KR102215578B1 - Human leukocyte antigen specific binding peptides and uses thereof - Google Patents

Abstract

It relates to a peptide that specifically binds to a human leucocyte antigen (HLA) 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. Peptides that specifically bind to human leucocyte antigen (HLA) of cancer cells according to one aspect have high immunogenicity, so using them can induce a cellular immune response against cancer tissues expressing the HLA. It can be used as a vaccine for cancer treatment. Therefore, the peptide according to one aspect can ultimately be used as a therapeutic agent capable of preventing or treating cancer. In addition, the peptide according to an aspect can specifically bind to cancer cells, so that cancer can be diagnosed.

Description

Peptides specifically binding to human leukocyte antigens and uses thereof {Human leukocyte antigen specific binding peptides and uses thereof}

It relates to a peptide that specifically binds to a human leucocyte antigen (HLA) 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.

Compared to normal cells, cancer is not regulated in cell growth, can invade adjacent tissues, and sometimes metastasizes. Cancer is basically a disease related to tissue growth regulation, and when normal cells are transformed into cancer cells, the expression of genes that control cell growth and division changes (Croce., The New England Journal of Medicine, 358 (5): 502-511, 2008).

Anti-cancer therapy involves physically removing cancer tissue, or by irradiation or administration of anticancer drugs, including oncogenes, anti-apoptotic molecules, telomerases, and growth factor receptor genes ( It is carried out in a way that inhibits the expression of genes necessary for the survival of cancer cells, such as growth factor receptor gene and signaling molecule, or induces cell death (Knudson AG, Nature reviews. Cancer 1(2): 157-162, 2001). However, in such a treatment process, not only cancer cells but also normal cells may be affected, causing side effects.

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

Since many cancer antigens are immune-accepting agents as autoantigens, it is difficult to induce a specific immune response, and it is not easy to find antigens that can act in common in many cancers, in particular. However, the use of an antigenic peptide that induces a specific immune response against cancer cells may be useful in immunotherapy to specifically remove cancer cells expressing the antigen, but there is no known about this.

One aspect provides a peptide that specifically binds to a human leucocyte antigen (HLA) of cancer cells.

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

Another aspect provides a cancer prevention or treatment 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, a peptide that specifically binds to a human leucocyte antigen (HLA) of cancer cells is provided.

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

It provides a cancer prevention or treatment comprising the peptide as an active ingredient.

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

Peptides that specifically bind to human leucocyte antigen (HLA) of cancer cells according to one aspect have high immunogenicity, so using them can induce a cellular immune response against cancer tissues expressing the HLA. It can be used as a vaccine for cancer treatment. Therefore, the peptide according to an aspect can be ultimately used as a therapeutic agent capable of preventing or treating cancer. In addition, the peptide according to an aspect can specifically bind to cancer cells, so that cancer can be diagnosed.

1 is a schematic diagram of a simple method of obtaining a peptide having a high affinity for a human leukocyte antigen commonly expressed from cancer tissues of a cancer patient.
2 is a diagram showing the results of confirming the immunogenicity shown by treating peripheral blood mononuclear cells with a final cancer antigen peptide candidate group capable of specifically binding to the A11:01 allele.
Figure 3 is a result of confirming the immunogenicity for two kinds of peptides among the candidate cancer antigen peptides selected for PBMC cells (Fig. 3A) and an image confirming the immunogenicity for 20 kinds of candidate peptides as a quantitative graph of the degree of immunogenicity for each peptide It is a figure shown in the shown result (FIG. 3B).
FIG. 4 is a diagram showing the results of confirming the immunogenicity for CDC5L, ELF4A1, TCP1, and CTNNB1, which were finally selected as four peptides capable of specifically binding to the A11:01 allele.

One aspect provides a peptide that specifically binds to a human leucocyte antigen (HLA) of cancer cells.

The term “Human leukocyte antigen (HLA) is a gene complex that encodes a major histocompatibility complex (MHC) protein in humans, and refers to a chromosome 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 tissue compatibility complexes, and MHC and HLA may be used interchangeably in the present specification.

As used herein, the term "cancer" refers to a physiological condition characterized by unregulated cell growth in mammals or describes such a physiological condition, which infiltrates the surrounding tissues while growing rapidly and spreads or metastases to various parts of the body. It can contain, without limitation, life-threatening malignant tumors. Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma and leukemia or lymphoid malignancies. More specific examples of such cancers include carcinoma derived from epithelial cells such as 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, kidney cancer, and skin cancer. ), sarcoma derived from connective tissue cells such as bone cancer, muscle cancer, fat cancer, fibroblast cancer, hematopoietic cells such as leukemia, lymphoma, multiple myeloma, and tumors occurring in nerve tissues, and There are not only triple negative breast cancer, but also head and neck cancer.

The peptide according to an aspect may be a cancer common antigen (Tumor Associated self-antigen: TAA) or a neoantigen (Neoantigen). Cancer cell growth is known to occur when there is a defect in the immune system that identifies it as non-self and eliminates it. TAA is an antigen found in cancer cells and is not known to be found in normal cells. In addition, the TAA is known to appear as a result of DNA mutation caused by a carcinogen or as a result of expression of a genetic material by a carcinogenic DNA virus or an RNA virus. Therefore, 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, and induces a response of the immune system to cancer cells, that is, immunologic surveillance, thereby preventing cancer cells. Can be removed.

In addition, the neoantigen is referred to as a neoantigen, and the neoantigen refers to a mutation-based peptide sequence expressed by somatic mutation in cancer tissues. It is known that the neoantigen can occur in somatic mutations such as viral proteins, post-translational or point mutations, indels, or changes in open reading frames. The neoantigen is a common neoantigen and is not found in the normal genome, but a shared neoantigen that is common among specific cancer types or patients, and a personalized neoantigen that appears because the mutation location or information varies depending on the individual cancer patient ( personalized neoantigen) has two subgroups, and in one aspect, the neoantigen may include the common neoantigen and the personalized neoantigen.

The HLA may be class 1 or class 2, and class 1 of the HLA may include HLA-A, HLA-B, and HLA-C, and the HLA class 2 may include HLA-DR and HLA-DQ. Can include. In one aspect, a peptide specifically binding to the A11:01 allele among HLA class 1, which is most commonly expressed in triple negative breast cancer patients, was identified.

A peptide according to an aspect may consist of 5 to 50 amino acids, and may include, for example, 8 to 15 amino acids.

The peptide according to one aspect may be composed of SEQ ID NOs: 1 to 4, but any peptide capable of enhancing the immunogenicity of T cells while specifically binding to A11:01 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 one aspect, four kinds of CDC5L, ELF4A1, TCP1 and CTNNB1 peptides that specifically bind to the A11:01 allele of HLA class 1 were identified.

In one aspect, by crushing cancer tissue and dissolving it with a lysate, an immunoprecipitation reaction through HLA-antibody-resin expressed in the cancer tissue and peptidome binding thereto is performed, using tC18 resin. , Purified and purified peptides are common to primary cancer with the enzyme specificity as unspecific, the false discovery rate as 0.01, the peptide length as 8 to 15, the maximum peptide mass as 1,500, and the maximum charge as 3 The antigenic peptide was selected.

Subsequently, in a specific example, the affinity for each HLA allele was analyzed using the NetMHC (http://www.cbs.dtu.dk/services/NetMHC/) program, and the IEDB Analysis Resource (http:// tools.iedb.org/immunogenicity/) The top 50 peptides were selected by analyzing the immunogenicity of the primary cancer common antigen peptide obtained by the program, and in order to select the final antigenic peptide, intracellular staining method Using a high-volume, ultra-fast imaging-based experiment for detection of intracellular INF-γ markers, it is possible to easily perform CD8+ cell-mediated immunogenicity screening, so that it binds specifically to HLA in cancer cell tissues and at the same time has high immunogenicity. Four kinds of CDC5L, ELF4A1, TCP1 and CTNNB1 peptides according to one aspect were identified.

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

The vaccine composition may additionally include a buffering agent, an isotonic agent, a preservative, a stabilizer and a solubilizing agent. As the buffering agent, 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 substance.

The vaccine can induce a high cellular immune response as well as an antigen-specific humoral 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 with HLA, and the reaction of the immune system to cancer cells, that is, immunologic surveillance. ), so it can be used as a vaccine that can effectively prevent cancer. Therefore, the peptide specifically binds to A11:01 HLA, 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 it is not sensitive to the expression of heterologous cancer antigens, it can be effectively used as a vaccine for the prevention of cancer.

Another aspect provides a cancer prevention or treatment comprising the peptide or a combination thereof as an active ingredient.

The prevention or treatment of cancer according to one aspect contains the peptide as an active ingredient, so that the peptide that exists on the surface of the cancer cell and helps the immune cell to remove the cancer cell binds to HLA, and the immune system against the cancer cell of the immune cell Because it induces a response, that is, immunologic surveillance, it can be expected to have a high effect on effective cancer treatment.

When the peptide is prepared by being included as a prophylactic or therapeutic agent for cancer, the prophylactic 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 at the time of formulation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin. , Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, etc. It is not limited. The cancer prevention or treatment may further include, for example, a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components.

The cancer prevention or treatment may be administered orally or parenterally. In the case of parenteral administration, for example, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endothelial administration, topical administration, intranasal administration, intrapulmonary administration, and rectal administration may be used. When administered orally, since the protein or peptide is digested, the oral composition should be coated with an active agent or formulated to protect it from degradation in the stomach. In addition, the composition can be administered by any device capable of moving the active substance to the target cell.

The appropriate dosage for the prevention or treatment of cancer may be prescribed in various ways depending on factors such as formulation method, administration mode, age, weight, sex, pathological condition, food, administration time, route of administration, 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 diseases caused by cancer.

The cancer prevention or treatment may be prepared in a unit dosage form by formulation using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily practiced by those skilled in the art, or by introducing it into a multi-dose container. I can. At this time, the formulation may be in the form of a solution, suspension, syrup, or emulsion in an oil or aqueous medium, or in the form of an extract, powder, powder, granule, tablet or capsule, and may additionally include a dispersant or a stabilizer.

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

Examples of conventional treatments include, but are not limited to, surgery, chemotherapy, radiation therapy, hormone therapy, biological therapy, and immunotherapy. In addition, the prevention or treatment of cancer of the present invention can be used to prevent or treat a disease or disorder associated with cancer, such treatment, or a specific drug in an amount that is therapeutically or prophylactically effective for a patient in need of such treatment or Or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, clathrate or prodrug thereof. The prevention or treatment of cancer is administered in combination with other drugs (“secondary drugs”) or a method of treating, treating or preventing cancer. The type of secondary drug is not limited, and may be a protein, an antibody, a small molecule drug, a liposome, a nanoparticle, or a stem cell.

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

As used, the term "diagnosis" means to ascertain the presence or character of the pathophysiology. Diagnosis within this specification is to confirm the onset and course of cancer.

The peptide of one aspect may be combined with a fluorescent substance for molecular imaging in order to diagnose cancer through an image.

The molecular imaging phosphor refers to any material that generates fluorescence, and may emit red or near-infrared fluorescence, and may be a phosphor having a high quantum yield. Not limited.

The phosphor for molecular imaging may be, for example, a fluorescent protein or other imaging material, but is not limited thereto. The phosphor capable of binding to the peptide specifically binding to the A11:01 HLA may be, for example.

The phosphor is, 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, a Dronpa protein, a fluorescent gene (EGFP), a red fluorescent protein (DsRFP), a cyanine phosphor showing near-infrared fluorescence, Cy5.5, or other fluorescent protein, but is not limited thereto. Does not.

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

Redundant content is omitted in consideration of the complexity of the present specification, and terms not otherwise defined herein have meanings commonly used in the technical field to which the present invention belongs.

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

[Example]

Example 1. Purification and analysis of peptides specifically binding to HLA expressed in cancer cells

In order to identify common cancer antigens, peptides obtained through immunoprecipitation (IP) between peptidom-MHC and peptidom binding to human leukocyte antigen (HLA) expressed in cancer tissue were analyzed. 41 mg of frozen triple negative breast cancer (TNBC) patient's tissue was crushed with a crusher (CP02 cryoPREP Automated Dry Pulverizer) and 600 μL of lysate (1% octyl glucoside, 0.25% sodium D Oxycholate (sodium deoxycholate), 1 mM ethylenediaminetetraacetic acid (EDTA), 1 mM phenylmethanesulforyl fluoride (PMSF), 0.2 mM iodoacetamide, protease inhibitor cocktail and phosphoric acid Buffered saline (PBS)) was added and allowed to stand for 1 hour, followed by centrifugation at 15,000 rpm at 4°C for 20 minutes. Then, the supernatant was separated and reacted with 50 μL of A11:01 HLA-antibody-resin at 4°C for 2 hours. Thereafter, washing solution A (pH 8.0) consisting of 150 mM NaCl and 20 mM Tris-HCl, washing solution B (pH 8.0) consisting of 400 mM NaCl and 20 mM Tris-HCl, and 20 mM Tris-HCl Washing solution C (pH 8.0), 300 μL of the solution was treated with resin 3 times in order and washed. Then, it was eluted eight times with 100 μL of 0.1 M acetic acid solution, and the eluted solution was purified using tC18 resin. After that, the finally purified peptide was eluted with a 30% acetonitrile and 0.1% trifluoroacetic acid (TFA) solution, dried, and dissolved in a 0.1% formic acid (formic acid) solution to LTQ-Orbitrap. It was analyzed by mass spectrometry, and the obtained mass spectrometry data was analyzed using the MaxQuant program to identify a peptide that specifically binds to HLA. As for the analysis conditions of the peptide, the enzyme specificity was unspecific, the false discovery rate was 0.01, the peptide length was 8-15, the maximum peptide mass was 1,500, and the maximum charge was 3.

A total of 1000 peptides were determined through the analysis of peptidome obtained after the immunoprecipitation reaction between the peptidome and MHC.

Example 2. Selection of common cancer antigen candidate peptides

An experiment was performed to select a common cancer antigen candidate peptide among the 1,000 peptides of the primary candidate group obtained in Example 1. The identified peptides were analyzed for affinity for each A11:01 HLA allele using the NetMHC (http://www.cbs.dtu.dk/services/NetMHC/) program. In addition, for each peptide, the immunogenicity of 1,000 kinds of peptides obtained in Example 1 was analyzed by the IEDB Analysis Resource (http://tools.iedb.org/immunogenicity/) program. Based on the above analysis, candidates were selected in the order of high immunogenicity among peptides derived from cancer tissues. The finally selected candidate peptides were selected for the top 50 peptides with an affinity for A11:01 of 500 nM or less based on bioinformatics analysis.

Example 3. Selection of the final common cancer antigen peptide and verification thereof

The 50 peptides selected in Example 2 were subjected to a screening experiment to determine common cancer antigen peptides using an immunogenic screening system. Treatment conditions for the peptides selected in Example 2 are as follows: Using 384 wells, 50 μl of 5 X 10 ⁴ PBMC cells were inoculated for each well, and then 20 ug/ml of the peptides selected in 5 repetitions Contacted the cells. Thereafter, 20 ng/ml of IL-7 was added to the cell culture solution and cultured. At this time, in the positive group for immunogenicity, T cells were activated by treatment with CD3/CD28 beads (B:C = 1:2) (Stem cell, USA), whereas in the negative control group, only PBS buffer containing no peptides Processed. PBMC cells contacted with the peptide were cultured in a medium containing 100 U of IL-2, replaced with a new medium every 3 days, and cultured for about 1 week.

Subsequently, an imaging experiment for detection of an intracellular INF-γ marker was performed using an intracellular staining method for CD8+ cell mediated immunogenicity screening. In the positive group, immediately before performing intracellular staining in order to increase intracellular INF-γ excretion, cells were treated with PMA at a final concentration of 20 ng/ml and ionomycin at a final concentration of 1 μg/ml. In order to suppress cytokines secreted out of cells other than INF-γ, BFA (Biolegend) diluted at 1:000 magnification was treated on the cells for about 8 hours, and then the cells were fixed with 4% PFA/PERM buffer (BD, USA). . Thereafter, after puncturing the cell membrane, the intracellular staining method was performed. In order to detect CD8A, INF-γ, and CD4, which are intracellular staining markers, CD8a-alexa 488 (BD), INF-γ-APC (Biolegend), and CD4-alexa549 antibodies were diluted 1:50 at 4°C. After treatment overnight, it was washed 3 times with PBS. After washing, 20 μl of PBS to which 60 nM of DAPI was added was treated, and imaged using Operetta (Perkin Elmer) imaging system equipment, and the result of INF-γ detection confirmed by imaging is shown in FIG. 2. CD8+ T cells were labeled in green and cells secreting INF-γ in red.

As shown in FIG. 2, it was confirmed that the common antigen can be efficiently selected by the difference in expression of the cells when the candidate peptide is treated through PBMC cells stained in green and red. In particular, it was confirmed that INF-γ was detected in a large amount in the positive group, whereas INF-γ was hardly detected in the negative control group. Therefore, through the analysis of the expression difference as described above, it is possible to effectively confirm whether the candidate peptide is effectively immunogenic, and thus, it is possible to screen for a peptide that specifically binds to A11:01 HLA, which is commonly expressed in cancer tissues. Was confirmed.

Example 4. Immunogenicity Verification for Common Cancer Antigen Peptides That Specifically Bind to A11:01

In order to find a common cancer antigen, an experiment was conducted to verify the immunogenicity of a peptide that specifically binds to A11:01, which is commonly overexpressed in tissues of TNBC patients. Using PBMC cells derived from three donors expressing A11:01, the experimental methods disclosed in Examples 1 to 3 were performed. In intracellular staining for immunogenicity, CD8+ T cells were labeled green, cells secreting INF-γ were labeled red, and cells with CD4 were labeled purple. Fig. 3A shows the results of confirming the immunogenicity of two peptides among the candidate cancer antigen peptides selected for PBMC cells derived from three donors, and an image confirming the immunogenicity of 20 candidate peptides. The results shown in a quantitative graph are shown in Fig. 3B. The result of confirming the immunogenicity of CDC5L, ELF4A1, TCP1 and CTNNB1, which was finally selected as the four most immunogenic peptides among the peptides that specifically bind to A11:01 among a total of 50 peptide candidate groups, is shown. It is shown in 4.

As shown in FIG. 3A, when the selected candidate peptide is treated in PBMC cells with A11:01, the peptides of TCP1 and CTNNB1 show immunogenicity by detecting INF-γ expressed for each of the treated peptides. It was confirmed that it can be a common cancer antigen peptide. As confirmed in FIG. 3B, it was confirmed that P12 of the 20 candidate peptides showed a high degree of immunogenicity in all PBMCs derived from different types. It was confirmed in FIG. 4 that CDC5L, ELF4A1, TCP1, and CTNNB1, finally selected through a screening process for peptides with high immunogenicity among the candidate peptides identified by the processes of FIGS. 3A and 3B, exhibit a higher degree of immunogenicity compared to the negative control group. I did. Therefore, it was confirmed that four kinds of CDC5L, ELF4A1, TCP1 and CTNNB1 peptides that specifically bind to A11:01 HLA, which are overexpressed in general cancer tissues, can be selected, and the peptides exist on the surface of cancer cells and are specific. By binding to A11:01 HLA, it helps immune cells remove cancer cells, inducing a response of the immune system to cancer cells of the immune cells, and at the same time enhancing the immunogenicity of T cells, thus effectively removing cancer cells. Confirmed that there is.

<110> KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY Korea University Research and Business Foundation <120> Human leukocyte antigen specific binding peptides and uses thereof <130> PN126044 <160> 4 <170> KoPatentIn 3.0 <210> 1 <211> 9 <212> PRT <213> Unknown <220> <223> Amino acid sequence of CDC5L <400> 1 Arg Thr Ile Ala Pro Ile Ile Gly Arg 1 5 <210> 2 <211> 9 <212> PRT <213> Unknown <220> <223> Amino acid sequence of ELF4A1 <400> 2 Gly Ile Tyr Ala Tyr Gly Phe Glu Lys 1 5 <210> 3 <211> 9 <212> PRT <213> Unknown <220> <223> Amino acid sequence of TCP1 <400> 3 Gly Val Phe Glu Pro Thr Ile Val Lys 1 5 <210> 4 <211> 9 <212> PRT <213> Unknown <220> <223> Amino acid sequence of CTNNB1 <400> 4 Gln Val Ala Asp Lys Asp Gly Gln Tyr 1 5

Claims (11)

A peptide that specifically binds to a human leucocyte antigen (HLA) of cancer cells, wherein the peptide consists of any one of SEQ ID NOs: 2 to 4. The peptide according to claim 1, wherein the peptide is a cancer common antigen or a neoantigen. The peptide of claim 1, wherein the HLA is class 1. The peptide of claim 1, wherein the HLA is an A11:01 allele. delete The peptide of claim 1, wherein the peptide has an affinity for HLA of 500 nM or less. The peptide of claim 1, wherein the peptide exhibits T cell-specific immunogenicity. The method according to claim 1, wherein the cancer is carcinoma derived from epithelial cells such as lung cancer, laryngeal cancer, gastric cancer, colon/rectal cancer, liver cancer, gallbladder cancer, pancreatic cancer, breast cancer, ovarian cancer, uterine cancer, cervical cancer, prostate cancer, kidney cancer, and skin cancer ( carcinoma), bone cancer, muscle cancer, fat cancer, sarcoma derived from connective tissue cells such as fibroblast cancer, blood cancer derived from hematopoietic cells such as leukemia, lymphoma, and multiple myeloma, tumors occurring in nerve tissues, And triple negative breast cancer (Triple negative breast cancer) is one or more peptides selected from the group consisting of. A vaccine composition comprising the peptide of any one of claims 1 to 4 and 6 to 8 or a combination thereof as an active ingredient. The prevention or treatment of cancer comprising the peptide of any one of claims 1 to 4 and 6 to 8 or a combination thereof as an active ingredient. A composition for diagnosis of cancer comprising the peptide of any one of claims 1 to 4 and 6 to 8 or a combination thereof as an active ingredient.

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