Pharmaceutical composition for preventing cancer comprising thymic cells or thymic epithelial cells as active ingredient

Abstract

The present invention relates to a pharmaceutical composition for preventing cancer comprising thymic cells or thymic epithelial cells as an active ingredient, and can prevent cancer by using thymic cells or thymic epithelial cells from childhood. The present invention can be helpfully utilized as a composition for preventing cancer in that thymic cells or thymic epithelial cells, which naturally degenerate after a certain period of time, can be used, and the extracted thymic cells or thymic epithelial cells can be easily treated through autograft.

Description

Pharmaceutical composition for preventing cancer comprising thymus cells or thymus epithelial cells as an active ingredient

[0001] The present invention relates to a pharmaceutical composition for preventing cancer comprising thymic cells or thymic epithelial cells as an active ingredient.

[0002] This invention claims priority to Republic of Korea Patent Application No. 10-2024-0004755, filed January 11, 2024, the entire disclosure of which is incorporated herein by reference.

[0003]

[0004] The thymus is an organ that develops bone marrow stem cells into mature T cells. Here, immature T cells undergo division and differentiation, and through this process, various types of T cells are selected. As T cells undergo differentiation, they express various types of cell membrane proteins, and ultimately, by expressing appropriate cell membrane proteins, they perform their functions. However, T cell differentiation must be strictly regulated to ensure normal immunity, and since the thymus performs this regulation, it is designated as a primary lymphoid organ responsible for T cell development and cultivation.

[0005] The thymus consists of two lobes, joined at the center and surrounded by a capsule that extends internally and contains blood vessels. The lobes consist of a densely packed outer cortex and a less dense inner cortex. The lobes are divided into smaller lobes, each 0.5–2 mm in diameter, with radial insertions extending from the capsule along the septum.

[0006] The cortex is primarily composed of thymocytes and epithelial cells. Thymocytes, immature T cells, are supported by a network of finely branched epithelial reticular cells, which form adventitious pathways to blood vessels, which enter the cortex through septa near the junction with the meninges. The thymus also contains other cells, including macrophages, dendritic cells, small numbers of B cells, neutrophils, and eosinophils.

[0007] Thymic epithelial cells (TECs) are a key component of the thymic stroma. TECs within the thymic cortex (cTECs) are specialized for T cell positive selection, whereas medullary TECs (mTECs) are involved in T cell negative selection. TEC-mediated selection promotes a highly diverse T cell repertoire, capable of recognizing foreign antigens presented by self-MHC molecules and allowing for self-tolerance. Normal thymogenesis involves a highly organized network of stromal cells and hematopoietic cell types in addition to TECs.

[0008] Meanwhile, cancer is one of humanity's most incurable diseases, and massive amounts of capital are being invested globally in the development of treatments. In Korea, it is the leading cause of death, with over 100,000 new cases diagnosed annually and over 60,000 deaths. Carcinogens, including smoking, ultraviolet rays, chemicals, food, and other environmental factors, are known to cause cancer. However, the diverse causes make developing treatments challenging, and the effectiveness of treatments varies depending on the site of the disease.

[0009] In particular, the development of preventive agents for cancer is more difficult and necessary than that of therapeutic agents for cancer due to limitations in experimental design and the long time required.

[0010]

[0011] One object of the present invention is to provide a pharmaceutical composition for preventing cancer, comprising at least one selected from the group consisting of thymocytes and thymic epithelial cells as an active ingredient.

[0012] Another object of the present invention is to provide a kit for preventing cancer, comprising a composition comprising at least one selected from the group consisting of thymocytes and thymic epithelial cells, and an instruction manual.

[0013] However, the technical problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by a person having ordinary skill in the technical field to which the present invention belongs from the description below.

[0014]

[0015] The present invention provides a pharmaceutical composition for preventing cancer, comprising at least one selected from the group consisting of thymocytes and thymic epithelial cells as an active ingredient.

[0016] In one embodiment of the present invention, the composition may be composed of, but is not limited to, thymocytes or thymic epithelial cells.

[0017] In one embodiment of the present invention, the composition may be autologous, but is not limited thereto.

[0018] In one embodiment of the present invention, the thymic epithelial cells express keratin, MHC class II, CD5 + TCRβ + , CD69 + TCRβ + It may express one or more markers selected from the group consisting of, but is not limited thereto.

[0019] In one embodiment of the present invention, the thymic epithelial cell may be, but is not limited to, a cortical thymic epithelial cell or a medullary thymic epithelial cell.

[0020] In one embodiment of the present invention, the cortical thymic epithelial cells may express one or more markers selected from the group consisting of aminopeptidase A (BP-1), C11, and CD205 (cortex specific keratin subunits), but are not limited thereto.

[0021] In one embodiment of the present invention, the medullary thymic epithelial cells may express one or more markers selected from the group consisting of Ep-CAM, K5, and UEA-1, but are not limited thereto.

[0022] In one embodiment of the present invention, the cancer may be at least one selected from the group consisting of skin cancer, breast cancer, colon cancer, stomach cancer, oral cancer, lung cancer, cervical cancer, uterine cancer, endometrial cancer, vaginal cancer, tonsil cancer, pharyngeal cancer, laryngeal cancer, brain tumor, liver cancer, pancreatic cancer, leukemia, esophageal cancer, prostate cancer, bladder cancer, ovarian cancer, pituitary adenoma, small intestine cancer, rectal cancer, colon cancer, thyroid cancer, lymphoma, and renal cell carcinoma, but is not limited thereto.

[0023] In one embodiment of the present invention, the composition may be characterized by at least one selected from the group consisting of, but not limited to:

[0024] a) Inhibition of epidermal thickness increase due to skin cancer;

[0025] b) reduction in the number of inflammatory cells; and

[0026] c) Immune system strengthening effect.

[0027] The present invention provides a cancer prevention kit comprising a composition comprising at least one selected from the group consisting of thymocytes and thymic epithelial cells, and an instruction manual.

[0028] In addition, the present invention provides a method for preventing cancer, comprising administering to a subject in need thereof a pharmaceutically effective amount of a composition comprising / consisting of at least one selected from the group consisting of thymocytes and thymic epithelial cells; or at least one selected from the group consisting of thymocytes and thymic epithelial cells as an active ingredient.

[0029] In addition, the present invention provides a use for cancer prevention of a composition comprising / consisting of at least one selected from the group consisting of thymocytes and thymic epithelial cells; or at least one selected from the group consisting of thymocytes and thymic epithelial cells; as an active ingredient.

[0030] In addition, the present invention provides a use for manufacturing a cancer prevention agent comprising a composition comprising / consisting of at least one selected from the group consisting of thymocytes and thymic epithelial cells; or at least one selected from the group consisting of thymocytes and thymic epithelial cells as an active ingredient.

[0031]

[0032] According to a pharmaceutical composition for preventing cancer comprising thymocytes or thymic epithelial cells as an active ingredient, cancer can be prevented using thymocytes or thymic epithelial cells from childhood. The present invention can be usefully utilized as a composition for preventing cancer because thymocytes or thymic epithelial cells can be used, which naturally degenerate after a certain period of time, and the extracted thymocytes or thymic epithelial cells can be easily processed through autologous transplantation.

[0033]

[0034] Figure 1 is a schematic diagram showing the production of a cancer-inducing mouse model to confirm the cancer-preventive effect of juvenile thymocytes or thymic epithelial cells.

[0035] Figure 2a shows the location where thymocytes extracted from the juvenile mouse model of the present invention were injected into the elderly mouse model.

[0036] Figure 2b shows the results of observing the thymus for 7 days after injecting thymocytes extracted from the juvenile mouse model of the present invention into an elderly mouse model.

[0037] Figures 3a to 3c illustrate the cancer-preventive effect of juvenile thymocytes or thymic epithelial cells. Figure 3a is an image showing the results of a morphological analysis of mice transplanted with juvenile thymocytes or thymic epithelial cells. Figures 3b and 3c show the results of an H&E analysis of mice transplanted with the above cells, showing that hyperplastic epidermis and infiltration of immune inflammatory cells, which accompany cancer induction, were significantly suppressed.

[0038]

[0039] The inventors of the present invention confirmed that skin cancer was prevented when thymocytes or thymic epithelial cells were administered to a mouse model, and it is expected that various types of cancer that can occur in old age can be prevented by collecting thymocytes or thymic epithelial cells from childhood and autologously transplanting them after puberty, thereby restoring the decline in the immune surveillance system, and thus completed the present invention.

[0040] The present invention provides a pharmaceutical composition for preventing cancer, comprising at least one selected from the group consisting of thymocytes and thymic epithelial cells as an active ingredient.

[0041] In one embodiment of the present invention, the composition may be composed of, but is not limited to, thymocytes or thymic epithelial cells.

[0042] In the present invention, thymocytes or thymic epithelial cells can prevent cancer by autologously transplanting only the cells collected in childhood without any other components. Therefore, the composition of the present invention may be characterized by being composed solely of thymocytes or thymic epithelial cells. In addition, the cancer prevention effect of the present invention may be enhanced through the addition of other active ingredients, but is not essential thereto.

[0043] In the present invention, thymocytes are interchangeably used as thymocytes, and can develop into T cells with immune capabilities through a maturation process in the thymus. T cells can be broadly classified into four types: killer T cells, helper T cells, regulatory T cells, and memory T cells. Therefore, the thymocytes of the present invention are not limited to specific T cells, and may refer to all types and compositions of thymocytes that can be collected from the thymus at the time of collection, and may be specified through biomarkers expressed by each T cell, but are not limited thereto.

[0044] In the present invention, thymic epithelial cells (TECs) may refer to specialized cells with a high degree of anatomical, phenotypic, and functional heterogeneity located in the outer layer (epithelium) of the thymic stroma. The thymus, a primary lymphoid organ, functions to mediate T cell development and maturation. The thymic microenvironment can be established by a network of TECs populated with thymocytes (blood cell precursors of T cells) at various developmental stages. In particular, TECs and thymocytes are the most important components of the thymus required for the production of functionally competent T lymphocytes and self-tolerance. In particular, various immunodeficiencies and autoimmune diseases can be induced by TEC dysfunction, including but not limited to these.

[0045] The thymus is a butterfly-shaped organ of the immune system located in the anterior mediastinum of the chest, producing T lymphocytes. The thymus reaches its largest size during puberty and gradually degenerates as we reach adulthood. In particular, the thymus, which consists of two triangular lobes, is at its largest relative to body weight immediately after birth and reaches its peak size of about 30-40 g during puberty. After that, it loses its function as it grows into an adult, and most of it is replaced by fat tissue. The decrease in thymus size continues throughout life, reaching about 6 g by the age of 70, and it is known that the function of the thymus degenerates as its size decreases.

[0046] In the present invention, thymocytes or thymic epithelial cells may include all those collected from the thymus before adulthood, and for example, may be collected from the thymus at a certain time around puberty, which is the period when the size and function are the best, but are not limited thereto, and any cells that can be collected from the thymus immediately after birth at any time that does not cause problems for the individual are not limited thereto.

[0047] In one embodiment of the present invention, the composition may be autologous, but is not limited thereto.

[0048] In the present invention, autotransplantation may refer to a process of transplanting tissues, organs, etc. from one site to another in the body of the same individual. Thymocytes or thymic epithelial cells collected from the thymus of the present invention may be collected from the same individual and autotransplanted into the thymus after a certain period of time, but are not limited thereto.

[0049] The thymus is characterized by its natural degeneration as an adult, and if it does not degenerate after adulthood, for example, if it does not atrophy abnormally or rather increases in size, it has the characteristic that myasthenia gravis or tumors may develop. However, in the present invention, it has been confirmed that cancer is prevented when thymocytes or thymic epithelial cells are autologously transplanted. Therefore, the composition comprising / consisting of thymocytes or thymic epithelial cells of the present invention as an active ingredient can be used as a pharmaceutical composition for preventing cancer that does not induce an immune response through autologous transplantation.

[0050] In one embodiment of the present invention, the thymic epithelial cells express keratin, MHC class II, CD5 + TCRβ + , CD69 + TCRβ + It may express one or more markers selected from the group consisting of, but is not limited thereto.

[0051] Immune tolerance refers to the body's non-responsiveness to self-antigens and is categorized into central and peripheral immune tolerance. Central immune tolerance can refer to the elimination of lymphocytes with receptors that react with self-antigens in primary lymphoid organs (B cells in the bone marrow, T cells in the thymus), while peripheral immune tolerance can refer to the elimination or silencing of lymphocytes with receptors that react with self-antigens in secondary lymphoid organs.

[0052] In the positive and negative selection of T cells, T cells sort out T cells with T cell receptors (TCRs) that can recognize self-MHC through the positive selection process, and eliminate T cells that strongly bind to self-MHC or MHC-self peptides through apoptosis through negative selection. This T cell selection process can form T cell tolerance. Through the differentiation process, T cells acquire T cell receptors that recognize their own antigens, but in some cases, the T cell receptors recognize their own antigens. Therefore, these T cells must be eliminated before they migrate out of the thymus to prevent autoimmune diseases. In other words, the thymus is a crucial organ that is involved not only in T cell differentiation but also in the selective removal of T cells that induce autoimmunity, and thymic epithelial cells can play a central role in this process. As aging progresses, structural changes in the thymus occur, and TCR diversity and naive T cell reduction may occur. The number of cortical thymic epithelial cells decreases, and thus the positive selection ability for T cell development decreases. At this time, the positive selection marker of T cells is CD5 + TCRβ + , CD69 + TCRβ + And, since the thymic epithelial cells of the present invention are collected from the thymus before it has degenerated into an adult, they can be identified by the positive selection marker described above, but are not limited thereto.

[0053] In one embodiment of the present invention, the thymic epithelial cell may be, but is not limited to, a cortical thymic epithelial cell or a medullary thymic epithelial cell.

[0054] In one embodiment of the present invention, the cortical thymic epithelial cells may express one or more markers selected from the group consisting of aminopeptidase A (BP-1), C11, and CD205 (cortex specific keratin subunits), but are not limited thereto.

[0055] In one embodiment of the present invention, the medullary thymic epithelial cells may express one or more markers selected from the group consisting of Ep-CAM, K5, and UEA-1, but are not limited thereto.

[0056] In the present invention, “cancer” is used with the same meaning as “tumor” and typically refers to a condition characterized by uncontrolled cell growth or proliferation.

[0057] In one embodiment of the present invention, the cancer may be at least one selected from the group consisting of skin cancer, breast cancer, colon cancer, stomach cancer, oral cancer, lung cancer, cervical cancer, uterine cancer, endometrial cancer, vaginal cancer, tonsil cancer, pharyngeal cancer, laryngeal cancer, brain tumor, liver cancer, pancreatic cancer, leukemia, esophageal cancer, prostate cancer, bladder cancer, ovarian cancer, pituitary adenoma, small intestine cancer, rectal cancer, colon cancer, thyroid cancer, lymphoma, and renal cell carcinoma, but is not limited thereto.

[0058] In the present invention, the preventive effect of thymocytes or thymic epithelial cells on skin cancer was confirmed as an example of cancer. In this case, skin cancer was induced by DMBA / TPA, and according to common knowledge in the art, DMBA / TPA is known to induce breast cancer, so it can be judged that breast cancer can be prevented by the method of the present invention. In addition, since breast cancer is described as an example of cancer that can be prevented in the present invention, like skin cancer, cancer in the present invention may include all cancers that can be caused by DMBA / TPA, including skin cancer and breast cancer, but is not limited thereto.

[0059] In the present invention, the cancer may be, but is not limited to, a cancer that does not occur in childhood but may appear in an individual in old age.

[0060] The skin is the outermost layer of the body, acting as a barrier to protect various organs and muscles from the external environment. It is the heaviest organ in the human body and also functions as an insulator and body temperature regulator. It also functions as a sensory organ for various stimuli, including temperature, pressure, and pain. It also stores lipids and water, and participates in vitamin D synthesis.

[0061] Skin cancer is a general term for all malignant tumors that form in skin tissue. Skin cancer is primarily caused by environmental stimuli such as ultraviolet rays, or genetic factors. It is known that a family history of skin cancer is influenced by several genes, including the KIT gene. However, the most significant factor is external stimuli such as ultraviolet rays. The incidence of skin cancer is gradually increasing due to factors such as the introduction of Western lifestyles, increased outdoor activities, increased use of suntan creams and tanning devices, and increased penetration of ultraviolet rays due to the weakening ozone layer. These environmental factors accumulate with age, leading to skin cancer. Therefore, preventing these carcinogenic effects in aging individuals is essential. Furthermore, the development of skin cancer can lead to, but is not limited to, abnormal cell division, thickening of the epidermis, and suppression of the immune response.

[0062] In one embodiment of the present invention, the composition may be characterized by at least one selected from the group consisting of, but not limited to:

[0063] a) Inhibition of epidermal thickness increase due to skin cancer;

[0064] b) reduction in the number of inflammatory cells; and

[0065] c) Immune system strengthening effect.

[0066] Furthermore, the thymocytes or thymic epithelial cells of the present invention may exhibit not only cancer prevention but also therapeutic effects. Therefore, the thymocytes or thymic epithelial cells extracted from the thymus of the present invention may be utilized as a cell therapy agent.

[0067] That is, the present invention provides a pharmaceutical composition for preventing or treating cancer, comprising thymocytes or thymic epithelial cells as an active ingredient. In addition, the present invention additionally provides a kit for preventing or treating cancer, comprising a composition comprising thymocytes or thymic epithelial cells as an active ingredient, and an instruction manual.

[0068] Cell therapy is a rapidly emerging field in the medical field that enables "fundamental treatment" using cells, especially stem cells, in areas previously thought to be limitedly treatable through drugs or surgery. In particular, in the field of regenerative medicine, it is a new technology field that combats diseases by regenerating or replacing tissues and organs damaged or dysfunctional due to aging, disease, or accidents, thereby restoring their function. It is also emerging as an alternative treatment for intractable diseases. For cell therapy to be widely used, the challenge of immune rejection must be overcome. However, the thymocytes or thymic epithelial cells of the present invention are characterized by being autologous, so they do not elicit an immune response and can be utilized as excellent cell therapy agents, but are not limited thereto.

[0069] Therefore, the thymocytes or thymic epithelial cells of the present invention can be stored for future autologous transplantation through methods commonly used in the art, for example, “banking.”

[0070] In the present invention, “banking” or “cell banking” may refer to a system for preserving cells, etc. that can be used for therapeutic purposes, for use in various fields. At this time, low-temperature storage methods, freezing methods, etc. are generally applied for preservation, but are not limited thereto. Here, “cryopreservation” refers to a process of preserving cells, tissues, or any other material that is sensitive to damage caused by time or enzymatic or chemical activity by cooling them to sub-zero temperatures and storing them. In addition, “cryobanking” in the art refers to a technique in which cells are mixed with a cryoprotectant (e.g., DMSO with or without hydroxyethyl starch (HES)) and placed in a container suitable for storage under low-temperature preservation conditions. These containers are then frozen using techniques well known in the art and stored at low temperatures, typically at about -130°C to about -196°C. The collection of cells obtained by this process is a cell bank.

[0071] Here, “bank” means a storage place for cells, and the stored cells can be used as is or differentiated for the individual or another individual for therapeutic, clinical or research purposes, as needed, but are not limited thereto.

[0072] The pharmaceutical composition according to the present invention may further comprise suitable carriers, excipients, and diluents commonly used in the manufacture of pharmaceutical compositions. The excipients may be, for example, one or more selected from the group consisting of diluents, binders, disintegrants, lubricants, adsorbents, moisturizers, film-coating materials, and controlled-release additives.

[0073] The pharmaceutical composition according to the present invention may be formulated and used in the form of external preparations such as powders, granules, sustained-release granules, enteric-coated granules, liquids, eye drops, ellipsoids, emulsions, suspensions, alcohols, troches, aromatic waters, limonades, tablets, sustained-release tablets, enteric-coated tablets, sublingual tablets, hard capsules, soft capsules, sustained-release capsules, enteric capsules, pills, tinctures, soft extracts, dry extracts, fluid extracts, injections, capsules, irrigation solutions, ointments, lotions, pastes, sprays, inhalants, patches, sterile injection solutions, or aerosols, according to a conventional method, and the external preparations may have formulations such as creams, gels, patches, sprays, ointments, ointments, lotions, liniments, pastes, or cataplasmas.

[0074] Carriers, excipients and diluents that may be included in the pharmaceutical composition according to the present invention include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

[0075] When formulating, it is usually prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants.

[0076] The additives of the tablets, powders, granules, capsules, pills, and troches according to the present invention include excipients such as corn starch, potato starch, wheat starch, lactose, sucrose, glucose, fructose, D-mannitol, precipitated calcium carbonate, synthetic aluminum silicate, calcium hydrogen phosphate, calcium sulfate, sodium chloride, sodium bicarbonate, purified lanolin, microcrystalline cellulose, dextrin, sodium alginate, methylcellulose, sodium carboxymethylcellulose, kaolin, urea, colloidal silica gel, hydroxypropyl starch, hydroxypropyl methylcellulose (HPMC) 1928, HPMC 2208, HPMC 2906, HPMC 2910, propylene glycol, casein, calcium lactate, and Primogel; Gelatin, gum arabic, ethanol, agar powder, cellulose acetate phthalate, carboxymethylcellulose, calcium carboxymethylcellulose, glucose, purified water, sodium caseinate, glycerin, stearic acid, sodium carboxymethylcellulose, sodium methylcellulose, methylcellulose, microcrystalline cellulose, dextrin, hydroxycellulose, hydroxypropyl starch, hydroxymethylcellulose, refined shellac, starch starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinyl pyrrolidone, and binders such as hydroxypropyl methylcellulose, corn starch, agar powder, methylcellulose, bentonite, hydroxypropyl starch, sodium carboxymethylcellulose, sodium alginate, Disintegrants such as carboxymethylcellulose calcium, calcium citrate, sodium lauryl sulfate, anhydrous silicic acid, 1-hydroxypropyl cellulose, dextran, ion exchange resin, polyvinyl acetate, formaldehyde-treated casein and gelatin, alginic acid, amylose, guar gum, baking soda, polyvinylpyrrolidone, calcium phosphate, gelled starch, gum arabic, amylopectin, pectin, sodium polyphosphate, ethylcellulose, sucrose, magnesium aluminum silicate, di-sorbitol solution, and light anhydrous silicic acid;Lubricants such as calcium stearate, magnesium stearate, stearic acid, hydrogenated vegetable oil, talc, lycopodium dentata, kaolin, petrolatum, sodium stearate, cacao butter, sodium salicylate, magnesium salicylate, polyethylene glycol (PEG) 4000, PEG 6000, liquid paraffin, hydrogenated soybean oil (Lubri wax), aluminum stearate, zinc stearate, sodium lauryl sulfate, magnesium oxide, macrogol, synthetic aluminum silicate, anhydrous silicic acid, higher fatty acids, higher alcohols, silicone oil, paraffin oil, polyethylene glycol fatty acid ether, starch, sodium chloride, sodium acetate, sodium oleate, dl-leucine, and light anhydrous silicic acid can be used.

[0077] As additives of the liquid formulation according to the present invention, water, dilute hydrochloric acid, dilute sulfuric acid, sodium citrate, monostearate sucrose, polyoxyethylene sorbitol fatty acid esters (twin esters), polyoxyethylene monoalkyl ethers, lanolin ethers, lanolin esters, acetic acid, hydrochloric acid, ammonia water, ammonium carbonate, potassium hydroxide, sodium hydroxide, prolamine, polyvinylpyrrolidone, ethylcellulose, sodium carboxymethylcellulose, etc. can be used.

[0078] The syrup according to the present invention may include a solution of white sugar, other sugars, or sweeteners, and may also include a fragrance, a coloring agent, a preservative, a stabilizer, a suspending agent, an emulsifier, a viscosity modifier, and the like, as needed.

[0079] Purified water may be used in the emulsion according to the present invention, and emulsifiers, preservatives, stabilizers, fragrances, etc. may be used as needed.

[0080] The suspension according to the present invention may include suspending agents such as acacia, tragacanth, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, sodium alginate, hydroxypropylmethylcellulose (HPMC), HPMC 1828, HPMC 2906, and HPMC 2910, and surfactants, preservatives, stabilizers, colorants, and fragrances may be used as needed.

[0081] The injection according to the present invention includes a solvent such as distilled water for injection, 0.9% sodium chloride injection, Ringer's injection, dextrose injection, dextrose + sodium chloride injection, PEG, lactated Ringer's injection, ethanol, propylene glycol, non-volatile oils - sesame oil, cottonseed oil, peanut oil, soybean oil, corn oil, ethyl oleate, isopropyl myristate, and benzene benzoate; a solubilizing agent such as sodium benzoate, sodium salicylate, sodium acetate, urea, urethane, monoethylacetamide, butazolidine, propylene glycol, tween, nitrile acid amide, hexamine, and dimethylacetamide; a buffer such as weak acids and their salts (acetic acid and sodium acetate), weak bases and their salts (ammonia and ammonium acetate), organic compounds, proteins, albumin, peptone, and gums; It may include isotonic agents such as sodium chloride; stabilizers such as sodium bisulfite (NaHSO3), carbon dioxide gas, sodium metabisulfite (Na2S2O5), sodium sulfite (Na2SO3), nitrogen gas (N2), and ethylenediaminetetraacetic acid; oxidizing agents such as sodium bisulfite 0.1%, sodium formaldehyde sulfoxylate, thiourea, disodium ethylenediaminetetraacetic acid, and acetone sodium bisulfite; analgesics such as benzyl alcohol, chlorobutanol, procaine hydrochloride, glucose, and calcium gluconate; and suspending agents such as sodium cis-methylenediamine, sodium alginate, Tween 80, and aluminum monostearate.

[0082] The suppository according to the present invention comprises cocoa butter, lanolin, withepsol, polyethylene glycol, glycerogelatin, methylcellulose, carboxymethylcellulose, a mixture of stearic acid and oleic acid, Subanal, cottonseed oil, peanut oil, palm oil, cocoa butter + cholesterol, lecithin, ranet wax, glycerol monostearate, Tween or Span, Imhausen, monolene (propylene glycol monostearate), glycerin, Adeps solidus, Buytyrum Tego-G, Cebes Pharma 16, hexalide base 95, Cotomar, Hydroxocote SP, S-70-XXA, S-70-XX75 (S-70-XX95), Mechanisms such as Hydrokote 25, Hydrokote 711, Idropostal, Massa estrarium (A, AS, B, C, D, E, I, T), Massa-MF, Masupol, Masupol-15, Neosupostal-N, Paramound-B, Suposiro (OSI, OSIX, A, B, C, D, H, L), Suppository type IV (AB, B, A, BC, BBG, E, BGF, C, D, 299), Supostal (N, Es), Wecovi (W, R, S, M, Fs), and Tezester triglyceride basis (TG-95, MA, 57) can be used.

[0083] Solid dosage forms for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid dosage forms are prepared by mixing the extract with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

[0084] Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups. In addition to commonly used simple diluents such as water and liquid paraffin, they may contain various excipients such as wetting agents, sweeteners, flavoring agents, and preservatives. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions can include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.

[0085] The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment / prevention. The effective dosage level may be determined based on factors including the type and severity of the patient's disease, drug activity, drug sensitivity, administration time, administration route and excretion rate, treatment / administration period, concurrently used drugs, and other factors well known in the medical field.

[0086] The pharmaceutical composition according to the present invention can be administered as an individual therapeutic / preventive agent or in combination with other therapeutic / preventive agents. It can be administered sequentially or simultaneously with conventional therapeutic / preventive agents, and can be administered singly or in multiple doses. Taking all of the above factors into account, it is important to administer an amount that achieves maximum efficacy with the minimum amount possible without causing side effects. This can be readily determined by those skilled in the art to which the present invention pertains.

[0087] The pharmaceutical composition of the present invention can be administered to a subject via various routes. All modes of administration are conceivable, including oral ingestion, subcutaneous injection, intraperitoneal administration, intravenous injection, intramuscular injection, intrathecal injection, sublingual administration, buccal mucosal administration, rectal insertion, vaginal insertion, ocular administration, otic administration, nasal administration, inhalation, oral or nasal spraying, dermal administration, and transdermal administration.

[0088] The pharmaceutical composition of the present invention is determined according to the type of drug as an active ingredient, along with various related factors such as the disease to be treated / prevented, the route of administration, the patient's age, sex, weight, and the severity of the disease. Specifically, the effective dose of the composition according to the present invention may vary depending on the patient's age, sex, and weight, and is generally 0.001 to 150 mg per 1 kg of body weight, preferably 0.01 to 100 mg, administered daily or every other day, or divided into 1 to 3 times a day. However, since the dosage may increase or decrease depending on the route of administration, the severity of the disease, sex, weight, age, etc., the above dosage does not limit the scope of the present invention in any way.

[0089] In the present invention, “subject” means a subject requiring treatment / prevention of a disease, and more specifically, means a mammal such as a human or non-human primate, mouse, rat, dog, cat, horse, and cow.

[0090] In the present invention, “administration” means providing a predetermined composition of the present invention to an individual by any appropriate method.

[0091] In the present invention, “prevention” means any action that suppresses or delays the onset of a target disease, and “treatment” means any action that improves or beneficially changes the target disease and its accompanying metabolic abnormality symptoms by administering a pharmaceutical composition according to the present invention.

[0092] In addition, the present invention provides a method for preventing cancer, comprising administering to a subject in need thereof a pharmaceutically effective amount of a composition comprising / consisting of at least one selected from the group consisting of thymocytes and thymic epithelial cells; or at least one selected from the group consisting of thymocytes and thymic epithelial cells as an active ingredient.

[0093] In addition, the present invention provides a use for cancer prevention of a composition comprising / consisting of at least one selected from the group consisting of thymocytes and thymic epithelial cells; or at least one selected from the group consisting of thymocytes and thymic epithelial cells; as an active ingredient.

[0094] In addition, the present invention provides a use for manufacturing a cancer prevention agent comprising a composition comprising / consisting of at least one selected from the group consisting of thymocytes and thymic epithelial cells; or at least one selected from the group consisting of thymocytes and thymic epithelial cells as an active ingredient.

[0095] The present invention provides a cancer prevention kit comprising a composition comprising at least one selected from the group consisting of thymocytes and thymic epithelial cells, and an instruction manual.

[0096] In the present invention, the term "kit" refers to a tool that enables the prevention (or treatment) of cancer by autologous transplantation of thymocytes or thymic epithelial cells of the present invention. In addition to the above-mentioned substances, the kit of the present invention may include other components, compositions, solutions, devices, etc. that are typically required for the storage and processing methods thereof. As a specific example, each component may be applied at least once without limitation in the number of times, there is no restriction on the order in which each substance is applied, and the application of each substance may be performed simultaneously or microscopically.

[0097] In the present invention, the kit may include a container; instructions; and the like. The container may serve to package the substance, and may also serve to store and fix the substance. The material of the container may take the form of, for example, a bottle, a tub, a sachet, an envelope, a tube, an ampoule, and the like, and these may be formed partially or wholly from plastic, glass, paper, foil, wax, and the like. The container may be initially equipped with a completely or partially detachable stopper, which may be part of the container or may be attached to the container by mechanical, adhesive, or other means, and may also be equipped with a stopper for allowing access to the contents by means of a syringe needle. The kit may include an outer package, and the outer package may include instructions for the use of the components.

[0098]

[0099] Hereinafter, preferred examples are presented to aid in understanding the present invention. However, the following examples are provided solely to facilitate a better understanding of the present invention, and the scope of the present invention is not limited by the following examples.

[0100]

[0101] [Example]

[0102] Example 1. Extraction of thymocytes or thymic epithelial cells and production of a DMBA-induced cancer mouse model.

[0103] To confirm the cancer prevention effect of thymocytes or thymic epithelial cells of the present invention, a cancer mouse model was created. Specifically (Fig. 1), thymocytes or thymic epithelial cells were extracted from the thymus of a fluorescently labeled 5-day-old juvenile mouse, c57bl / 6j, and then transplanted into the same mouse when it became an old mouse at 40 weeks of age. Three weeks after the thymocyte or thymic epithelial cell transplantation, DMBA (7,12-Dimethylbenz[a]anthracene) was applied to the skin to induce skin cancer. In addition, TPA (12-O-tetradecanoylphorbol-13-acetate) was treated twice a week from the 4th to the 21st week based on the thymocyte or thymic epithelial cell transplantation to accelerate the rate of cancer induction. Blood samples were sampled every three weeks from week 3 to week 21 after thymocyte or thymic epithelial cell transplantation.

[0104]

[0105] Example 2. Observation of mice after transplantation of thymocytes or thymic epithelial cells.

[0106] Fluorescently labeled thymocytes or thymic epithelial cells from 5-day-old juvenile mice were injected into the thymus of a 40-week-old mouse in the DMBA-induced cancer mouse model produced in Example 1, and then observed for 7 days (Fig. 2a).

[0107] As a result, it was confirmed that thymocytes or thymic epithelial cells of juvenile mice migrated and located in the thymus of old mice (Fig. 2b).

[0108]

[0109] Example 3. Confirmation of anticancer effect by transplantation of thymocytes or thymic epithelial cells.

[0110] Example 3-1. Morphological analysis of mice

[0111] To confirm the cancer prevention effect of thymocyte or thymic epithelial cell transplantation, morphological analysis was performed on skin cancer-induced mice transplanted with each cell.

[0112] As a result (Fig. 3a), in mice where the cell transplantation was not performed, cancer development was observed in 3 out of 4 mice, resulting in a 75% probability of cancer being observed in the mice, while no cancer development was observed in mice where thymocytes and thymic epithelial cells were transplanted.

[0113] Example 3-2. H&E staining analysis

[0114] To confirm the cancer prevention effect of thymocyte or thymic epithelial cell transplantation, H&E staining was performed on skin cancer-induced mice transplanted with each cell.

[0115] As a result (Figs. 3b and 3c), skin cancer did not develop in mice transplanted with thymocytes or thymic epithelial cells, and the epidermis was confirmed to be thinner than in mice that were not transplanted with the cells. According to this, the degree of hyperplastic epidermis and immune inflammatory cell infiltration accompanying cancer induction was significantly suppressed by transplantation of thymocytes or thymic epithelial cells, and in particular, this effect was statistically significant, suggesting that cancer can be effectively prevented by transplantation of thymocytes or thymic epithelial cells of the present invention.

[0116]

[0117] The foregoing description of the present invention is provided for illustrative purposes only. Those skilled in the art will readily appreciate that the present invention can be readily modified into other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

[0118]

[0119] According to the pharmaceutical composition for preventing cancer comprising thymic cells or thymic epithelial cells of the present invention as an active ingredient, cancer can be prevented using thymic cells or thymic epithelial cells from childhood. Accordingly, the present invention can utilize thymic cells or thymic epithelial cells that naturally degenerate after a certain period of time, and the extracted thymic cells or thymic epithelial cells can be easily processed through autologous transplantation, making it useful as a composition for preventing cancer, and thus has industrial applicability.

Claims

1. A pharmaceutical composition for preventing cancer, comprising as an active ingredient at least one selected from the group consisting of thymocytes and thymic epithelial cells.

2. In paragraph 1, A pharmaceutical composition, characterized in that the composition is composed of thymocytes or thymic epithelial cells.

3. In paragraph 1, A pharmaceutical composition, wherein the composition is autologous.

4. In paragraph 1, The above thymic epithelial cells express keratin, MHC class Ⅱ, and CD5 + TCRβ + , CD69 + TCRβ + A pharmaceutical composition expressing at least one marker selected from the group consisting of:

5. In paragraph 1, A pharmaceutical composition, wherein the thymic epithelial cells are cortical thymic epithelial cells or medullary thymic epithelial cells.

6. In paragraph 5, A pharmaceutical composition, wherein the above cortical thymic epithelial cells express at least one marker selected from the group consisting of aminopeptidase A (BP-1), C11, and CD205 (cortex specific keratin subunits).

7. In paragraph 5, A pharmaceutical composition, wherein the above-mentioned thymic epithelial cells express at least one marker selected from the group consisting of Ep-CAM, K5, and UEA-1.

8. In paragraph 1, A pharmaceutical composition, wherein the cancer is at least one selected from the group consisting of skin cancer, breast cancer, colon cancer, stomach cancer, oral cancer, lung cancer, cervical cancer, uterine cancer, endometrial cancer, vaginal cancer, tonsil cancer, pharyngeal cancer, laryngeal cancer, brain tumor, liver cancer, pancreatic cancer, leukemia, esophageal cancer, prostate cancer, bladder cancer, ovarian cancer, pituitary adenoma, small intestine cancer, rectal cancer, colon cancer, thyroid cancer, lymphoma, and renal cell carcinoma.

9. In paragraph 1, A pharmaceutical composition characterized in that the composition comprises at least one selected from the group consisting of: a) Inhibition of epidermal thickness increase due to skin cancer; b) reduction in the number of inflammatory cells; and c) Immune system strengthening effect.

10. A kit for preventing cancer, comprising a composition comprising at least one selected from the group consisting of thymocytes and thymic epithelial cells, and an instruction manual.

11. A method for preventing cancer, comprising the step of administering to a subject in need thereof a pharmaceutically effective amount of a composition comprising / consisting of at least one active ingredient selected from the group consisting of thymocytes and thymic epithelial cells; or at least one active ingredient selected from the group consisting of thymocytes and thymic epithelial cells.

12. Use of a composition comprising / consisting of at least one selected from the group consisting of thymocytes and thymic epithelial cells; or at least one selected from the group consisting of thymocytes and thymic epithelial cells as an effective ingredient; for use in preventing cancer.

13. A use for producing a cancer prevention agent comprising at least one selected from the group consisting of thymocytes and thymic epithelial cells; or a composition comprising / consisting of at least one selected from the group consisting of thymocytes and thymic epithelial cells as an active ingredient.

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