WO2022203303A1 - 락토바실러스 플란타럼 gb104 균주 및 이를 포함하는 암 예방 또는 치료용 조성물 - Google Patents
락토바실러스 플란타럼 gb104 균주 및 이를 포함하는 암 예방 또는 치료용 조성물 Download PDFInfo
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- cancer
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- plantarum
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
- A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
- A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
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- 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
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates to a Lactobacillus Plantarum GB104 strain (Accession No.: KCTC 14107BP) and a composition for preventing or treating cancer comprising the same as an active ingredient.
- colorectal cancer is the fourth most common malignancy in the world and the third leading cause of cancer death. Looking at the statistics on the incidence of colorectal cancer in Korea, it was not a common disease before the 1970s, but in modern times, the incidence of colorectal cancer is gradually increasing due to the westernization of diet.
- surgery is the most effective treatment method for colorectal cancer, like other gastrointestinal cancers, and the survival rate from the first stage to the third stage is 70-90%, but in the last stage, the survival rate decreases sharply to 15%.
- lactic acid bacteria are widely distributed in the oral cavity, intestine, vagina, feces, and fermented foods such as kimchi of humans and animals, and are closely related to the health of humans and animals. Lactobacillus has various health-promoting effects such as bowel action, suppression of harmful bacteria, immune regulation, lowering blood cholesterol, and anti-cancer.
- Korean Patent Publication No. 10-2015-0068061 discloses the anticancer activity of Lactobacillus plantarum PNU (KCCM11352P) or Lactobacillus mesenteroides PNU (KCCM11353P), and a Korean registered patent No. 10-1287120 discloses a pharmaceutical composition for the treatment of cancer containing Lactobacillus plantarum DSR CK10 (Accession No.: KFCC-11433P) or Lactobacillus plantarum DSR M2 (Accession No.: KFCC-11432P) as an active ingredient
- the effect has not reached the level enough to be commercially successful.
- the present inventors completed the present invention by confirming that the Lactobacillus plantarum GB104 strain (Accession No.: KCTC 14107BP) exhibits excellent anticancer effect as a result of research to develop a new strain with excellent anticancer effect.
- Lactobacillus plantarum GB104 L. Plantarum GB104
- KCTC 14107BP KCTC 14107BP
- a cancer prevention or treatment pharmaceutical comprising a culture thereof as an active ingredient A composition
- Another aspect of the present invention provides a food composition for preventing or inhibiting cancer comprising the Lactobacillus plantarum GB104 ( L. Plantarum GB104) strain (Accession No.: KCTC 14107BP) or a culture thereof as an active ingredient.
- Lactobacillus plantarum GB104 L. Plantarum GB104
- KCTC 14107BP KCTC 14107BP
- Another aspect of the present invention provides a feed composition for preventing or inhibiting cancer comprising the Lactobacillus plantarum GB104 ( L. Plantarum GB104) strain (Accession No.: KCTC 14107BP) or a culture thereof as an active ingredient.
- Lactobacillus plantarum GB104 L. Plantarum GB104
- KCTC 14107BP KCTC 14107BP
- Lactobacillus plantarum GB104 L. Plantarum GB104 strain (Accession No.: KCTC 14107BP) or a culture thereof to an individual other than a human cancer prevention or treatment method comprising the step of administering to provide.
- the Lactobacillus plantarum GB104 strain (Accession No.: KCTC 14107BP) according to the present invention increases the production of INF- ⁇ and granzyme B against a cancer cell line or a cancer cell line transplanted mouse model, and increases the production of cytotoxic T cells and NK cells. By activating immune cells, it ultimately exhibits an effect of inhibiting tumor formation and tumor growth. Therefore, the composition comprising the Lactobacillus plantarum GB104 strain of the present invention as an active ingredient can be usefully used for the prevention, improvement or treatment of cancer diseases.
- (-) is a strain untreated group as a negative control group.
- Figure 2 is after treatment of L. Plantarum GB104 strain or general lactic acid bacteria 1 ( L. Fermentum GB102) in each of the human colon cancer cell lines HCT116 and HT-29 It is a graph showing the colony-forming ability as a percentage (%) relative to the negative control group. ** P ⁇ 0.01
- HCT116 and HT-29 are human colon cancer cell lines HCT116 and HT-29, respectively, after treatment with a culture solution of L. Plantarum GB104 strain or general lactic acid bacteria 1 ( L. Fermentum GB102) It is a view confirming the colony forming ability.
- Figure 4 is after processing the culture solution of L. Plantarum GB104 strain or general lactic acid bacteria 1 ( L. Fermentum GB102) in each of the human colon cancer cell lines HCT116 and HT-29 It is a graph showing the colony-forming ability as a percentage (%) relative to the negative control group. ** P ⁇ 0.01; *** P ⁇ 0.001
- FIG. 5 is a mouse-derived colorectal carcinoma CT-26 animal model of general lactic acid bacteria 1 ( L. Fermentum GB102), general lactic acid bacteria 2 ( L. Fermentum GB103) or L. Plantarum GB104 showing an experimental schedule for confirming the cancer prevention effect It is a drawing.
- FIG. 7 is a graph showing the measurement of tumor size growth of individual experimental animals of a negative control group and a L. Plantarum GB104 strain treated group in a mouse-derived colorectal carcinoma CT-26 animal model.
- FIG. 8 is a view showing an experimental schedule for confirming the anticancer activity of the common lactic acid bacteria 3 ( L. Helveticus MG585) or L. Plantarum GB104 strain in the mouse-derived colorectal carcinoma CT-26 animal model.
- the common lactic acid bacteria 3 L. Helveticus MG585
- L. Plantarum GB104 strain in the mouse-derived colorectal carcinoma CT-26 animal model.
- FIG. 9 is a graph showing the measurement of the growth degree of tumor size after administration of L. Helveticus MG585 ( L. Helveticus MG585) and L. Plantarum GB104 strains to mouse-derived colorectal carcinoma CT-26 animal model, respectively. ** P ⁇ 0.01
- FIG. 10 is a graph showing the measurement of tumor size growth of individual experimental animals of a negative control group and a L. Plantarum GB104 strain treated group in a mouse-derived colorectal carcinoma CT-26 animal model.
- FIG. 11 is a graph showing the measurement of tumor weight after treatment with L. Plantarum GB104 strain in a mouse-derived colorectal carcinoma CT-26 animal model (left) and a photograph showing the tumor size compared with a negative control group (right). * P ⁇ 0.05
- FIG. 12 is a view showing an experimental schedule for confirming the anticancer activity of the L. Plantarum GB104 strain in the mouse-derived colorectal carcinoma MC-38 animal model.
- FIG. 13 is a graph showing the growth degree of the tumor size after administration of the L. Plantarum GB104 strain to the mouse-derived colorectal carcinoma MC-38 animal model. ** P ⁇ 0.01
- FIG. 14 is a graph showing the measurement of tumor weight after treatment with L. Plantarum GB104 strain in a mouse-derived colorectal carcinoma MC-38 animal model. * P ⁇ 0.05
- 15 is a graph showing the measurement of tumor size growth of individual experimental animals of a negative control group and a L. Plantarum GB104 strain treated group in a mouse-derived colorectal carcinoma MC-38 animal model.
- 16 is a view showing an experimental schedule for confirming changes in immune cells in the initial tumor tissue and peripheral blood after administration of the L. Plantarum GB104 strain to the mouse-derived colorectal carcinoma MC-38 animal model.
- 17 is a graph showing the results of analyzing the changes in immune cells in the initial tumor tissue after administration of the L. Plantarum GB104 strain to the mouse-derived colorectal carcinoma MC-38 animal model. * P ⁇ 0.05; **** P ⁇ 0.0001
- FIG. 19 is a view showing an experimental schedule for confirming changes in immune cells in late tumor tissues after administration of L. Plantarum GBCC_f0057 and L. Plantarum GB104 strains to mouse-derived colorectal carcinoma MC-38 animal model, respectively. .
- FIG. 20 is a graph showing the measurement of the growth degree of tumor size after administration of each of L. Plantarum GBCC_f0057 and L. Plantarum GB104 strains to a mouse-derived colorectal carcinoma MC-38 animal model. * P ⁇ 0.05
- 21 is a graph showing the measurement of tumor size growth of individual experimental animals of a negative control group and a L. Plantarum GB104 strain treated group in a mouse-derived colorectal carcinoma MC-38 animal model.
- FIG. 22 is a graph showing the results of analyzing changes in immune cells in late tumor tissues after administration of L. Plantarum GBCC_f0057 and L. Plantarum GB104 strains to mouse-derived colorectal carcinoma MC-38 animal model, respectively. * P ⁇ 0.05; ** P ⁇ 0.01
- One aspect of the present invention provides a pharmaceutical composition for preventing or treating cancer comprising the Lactobacillus plantarum GB104 ( L. Plantarum GB104) strain (Accession No.: KCTC 14107BP) or a culture thereof as an active ingredient.
- Lactobacillus plantarum GB104 L. Plantarum GB104
- KCTC 14107BP KCTC 14107BP
- Lactobacillus is a microorganism of the genus Gram-positive bacilli of aerobic or facultative anaerobes widely distributed in nature, and microorganisms belonging to the genus Lactobacillus include Lactobacillus plantarum, Sake and the like.
- Lactobacillus plantarum GB104 L. Plantarum GB104
- the strain was deposited with the Korea Research Institute of Bioscience and Biotechnology Biological Resources Center as of January 14, 2020, with deposit number KCTC 14107BP, and applied for a new strain patent in application number KR10-2020-0186738.
- the strain corresponds to a probiotic strain, is harmless to the human body, and can be used without side effects.
- L. plantarum GB104 may be used in combination with L. plantarum GB104, Lactobacillus plantarum GB104 or Lactobacillus plantarum GB104 strain (Accession No.: KCTC 14107BP).
- the L. plantarum GB104 strain (Accession No.: KCTC 14107BP) is the same as described above.
- the strain may be a live cell, a dead cell, or a cytoplasmic fraction obtained by disrupting the strain, preferably a live cell.
- the term "culture” refers to a product obtained by culturing a probiotic strain in a known medium, and the product may or may not contain the strain itself.
- the medium may be selected from known liquid medium or solid medium.
- it may be MRS liquid medium, GAM liquid medium, MRS agar medium, GAM agar medium, BL agar medium, but is not limited thereto.
- the active ingredient L. plantarum GB104 strain or a culture thereof is included in a therapeutically effective amount or a nutritionally effective concentration, 10 4 to 10 16 CFU / g, preferably 10 6 to 10 12 Included in the content of CFU / g, or include a culture having an equivalent number of live cells.
- a therapeutically effective amount or a nutritionally effective concentration 10 4 to 10 16 CFU / g, preferably 10 6 to 10 12 Included in the content of CFU / g, or include a culture having an equivalent number of live cells.
- 1 ⁇ 10 6 CFU/g or more of live cells preferably 1 ⁇ 10 8 to 1 ⁇ 10 12 CFU/g of live cells, may be administered once or dividedly over several times.
- the strain of the present invention can inhibit tumor formation.
- the strain activates immune cells.
- the term “immunity” refers to a mechanism for protecting living organisms from diseases by detecting and neutralizing pathogens and tumor cells in an organism.
- the “immunostimulation” may include all of a series of therapeutic or prophylactic strategies that reinforce the body's defense mechanisms against various diseases, such as cancer and inflammation.
- the formation of tumor cell colonies was significantly reduced compared to the negative control group ( FIGS. 1 to 4 ).
- the degree of tumor formation by administering the strain from the time the mouse-derived colorectal cancer cell line was subcutaneously transplanted into the mouse it was confirmed that tumor formation was suppressed compared to the negative control ( FIGS. 5 to 7 ).
- the L as a result of administering the L.
- the pharmaceutical composition for preventing or treating cancer comprising the L. Plantarum GB104 strain of the present invention or a culture thereof as an active ingredient may increase cancer treatment and/or preventive efficacy (efficacy).
- the L. Plantarum GB104 strain and its culture are as described above.
- the cancer is not limited thereto, but colorectal cancer, stomach cancer, liver cancer, lung cancer, breast cancer, prostate cancer, ovarian cancer, pancreatic cancer, cervical cancer, thyroid cancer, laryngeal cancer, acute myeloid leukemia, brain tumor, neuroblastoma, retinoblastoma, head and neck cancer, It may be selected from the group consisting of salivary gland cancer, melanoma, bladder cancer, esophageal cancer, skin cancer, colorectal cancer and lymphoma.
- the active ingredient may be included in any amount (effective amount) depending on the use, formulation, purpose of blending, etc., as long as it can exhibit anticancer activity, typically L. Plantarum GB104 strain An effective amount will be determined within the range of 0.001% to 20.0% by weight, based on the total weight of the composition.
- effective amount refers to an amount of an active ingredient capable of inducing an anticancer effect. Such effective amounts can be determined empirically within the ordinary ability of one of ordinary skill in the art.
- treatment may be used to include both therapeutic treatment and prophylactic treatment. In this case, prevention may be used in the sense of alleviating or reducing a pathological condition or disease of an individual.
- treatment includes any form of administration or application for treating a disease in a mammal, including a human. The term also includes inhibiting or slowing the disease or its progression; restoring or repairing damaged or missing function, thereby partially or completely relieving the disease; or stimulate inefficient processes; It includes the meaning of alleviating serious diseases.
- the term "efficacy" is defined by one or more parameters, such as survival or disease-free survival over a period of time, such as 1 year, 5 years, or 10 years. can be decided.
- the parameter may include suppressing the size of at least one tumor in the subject.
- “enhanced efficacy” eg, improvement in efficacy
- a therapeutically effective amount refers to an amount of a compound or composition effective for preventing or treating a target disease, which is sufficient to treat the disease at a reasonable benefit/risk ratio applicable to medical treatment, and It means an amount that does not cause side effects.
- the level of the effective amount is determined by the patient's health status, the type of disease, the severity, drug activity, sensitivity to the drug, administration method, administration time, administration route and excretion rate, treatment period, factors including the combination or concurrently used drugs; It may be determined according to factors well known in the medical field.
- a therapeutically effective amount refers to an amount of a drug effective to treat cancer.
- the pharmaceutical composition may further include a pharmaceutically acceptable carrier in addition to the active ingredient.
- a pharmaceutically acceptable carrier may be any non-toxic material suitable for delivery to a patient. Distilled water, alcohol, fats, waxes and inert solids may be included as carriers. Pharmaceutically acceptable adjuvants (buffers, dispersants) may also be included in the pharmaceutical composition.
- cryoprotectant may be at least one selected from the group consisting of glycerol, trehalose, maltodextrin, powdered skim milk and starch.
- excipient may be one or more selected from the group consisting of glucose, dextrin, and powdered skim milk.
- the cryoprotectant may be included in an amount of 0.01 wt% to 20 wt%, 0.01 wt% to 10 wt%, based on the total weight of the composition, specifically, the glycerol is 5 wt% to 20 wt%, and the trehalose is 2 wt% to 10 wt% Weight %, the maltodextrin may be included in an amount of 2 wt% to 10 wt%, the powdered skim milk in an amount of 0.5 wt% to 2 wt%, and the starch in an amount of 0.1 wt% to 1 wt%.
- the excipient may be included in an amount of 75 wt% to 95 wt% or 85 wt% to 95 wt% based on the total weight of the composition.
- Carriers and diluents that may be included in the pharmaceutical composition include gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydro oxybenzoate, talc, magnesium stearate and mineral oil.
- it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are usually used.
- the pharmaceutical composition according to the present invention is not particularly limited in its formulation, administration route and administration method as long as the effect of the present invention is exhibited.
- the composition of the present invention can be administered to mammals including humans by any method. For example, it can be administered orally.
- composition of the present invention may be formulated as a formulation for oral administration according to the route of administration as described above.
- the composition of the present invention may be formulated as a powder, granule, tablet, pill, dragee, capsule, liquid, gel, syrup, slurry, suspension, etc. using methods known in the art. can
- the pharmaceutical composition When the pharmaceutical composition is prepared for oral use, it may further include a carrier for oral administration.
- Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like.
- Suitable stabilizers include antioxidants such as sodium hydrogen sulfite, sodium sulfite or ascorbic acid.
- Suitable preservatives include benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol.
- the pharmaceutical composition of the present invention may further include an anti-aggregating agent, a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, and the like, in addition to the above components.
- oral preparations can be obtained by mixing the active ingredient with a solid excipient, pulverizing it, adding a suitable adjuvant, and processing it into a granule mixture to obtain tablets or dragees.
- suitable excipients include sugars including lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol and maltitol, and starches, including corn starch, wheat starch, rice starch and potato starch, cellulose, Cellulose, including methylcellulose, sodium carboxymethylcellulose and hydroxypropylmethyl-cellulose, and the like, fillers such as gelatin, polyvinylpyrrolidone, and the like may be included.
- cross-linked polyvinylpyrrolidone, agar, alginic acid or sodium alginate may be added as a disintegrant if necessary.
- the pharmaceutical composition of the present invention may be administered in a pharmaceutically effective amount.
- pharmaceutically effective amount means an amount sufficient to treat or prevent a disease at a reasonable benefit/risk ratio applicable to medical treatment or prevention.
- the effective dose level depends on the severity of the disease, the activity of the drug, the patient's age, weight, health, sex, the patient's sensitivity to the drug, the time of administration of the composition of the present invention used, the route of administration and the rate of excretion, the duration of treatment, and the present invention used. It may be determined according to factors including drugs used in combination or concurrently with the composition of the drug and other factors well known in the medical field.
- a preferred dosage of the pharmaceutical composition is in the range of 0.01 ⁇ g/kg to 10 g/kg, or 0.01 mg/kg to 1 g/kg per day, depending on the patient's condition, weight, sex, age, patient's severity, and administration route.
- can be Administration may be performed once a day or divided into several times. Such dosages should not be construed as limiting the scope of the invention in any respect.
- Subjects to which the pharmaceutical composition can be applied are mammals and humans, particularly preferably humans.
- the pharmaceutical composition of the present invention may further include any compound or natural extract known to have anticancer activity and safety has already been verified for the enhancement and reinforcement of anticancer activity.
- the pharmaceutical composition of the present invention may be administered sequentially or simultaneously with the conventional therapeutic agent. and may be administered single or multiple. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects.
- Another aspect of the present invention provides a food composition for preventing or inhibiting cancer comprising the Lactobacillus plantarum GB104 ( L. Plantarum GB104) strain (Accession No.: KCTC 14107BP) or a culture thereof as an active ingredient.
- Lactobacillus plantarum GB104 L. Plantarum GB104
- KCTC 14107BP KCTC 14107BP
- the L. Plantarum GB104 strain (Accession No.: KCTC 14107BP) is the same as described above.
- the food composition for preventing or inhibiting cancer includes all forms of functional food, nutritional supplement, health food, and food additives, such as food compositions of this type It can be prepared in various forms according to conventional methods known in the art.
- the strain or culture thereof When the L. Plantarum GB104 strain or a culture thereof is used as a food additive, the strain or culture may be added as it is or used together with other foods or food ingredients.
- the mixed amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment). In general, it may be added in an amount of 0.0001% by weight to 1% by weight, specifically 0.001% by weight to 0.1% by weight of the raw material composition containing the strain in the production of food or beverage. However, in the case of long-term intake for health and hygiene purposes or health control purposes, the above amount may be used below the above range.
- Another aspect of the present invention provides a feed composition for preventing or inhibiting cancer comprising the Lactobacillus plantarum GB104 ( L. Plantarum GB104) strain (Accession No.: KCTC 14107BP) or a culture thereof as an active ingredient.
- Lactobacillus plantarum GB104 L. Plantarum GB104
- KCTC 14107BP KCTC 14107BP
- the L. Plantarum GB104 strain (Accession No.: KCTC 14107BP) is the same as described above.
- the feed composition for preventing or inhibiting cancer can be prepared by adding L. Plantarum GB104 strain (Accession No.: KCTC 14107BP) or a culture thereof in an appropriate effective concentration range according to various feed preparation methods known in the art.
- Another aspect of the present invention provides the use of a pharmaceutical composition comprising the L. Plantarum GB104 strain or a culture thereof for treating a cancer disease.
- L. Plantarum GB104 strain, cancer and treatment are the same as described above.
- Another aspect of the present invention provides the use of a pharmaceutical composition comprising the L. Plantarum GB104 strain or a culture thereof for enhancing the therapeutic effect of a cancer disease.
- L. Plantarum GB104 strain, cancer and treatment are the same as described above.
- Another aspect of the present invention provides a method of treating a cancer disease and/or improving the therapeutic effect, comprising administering the Lactobacillus plantarum GB104 strain or a culture thereof to a subject.
- L. Plantarum GB104 strain, cancer and treatment are the same as described above.
- the subject may be a subject suffering from cancer.
- the subject may be a mammal, preferably a human.
- the administration route, dosage, and frequency of administration of the L. Plantarum GB104 strain or its culture may be administered to the subject in various ways and amounts depending on the patient's condition and presence or absence of side effects, and the optimal administration method, dosage and frequency of administration may be selected within an appropriate range by those skilled in the art.
- other drugs with known therapeutic effects on cancer diseases eg, the above-mentioned anticancer drugs
- physiologically active substances may be administered in combination, or formulated in the form of a combination preparation with other drugs. .
- Example 1 L. Plantarum Confirmation of tumor formation inhibitory effect according to GB104 strain or its culture medium treatment
- human colorectal cancer cell lines HCT116 and HT-29 were each diluted in 2 mL of McCoy's 5A medium, and then aliquoted to 1.5 ⁇ 10 3 cells/well in a 6-well cell culture plate and stabilized for 24 hours. After 24 hours, the medium was removed and samples were treated with fresh medium.
- general lactic acid bacteria 1 L. Fermentum GB102
- KCTC14105BP KCTC14105BP
- L. Plantarum GB104 strain was used as a sample.
- the strain was directly treated with colorectal cancer cell lines ( FIGS. 1 and 2 ), or treated in the form of a strain culture supernatant (CFS) prepared by filtering ( FIGS. 3 and 4 ). At this time, when the strain was directly treated, it was treated at a concentration of 1 ⁇ 10 7 CFU/mL.
- CFS strain culture supernatant
- the medium was replaced with a new medium containing the strain or the strain culture supernatant every 2-3 days, and cultured for 10 days.
- the cultured plate was washed twice with DPBS and fixed by treatment with 4% formalin.
- the fixed cells were washed twice with DPBS and stained with 0.5% crystal violet solution for 5 minutes. Thereafter, the colony forming ability was confirmed by washing with distilled water.
- the cancer prevention effect of L. Plantarum GB104 strain was confirmed using the mouse-derived colorectal carcinoma CT-26 animal model.
- mice 6-week-old Balb/c mice (Orient Bio, Korea) were obtained and acclimatized for 1 week. At 7 weeks of age, after hair removal around the right flank of mice, CT-26 cells, a colorectal cancer cell line derived from Balb/c mice, were injected subcutaneously at 5 ⁇ 10 5 cells/100 ⁇ L per mouse to establish a tumor animal model.
- Tumor volume (mm 3 ) (width 2 ⁇ long axis (length))/2
- a tumor animal model was established in the same manner as in Example 2, and the formed tumor was measured. On the 5th day of tumor cell injection, only mice having a tumor size within the range of 30-50 mm 3 were selected and each group was randomly set. Common lactic acid bacteria 3 ( L. Helveticus MG585) (Accession No.: KCTC14110BP) or L. Plantarum GB104 strain was used as a sample, and 1 ⁇ 10 9 CFU/animal was orally administered daily from the 6th day until just before the end of the test in the animal model. (Fig. 8).
- mice-derived colorectal carcinoma MC-38 animal model Using the mouse-derived colorectal carcinoma MC-38 animal model, the tumor treatment effect by administration of the L. Plantarum GB104 strain was confirmed.
- C57BL/6 mice (Orient Bio, Korea) were obtained and acclimatized for one week.
- MC-38 cells a colorectal cancer cell line derived from C57BL/6 mice, were injected subcutaneously at 5 ⁇ 10 5 cells/100 ⁇ L per mouse to establish a tumor animal model.
- the tumor size was measured and calculated in the same manner as in Example 2.
- mice having a tumor size within the range of 30-50 mm 3 were selected and each group was randomly set.
- the L. Plantarum GB104 strain was orally administered daily from the 6th day to just before the end of the test at 1 ⁇ 10 9 CFU/animal to the animal model ( FIG. 12 ).
- Example 5 Immune cell changes in the initial tumor tissue and peripheral blood after administration of the GB104 strain: MC-38 model
- mice-derived colorectal carcinoma MC-38 animal model Using the mouse-derived colorectal carcinoma MC-38 animal model, the changes in the initial tumor tissue and the initial immune cells in the peripheral blood were confirmed by the administration of the L. Plantarum GB104 strain.
- the L. Plantarum GB104 strain was injected into a tumor model mouse established by subcutaneously injecting C57BL/6 mouse-derived colorectal cancer cell line MC-38 cells at 2 ⁇ 10 5 cells/100 ⁇ L per mouse. It was orally administered daily from the 7th day at 1 ⁇ 10 9 CFU/animal.
- day 13 Six days after the start of administration (day 13), tumor tissues and blood were collected from mice to isolate immune cells (FIG. 16). The isolated immune cells were stained with a fluorescent antibody binding to each immune cell marker, and then analyzed using FACSymphony equipment. Antibody information is shown in Table 1.
- Anti-CD8a-Pacific Blue Biolegend 100725 Anti-CD45-BV711 Biolegend 103147 anti-CD3-FITC Biolegend 100204 anti-NK-1.1-PE Biolegend 108708 Anti-Granzyme B-PE-Cy7 eBioscience 25-8898-82 anti-IFN- ⁇ -APC Biolegend 505810 anti-CD25-PE Biolegend 101904 anti-CD4-PE-Cy7 Biolegend 100422 Anti-Foxp3-APC eBioscience 17-5773-82 Anti-CD11b-Pacific Blue Biolegend 101224 Anti-F4/80-FITC Biolegend 123108 anti-CD206-PE Biolegend 141706 Anti-CD45-APC Biolegend 103112
- Plantarum GB104 strain administered group was significantly increased compared to the negative control group.
- the ratio of regulatory T cells (Tregs cells) known to enable tumor immunity evasion by suppressing tumor-specific immune responses and establishing an immunosuppressive tumor microenvironment was significantly reduced in the L. Plantarum GB104 strain administered group (Fig. 17).
- cytotoxic T cells CD8 + T cells
- NK cells natural killer cells
- Plantarum GB104 strain administered group ratio increased significantly.
- IFN- ⁇ secreted by these cells was also significantly increased.
- M2 macrophages which are known to help the proliferation of cancer cells, significantly decreased in the L. Plantarum GB104 strain administered group (FIG. 18).
- mice-derived colorectal carcinoma MC-38 animal model Using the mouse-derived colorectal carcinoma MC-38 animal model, the change of immune cells in the late tumor tissue by administration of the L. Plantarum GB104 strain was confirmed.
- the normal lactic acid bacteria 4 L. Plantarum GBCC_f0057; GI Biome self-isolated isolate
- L. Plantarum GB104 strain was administered to the tumor model mouse established in the same manner as in Example 5 at 1 ⁇ 10 9 CFU/animal on the 7th day It was administered orally daily. Thirteen days after administration (day 20), the test was terminated, and tumor tissues were collected from mice to isolate immune cells (FIG. 19). The isolated immune cells were stained with a fluorescent antibody in the same manner as in Example 5, and then analyzed using FACSymphony equipment. Antibodies shown in Table 1 were used.
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Abstract
Description
항체 | 제조사 | Cat. NO |
항-CD8a-Pacific Blue | Biolegend | 100725 |
항-CD45-BV711 | Biolegend | 103147 |
항-CD3-FITC | Biolegend | 100204 |
항-NK-1.1-PE | Biolegend | 108708 |
항-Granzyme B-PE-Cy7 | eBioscience | 25-8898-82 |
항-IFN-γ-APC | Biolegend | 505810 |
항-CD25-PE | Biolegend | 101904 |
항-CD4-PE-Cy7 | Biolegend | 100422 |
항-Foxp3-APC | eBioscience | 17-5773-82 |
항-CD11b-Pacific Blue | Biolegend | 101224 |
항-F4/80-FITC | Biolegend | 123108 |
항-CD206-PE | Biolegend | 141706 |
항-CD45-APC | Biolegend | 103112 |
Claims (7)
- 락토바실러스 플란타럼 GB104(L. Plantarum GB104) 균주(기탁번호: KCTC 14107BP) 또는 이의 배양물을 유효성분으로 포함하는 암 예방 또는 치료용 약학 조성물.
- 제1항에 있어서,상기 균주 또는 이의 배양물이 종양 형성 억제 효과를 나타내는 것을 특징으로 하는, 암 예방 또는 치료용 약학 조성물.
- 제1항에 있어서,상기 균주가 면역증진 효과를 나타내는 것을 특징으로 하는, 암 예방 또는 치료용 약학 조성물.
- 제1항에 있어서,상기 암은 대장암, 위암, 간암, 폐암, 유방암, 전립선암, 난소암, 췌장암, 자궁경부암, 갑상선암, 후두암, 급성 골수성 백혈병, 뇌종양, 신경모세포종, 망막모세포종, 두경부암, 침샘암, 흑색종, 방광암, 식도암, 피부암, 결장직장암 및 림프종으로 구성된 군에서 선택되는 어느 하나인 것인, 암 예방 또는 치료용 약학 조성물.
- 락토바실러스 플란타럼 GB104(L. Plantarum GB104) 균주(기탁번호: KCTC 14107BP) 또는 이의 배양물을 유효성분으로 포함하는 암 예방 또는 억제용 식품 조성물.
- 락토바실러스 플란타럼 GB104(L. Plantarum GB104) 균주(기탁번호: KCTC 14107BP) 또는 이의 배양물을 유효성분으로 포함하는 암 예방 또는 억제용 사료 조성물.
- 락토바실러스 플란타럼 GB104(L. Plantarum GB104) 균주(기탁번호: KCTC 14107BP) 또는 이의 배양물을 인간을 제외한 개체에 투여하는 단계를 포함하는 암 예방 또는 치료 방법.
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US18/550,644 US20240293484A1 (en) | 2021-03-22 | 2022-03-21 | Lactobacillus plantarum gb104 strain and composition comprising same for prevention or treatment of cancer |
EP22776005.5A EP4316499A4 (en) | 2021-03-22 | 2022-03-21 | LACTOBACILLUS PLANTARUM GB104 STRAIN AND COMPOSITION COMPRISING SAME FOR THE PREVENTION OR TREATMENT OF CANCER |
CN202280019662.6A CN117042786A (zh) | 2021-03-22 | 2022-03-21 | 植物乳杆菌gb104菌株及包含其的用于预防或治疗癌症的组合物 |
JP2023549033A JP2024511269A (ja) | 2021-03-22 | 2022-03-21 | ラクトバチルス・プランタルムgb104株及びそれを含むがんの予防又は処置のための組成物 |
AU2022243439A AU2022243439A1 (en) | 2021-03-22 | 2022-03-21 | Lactobacillus plantarum gb104 strain and composition comprising same for prevention or treatment of cancer |
CA3213447A CA3213447A1 (en) | 2021-03-22 | 2022-03-21 | Lactobacillus plantarum gb104 strain and composition comprising same for prevention or treatment of cancer |
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WO2024167277A1 (ko) * | 2023-02-06 | 2024-08-15 | 주식회사 지아이바이옴 | 락토바실러스 플란타룸 균주 및 면역세포의 병용 요법을 이용한 암 예방 또는 치료용 조성물 |
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WO2024063546A1 (ko) * | 2022-09-20 | 2024-03-28 | 주식회사 지아이바이옴 | 락토바실러스 플란타룸 균주의 병용 요법 및 이를 이용한 암 치료 방법 |
WO2024063543A1 (ko) * | 2022-09-20 | 2024-03-28 | 주식회사 지아이바이옴 | 락토바실러스 플란타룸 균주 및 한약재를 포함하는 병용 요법을 이용한 암 예방 또는 치료용 조성물 |
WO2024177440A1 (ko) * | 2023-02-24 | 2024-08-29 | 주식회사 지아이바이옴 | 락토바실러스 플란타룸 균주를 포함하는 항암보조제 |
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CN116144530A (zh) * | 2022-11-17 | 2023-05-23 | 朗恒科技集团有限公司 | 一株植物乳杆菌ay01及其应用 |
WO2024167277A1 (ko) * | 2023-02-06 | 2024-08-15 | 주식회사 지아이바이옴 | 락토바실러스 플란타룸 균주 및 면역세포의 병용 요법을 이용한 암 예방 또는 치료용 조성물 |
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US20240293484A1 (en) | 2024-09-05 |
CA3213447A1 (en) | 2022-09-29 |
KR20240007701A (ko) | 2024-01-16 |
CN117042786A (zh) | 2023-11-10 |
EP4316499A1 (en) | 2024-02-07 |
JP2024511269A (ja) | 2024-03-13 |
AU2022243439A1 (en) | 2023-10-12 |
KR102623045B1 (ko) | 2024-01-10 |
EP4316499A4 (en) | 2024-08-21 |
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