptide exhibits T cell-specific immunogenicity. The method according to claim 1, wherein the cancer is lung cancer, laryngeal cancer, stomach cancer, colon/rectal cancer, liver cancer, gallbladder cancer, pancreatic cancer, breast cancer, ovarian cancer, uterine cancer, cervical cancer, prostate cancer, carcinoma derived from epithelial cells, such as kidney cancer, skin cancer ( Carcinoma), bone cancer, muscle cancer, adipose cancer, sarcoma derived from connective tissue cells such as fibroblast cancer, hematopoietic cancer derived from hematopoietic cells such as leukemia, lymphoma, multiple myeloma, tumors occurring in nerve tissue, And triple negative breast cancer (Triple negative breast cancer) will at least one selected from the group consisting of, the peptide. A vaccine composition comprising the peptide of any one of claims 1, 2, 5 to 6 as an active ingredient. A preventive or therapeutic agent for cancer comprising the peptide of any one of claims 1, 2, 5 to 6 as an active ingredient. A composition for diagnosis of cancer comprising the peptide of any one of claims 1, 2, 5 to 6 as an active ingredient.

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