WO2021162419A1 - Composition destinée à prévenir ou à traiter le cancer au moyen d'une induction de maturation de cellules dendritiques immatures - Google Patents

Composition destinée à prévenir ou à traiter le cancer au moyen d'une induction de maturation de cellules dendritiques immatures Download PDF

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WO2021162419A1
WO2021162419A1 PCT/KR2021/001721 KR2021001721W WO2021162419A1 WO 2021162419 A1 WO2021162419 A1 WO 2021162419A1 KR 2021001721 W KR2021001721 W KR 2021001721W WO 2021162419 A1 WO2021162419 A1 WO 2021162419A1
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cancer
dendritic cells
composition
strain
mature dendritic
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PCT/KR2021/001721
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English (en)
Korean (ko)
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진화섭
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주식회사 리스큐어바이오사이언시스
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Priority claimed from KR1020210017768A external-priority patent/KR20210102090A/ko
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Publication of WO2021162419A1 publication Critical patent/WO2021162419A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/464499—Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/20—Animal feeding-stuffs from material of animal origin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A61K39/4615—Dendritic cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
    • A61K39/4622—Antigen presenting cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
    • A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
    • A61K2239/50—Colon

Definitions

  • the present invention relates to a composition for preventing or treating cancer using the induction of maturation of immature dendritic cells. Specifically, the T lymphocyte immune response to cancer cells by maturation of immature dendritic cells using a Lactobacillus sakei strain. It relates to a composition for preventing or treating cancer that can induce
  • Cancer has the highest mortality rate worldwide and is the second most common cause of death in Western societies after cardiovascular disease.
  • the consumption of high-fat diets has become common due to the westernization of diets, and the incidence of colorectal cancer, breast cancer, and prostate cancer continues to increase due to the rapid increase in environmental pollutants and the increase in alcohol consumption.
  • Lung cancer is increasing due to the increase in the number of cancer cells and air pollution.
  • there is an urgent need to develop an anti-cancer therapy that can contribute to the promotion of human health, the improvement of the quality of healthy life, and the promotion of human health by enabling the early prevention and treatment of cancer.
  • Dendritic cells were found to be very important cells capable of inducing anti-tumor immunity as known by Steinman et al. as the cell with the function to induce the most effective immune response by T lymphocytes in 1975. Dendritic cells acquire antigens through phagocytosis, etc., process them inside the cells, and express them by loading antigen peptides in the major histocompatibility complex (MHC), thereby strongly inducing activation of T lymphocytes with antigen-specific T cell receptors.
  • MHC major histocompatibility complex
  • dendritic cells when activated, they express IL-12 to prevent apoptosis of T lymphocytes, induce T lymphocyte differentiation and CTL activity, as well as increase the activity of natural killer cells to enhance anti-tumor immunity. have.
  • the existing cancer treatment regimen using dendritic cells was based on a method of activating T lymphocytes by loading tumor antigens on dendritic cells and injecting them back into the human body.
  • this method has the advantage of fewer side effects compared to other anticancer drugs, but there are limitations in that it is difficult to obtain tumor antigens from the patient and activation of dendritic cells is not good.
  • Korean Patent Application Laid-Open No. 10-2019-0017705 discloses a method for activating T cells using dendritic cells, but there is no disclosure about a composition for treating cancer using dendritic cells activated using a microbial strain. .
  • An object of the present invention is to provide a composition comprising mature dendritic cells as an active ingredient, wherein the mature dendritic cells are matured using a microbial strain to prevent, improve or treat cancer.
  • Another object of the present invention is to provide a method for maturing immature dendritic cells using a microbial strain.
  • mature dendritic cells were obtained using microbial strains from immature dendritic cells differentiated from bone marrow cells, and whether the differentiated dendritic cells were activated through a composition containing them as an active ingredient and the preventive or therapeutic effect on various carcinomas was confirmed. did.
  • composition comprising mature dendritic cells using a microorganism according to the present invention as an active ingredient exhibits excellent anticancer activity in an animal model, so it can be usefully used as a composition for the treatment, prevention or improvement of cancer in humans or animals. have.
  • FIG. 1 is a diagram showing a comparison graph by measuring the DC activity marker (CD80) after treating the Lactobacillus sakeai strain in immature dendritic cells according to an embodiment of the present invention.
  • FIG. 2 is a diagram showing a comparison graph by measuring the DC activity marker (CD86) after treating the Lactobacillus sakeai strain in immature dendritic cells according to an embodiment of the present invention.
  • FIG. 3 is a diagram showing a graph comparing immature dendritic cells according to an embodiment of the present invention by measuring DC activity marker (CD40) after treating the Lactobacillus sakeai strain.
  • CD40 DC activity marker
  • FIG. 4 is a diagram showing a comparison graph by measuring the expression level of cytokine (IL-12 p40) after treating the Lactobacillus sakeai strain in immature dendritic cells according to an embodiment of the present invention.
  • cytokine IL-12 p40
  • FIG. 5 is a diagram showing a comparison graph by measuring the expression level of cytokine (Tnf- ⁇ ) after treating the Lactobacillus sakeai strain in immature dendritic cells according to an embodiment of the present invention.
  • FIG. 6 is a diagram showing a comparison graph by measuring the expression level of cytokine (Ifn- ⁇ ) after treating the Lactobacillus sakeai strain in immature dendritic cells according to an embodiment of the present invention.
  • FIG. 7 is a diagram illustrating a graph comparing immature dendritic cells according to an embodiment of the present invention by measuring the degree of proliferation (proliferation) of T cells after treating the Lactobacillus sakeai strain.
  • FIG. 8 is a diagram showing a graph comparing immature dendritic cells according to an embodiment of the present invention by measuring and comparing the secretion amount of a cytotoxic substance (perforin) according to the activity of T cells after the Lactobacillus sakeai strain was treated.
  • a cytotoxic substance perforin
  • FIG. 9 is a diagram showing a comparison graph by measuring the secretion amount of Ifn- ⁇ according to the activity of T cells after treating the Lactobacillus sakeai strain in immature dendritic cells according to an embodiment of the present invention.
  • FIG. 10 is a diagram showing a graph comparing immature dendritic cells according to an embodiment of the present invention by measuring and comparing the secretion amount of granzyme B according to the activity of T cells after the Lactobacillus sakeai strain was treated.
  • FIG. 11 is a diagram illustrating a graph measuring the volume change of tumor cells for 20 days after intraperitoneal injection of a composition according to an embodiment of the present invention into MC38 cell-transplanted mice.
  • composition comprising mature dendritic cells of the present invention as an active ingredient has a preventive or therapeutic effect on cancer and can be used as a pharmaceutical composition.
  • the mature dendritic cells are characterized in that they are matured using a microbial strain.
  • the dendritic cell (DC) of the present invention is the most essential antigen-presenting cell of the immune system capable of inducing both an innate immune response and an adaptive immune response (antigen-presenting cell, APC), which has the ability to activate naive and memory immune responses that have never been exposed to an antigen. For this reason, it is considered "Nature's adjuvant".
  • APC adaptive immune response
  • dendritic cells act as watchmen, constantly patrolling for antigens.
  • MHC class II major histocompatibility complex class II
  • CD4+ T cell activation endogenous antigen is expressed through MHC class I. present (CD8+ T cell activation).
  • dendritic cells have a special ability to cross-present exogenous antigens through MHC class II as well as MHC class I. Therefore, dendritic cells have the ability to more effectively activate CD4+ and CD8+ T cells.
  • dendritic cells After acquiring antigen, dendritic cells that have undergone maturation move to lymphoid organs and present antigens to naive T cells.
  • T cell activation requires not only antigen presentation by antigen-presenting cells, but also stimulation of costimulatory molecules (CD80, CD86, CD40, etc.) and pro-inflammatory cytokines expressed on the surface of antigen-presenting cells.
  • CD4+ T cells Through this signal, fully mature dendritic cells induce CD4+ T cells to differentiate into T helper1 (Th1) cells, and also activate CD8+ T cells (cytolytic T lymphocytes).
  • CD4+ T cells are differentiated into Th2 cells or regulatory T cells (Tregs) in the absence of stimulation of antigen-presenting cells with costimulatory factors and pro-inflammatory cytokines or when stimulated with immunosuppressive cytokines.
  • the immature dendritic cells may be differentiated by in vitro culture. Preferably, it may be differentiated from monocytes obtained from bone marrow cells into monocyte-derived dendritic cells, but is not limited thereto.
  • Immature dendritic cells differentiated through the above process can be activated into mature dendritic cells using a microbial strain.
  • the microbial strain may be one of probiotics, and 'probiotics' refers to living microorganisms that have a beneficial effect on the health of the host by improving the intestinal microbial environment of the host in the gastrointestinal tract of animals, including humans.
  • Probiotics are microorganisms with probiotic activity, and when fed to humans or animals in the form of single or complex strains, in the form of dried cells or fermentation products, it can have a beneficial effect on the intestinal flora of the host.
  • the microorganism strain may be one of Lactobacillus sp. strain, Weissella sp. strain, Bifidobacterium sp. strain, Leuconostoc strain or Lactococcus strain.
  • Lactobacillus fermentum strain (Lactobacillus fermentum), Lactobacillus sakei strain (Lactobacillus sakei), Lactobacillus gasseri strain (Lactobacillus gasseri), Lactobacillus plantarum strain (Lactobacillus plantarum), Lactobacillus Strain (Lactobacillus rhamnosus), Lactobacillus acidophilus strain (Lactobacillus acidophilus), Lactobacillus casei strain (Lactobacillus casei), Lactobacillus reuteri strain (Lactobacillus reuteri) It may be one or more strains selected from the group consisting of strains (Weissella hellenica) and leuconostoc cit
  • the Lactobacillus fermentum strain may have a nucleic acid sequence of SEQ ID NO: 1 (SEQ ID NO: 1), but is not limited thereto.
  • the Lactobacillus sakeai strain may have a nucleic acid sequence of SEQ ID NO: 2 (SEQ ID NO: 2), but is not limited thereto.
  • the Weissella civaria strain may have a nucleic acid sequence of SEQ ID NO: 3 (SEQ ID NO: 3), but is not limited thereto.
  • the cancers include bladder cancer, breast cancer, melanoma, thyroid cancer, parathyroid cancer, colorectal cancer, rectal cancer, throat cancer, laryngeal cancer, esophageal cancer, pancreatic cancer, stomach cancer, tongue cancer, skin cancer, brain tumor, uterine cancer, double gallbladder cancer, oral cancer, colon cancer, perianal cancer, liver cancer And it may be any one cancer selected from the group consisting of lung cancer, preferably colon cancer, but is not limited thereto.
  • composition may be administered orally or parenterally.
  • parenteral administration intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endothelial administration, topical administration, intranasal administration, intrapulmonary administration and rectal administration, etc. may be administered, preferably by intravenous injection. can be administered, but is not limited thereto.
  • a suitable dosage of the composition may be variously prescribed according to factors such as formulation method, administration method, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity of the patient.
  • the pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant includes an excipient, bog Release, sweetener, binder, coating agent, swelling agent, lubricant, lubricant or flavoring agent and the like can be used.
  • the pharmaceutical composition may be preferably formulated as a pharmaceutical composition by including one or more pharmaceutically acceptable carriers in addition to the active ingredients described above for administration.
  • the active ingredient may be combined with an orally, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like.
  • suitable binders, lubricants, disintegrants and color-developers may also be included in the mixture.
  • suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate. ate, sodium acetate, sodium chloride, and the like.
  • Disintegrants include, but are not limited to, starch, methylcellulose, agar, bentonite, xanthan gum, and the like.
  • acceptable pharmaceutical carriers include sterile and biocompatible, saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostats may be added as needed.
  • diluents such as an aqueous solution, suspension, emulsion, etc., pills, capsules, granules or tablets.
  • composition comprising mature dendritic cells of the present invention as an active ingredient may be used as a food composition or food additive composition for preventing or improving cancer.
  • the food composition may be in the form of a health functional food.
  • Health functional food means food manufactured and processed using raw materials or ingredients useful for the human body in accordance with the Health Functional Food Act (Article 3, No. 1), and “functionality” means Controlling nutrients for the structure and function of the human body or obtaining useful effects for health purposes such as physiological action (Article 2).
  • the food composition may additionally contain food additives, and the suitability as a "food additive" is determined according to the general rules and general test methods of the Food Additives Code approved by the Ministry of Food and Drug Safety, unless otherwise specified. and criteria.
  • Food Additives Code for example, chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as depigmentation, licorice extract, crystalline cellulose, and guar gum, L- Mixed preparations such as sodium glutamate preparation, noodle-added alkali agent, preservative agent, and tar color agent can be mentioned.
  • chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid
  • natural additives such as depigmentation, licorice extract, crystalline cellulose, and guar gum
  • L- Mixed preparations such as sodium glutamate preparation, noodle-added alkali agent, preservative agent, and tar color agent can be mentioned.
  • Foods containing the active ingredient of the present invention include bread, rice cakes, dried fruits, candies, chocolates, chewing gum, confectionery products such as jams, ice cream products, ice cream products, ice cream products such as ice cream powder milk, low-fat milk, lactose-decomposed milk, Processed milk, goat milk, fermented milk, buttermilk, concentrated milk, milk cream, butter oil, natural cheese, processed cheese, milk powder, milk products such as whey Processed meat products, processed eggs, meat products such as hamburgers Fish cakes, ham, Fish and meat products such as sausages, bacon, etc. Fish and meat products Ramen, dried noodles, raw noodles, fried noodles, luxurious dried noodles, improved soft noodles, frozen noodles, pastas, etc.
  • Beverages such as lactic acid bacteria drinks such as yogurt, mixed drinks, soy sauce, soybean paste, red pepper paste, chunjang, cheonggukjang, mixed soy sauce, vinegar, sauces, tomato ketchup, curry, seasoned foods such as dressings, margarine, shortening and pizza, but limited thereto it's not going to be
  • the composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, It may include a carbonation agent used in carbonated beverages, and the like.
  • the composition of the present invention may include fruit for the production of natural fruit juice, fruit juice beverage, and vegetable beverage. These components may be used independently or in combination.
  • the beverage composition including the active ingredient of the present invention is not particularly limited in other ingredients, and may contain various flavoring agents or natural carbohydrates as additional ingredients like a conventional beverage.
  • natural carbohydrates include monosaccharides (eg, glucose, fructose, etc.); disaccharides, (eg maltose, sucrose, etc.); and conventional sugars such as polysaccharides (eg, dextrin, cyclodextrin, etc.), and sugar alcohols such as xylitol, sorbitol, erythritol.
  • natural flavoring agents taumatine, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)
  • synthetic flavoring agents sacharin, aspartame, etc.
  • composition comprising the mature dendritic cells of the present invention as an active ingredient may be used as a feed composition or feed additive composition for preventing or improving cancer in livestock.
  • the composition When the composition is prepared as a feed additive, the composition may be 20 to 90% highly concentrated or may be prepared in powder or granular form.
  • the feed additives include organic acids such as citric acid, humic acid, adipic acid, lactic acid, and malic acid, or phosphates such as sodium phosphate, potassium phosphate, acid pyrophosphate, polyphosphate (polyphosphate), polyphenol, catechin, alpha-tocopherol, rosemary Extract, vitamin C, green tea extract, licorice extract, chitosan, tannic acid, any one or more of natural antioxidants such as phytic acid may be further included.
  • the composition When prepared as a feed, the composition may be formulated in the form of a conventional feed, and may include common feed ingredients together.
  • the feed and feed additives include grains such as milled or crushed wheat, oats, barley, corn and rice; plant protein feeds, such as feeds based on rape, soybean, and sunflower; animal protein feeds such as blood meal, meat meal, bone meal and fish meal; Sugar and dairy products, for example, may further include dry ingredients made of various powdered milk and whey powder, and may further include nutritional supplements, digestion and absorption enhancers, growth promoters, and the like.
  • the feed additive may be administered to the animal alone or in combination with other feed additives in an edible carrier.
  • the feed additive can be easily administered to the animal as a top dressing, directly mixing them with animal feed, or as an oral formulation separate from the feed.
  • a pharmaceutically acceptable edible carrier as well known in the art to prepare an immediate release or sustained release formulation.
  • Such edible carriers may be solid or liquid, for example cornstarch, lactose, sucrose, soy flakes, peanut oil, olive oil, sesame oil and propylene glycol.
  • the feed additive may be a tablet, capsule, powder, troche or sugar-containing tablet or top dressing in microdispersed form.
  • the feed additive may be in the form of a gelatin soft capsule, or a syrup or suspension, emulsion, or solution.
  • the feed and feed additives may contain adjuvants, for example, preservatives, stabilizers, wetting or emulsifying agents, solution accelerators, and the like.
  • the feed additive may be used by being added to animal feed by immersion, spraying, or mixing.
  • the feed or feed additive of the present invention can be applied to a number of animal diets including mammals, poultry and fish.
  • Pigs, cows, horses, sheep, rabbits, goats, rodents and experimental rodents as the mammals, as well as rats, hamsters, and guinea pigs, can be used for pets (eg, dogs, cats), etc., and chickens as the poultry, It can also be used for turkey, duck, geese, pheasant, and quail, and can be used as the fish, such as carp, crucian carp and trout, but is not limited thereto.
  • Lactobacillus Permentum (Lactobacillus fermentum ) preparation of strains
  • Lactobacillus permentum strain 0.1% of the received Lactobacillus permentum strain was inoculated into 30 ml of MRS liquid medium and cultured at 37° C. for 18 hours. After incubation, centrifugation was performed at 3500 rpm for 10 minutes, and the cells were washed three times with PBS solution and then the remaining medium components were removed.
  • Lactobacillus Sakei strain 0.1% of the received Lactobacillus Sakei strain was inoculated into 30 ml of MRS liquid medium and cultured at 37° C. for 18 hours. After incubation, centrifugation was performed at 3500 rpm for 10 minutes, and the cells were washed three times with PBS solution and then the remaining medium components were removed.
  • Monocytes were isolated from the bone marrow cells of the mouse femur and tibia by centrifugation using the Ficoll gradient method.
  • the isolated monocytes were prepared in a 6-well plate at a concentration of 2 x 10 6 /well, GM-CSF 20 ng/ml, IL-4 in a culture medium (RPMI) containing Fetal Bovine Serum (FBS) 10 ng/ml were co-treated. After that, it was cultured for 6 days, and when 3 days had elapsed, it was replaced with a fresh medium and cytokines to obtain differentiated immature dendritic cells.
  • RPMI culture medium
  • FBS Fetal Bovine Serum
  • the immature dendritic cells (Immature DC) obtained in Example 2 were co-cultured with a microbial strain as a secondary stimulus for differentiation into mature dendritic cells (mature DC).
  • each immature dendritic cell was treated with the Lactobacillus sakeai strain, which is the microbial strain prepared in Example 1-2, under the conditions of Examples 3-1 to 3-3 below.
  • the prepared microbial strains were treated with immature dendritic cells at 1 MOI for 24 hours, respectively.
  • Immature dendritic cells were treated with a tumor antigen and a prepared microbial strain, respectively, at an MOI of 1, and cultured for 24 hours.
  • T cell activity was measured in vitro.
  • the mouse spleen was single-celled, and then CD3+ T cells were isolated by MACS.
  • the isolated CD3+ T cells were seeded 1x10 6 /well each in a 96-well round bottom plate and co-cultured with mature dendritic cells for 3 days. After co-culture, the degree of activation and proliferation of T cells was measured using flow cytometry and CCK8 assay, respectively.
  • 1x10 5 of the MC38 colorectal cancer cell line was injected into the mouse subcutaneously and transplanted, and then, when the size of the tumor cells reached 70-100 mm 3 , PBS (control), dendritic matured by each strain Cells and antigen-loaded dendritic cells were administered twice a week by intraperitoneal injection, respectively.
  • the results confirmed by measuring the size and volume of the tumor when 20 days have elapsed after administration are shown in FIG. 11 .
  • the composition obtained by treating microbial strains and maturing dendritic cells was administered, the anticancer effect was excellent, and thus it was possible to use the composition as a composition for prevention, improvement and treatment of cancer.

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Abstract

La présente invention concerne une composition destinée à prévenir ou à traiter le cancer au moyen d'une induction de maturation de cellules dendritiques immatures, et en particulier une composition destinée à prévenir ou à traiter le cancer au moyen d'une souche de Lactobacillus sakei faisant mûrir des cellules dendritiques immatures, afin d'induire ainsi une réponse immunitaire des lymphocytes T contre les cellules cancéreuses. La composition, qui comprend en tant que principe actif, des cellules dendritiques mûries à l'aide d'un micro-organisme selon la présente invention, présente une excellente activité anticancéreuse dans un modèle animal, et peut ainsi être utilisée efficacement en tant que composition pour le traitement, la prévention ou le soulagement du cancer chez l'être humain ou l'animal.
PCT/KR2021/001721 2020-02-11 2021-02-09 Composition destinée à prévenir ou à traiter le cancer au moyen d'une induction de maturation de cellules dendritiques immatures WO2021162419A1 (fr)

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KR10-2020-0016102 2020-02-11
KR20200016102 2020-02-11
KR1020210017768A KR20210102090A (ko) 2020-02-11 2021-02-08 미성숙 수지상 세포의 성숙화 유도를 이용한 암의 예방 또는 치료용 조성물
KR10-2021-0017768 2021-02-08

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