WO2021085853A1 - Composition pour améliorer l'activité immunitaire et procédé associé - Google Patents

Composition pour améliorer l'activité immunitaire et procédé associé Download PDF

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WO2021085853A1
WO2021085853A1 PCT/KR2020/012530 KR2020012530W WO2021085853A1 WO 2021085853 A1 WO2021085853 A1 WO 2021085853A1 KR 2020012530 W KR2020012530 W KR 2020012530W WO 2021085853 A1 WO2021085853 A1 WO 2021085853A1
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cells
cancer
cell therapy
immune cells
immune
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Korean (ko)
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예상규
김병학
이해리
노금희
정애진
이송희
김슬기
권용진
서은비
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서울대학교산학협력단
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Priority to CN202080077663.7A priority Critical patent/CN114667152B/zh
Publication of WO2021085853A1 publication Critical patent/WO2021085853A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0646—Natural killers cells [NK], NKT cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/80—Neurotransmitters; Neurohormones
    • C12N2501/825—Serotonine (5-HT); Melatonine
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/999—Small molecules not provided for elsewhere

Definitions

  • the present invention relates to a substance for activating immune cells and a method for activating immune cells using the same. More specifically, it relates to a composition capable of enhancing the immune activity of the immune cells by culturing them together with the immune cells when culturing the immune cells.
  • Pancreatic cancer is one of the common primary cancers, and less than 5% of all patients are malignant tumors with an average survival rate of 5 years after diagnosis. Compared to other carcinomas, it is known to be the only carcinoma that has not improved its average survival rate over several decades.
  • a method known as an effective treatment for pancreatic cancer is surgical removal. Since the tumor mass of pancreatic cancer is mainly composed of fibrous tissue and only a part of cancer cells, it is difficult to evaluate the treatment response to cancer after chemotherapy, and pancreatic cancer is known as a cancer that does not work well with chemotherapy. Possible surgical resection is recommended rather than chemotherapy.
  • An anticancer drug used clinically is gemcitabine (Eli Lilly and Company), but there are ongoing questions about the effectiveness of the treatment. However, there are no alternative substances and treatment methods available. Therefore, there is a demand for the development of an anticancer drug that can effectively treat pancreatic cancer and has a low side effect on use, or an adjuvant that can enhance the effect of existing anticancer drugs.
  • Natural killer cells a cell commonly used as one of the active ingredients of cell therapy products, are activated by several cytokines to amplify and secrete cytolytic functions.
  • the activated natural killer cells are interferon- It secretes gamma, tumor-necrosis factor (TNF), and autologous granulocyte/macrophage colony-stimulation factor (GM-CSF) together with chemokine to induce an inflammatory response. . It also affects adaptive immunity by inducing the differentiation and growth of monocytes, dendritic cells, and granulocytes (Prospects for the use of NK cells in immunotherapy of human cancer, NATURE REVIEWS, 2007).
  • polysaccharides derived from plants in addition to proteins such as interferon gamma have various macrophage functions, i.e., cytotoxic activity against tumor cells and microorganisms, phagocytic activity alpha-zoyonecrosis factor, and specific cytokines such as interleukin. It activates the secretion of kine and promotes cell differentiation and proliferation.
  • IFN- ⁇ interferon gamma
  • An object of the present invention is to provide a method of manufacturing a cell therapy product capable of enhancing the immune activity of immune cells, which is an active ingredient of a cell therapy product.
  • Another object of the present invention is to provide a composition for enhancing the therapeutic effect of a cell therapy agent for treatment or prevention of cancer.
  • the compound represented by Formula 1 corresponds to 5-nitro-2-furaldehyde p-hydroxybenzoylhydrazone, and'nifuroxazide (for example, it may also be expressed as AMBATROLTM, ANTINALTM, BACIFURANETM, DIAFURYLTM)'.
  • the compound represented by Formula 2 is 3-(2,4-dichloro-phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole (3-(2,4-dichloro Corresponds to -phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole).
  • the culture medium may contain melatonin.
  • melatonin is known to affect the circadian rhythm of physiological functions such as sleep timing, blood pressure control, and seasonal reproduction, among substances found in mammals, plants, bacteria, fungi, etc. Is one.
  • Melatonin may be used as'melatonin alone or in combination with at least one selected from ginsenoside and ⁇ -glucan (hereinafter, MTAM1).
  • MTAM1 can be used to cultivate lymphocytes, increases the proliferation rate of natural killer cells in immune cells obtained after cultivation, and further enhances the killing ability of the natural killer cells to cancer cells, so that cancer can be more effectively prevented or treated. .
  • the lymphocytes When culturing lymphocytes in an environment in which MTAM1 is present, the lymphocytes may be first cultured with CD3.
  • the MTAM1 may further include CD56, IL-18, or a combination thereof.
  • the cultivation of MTAM1 with an additional immune activating factor, CD3, CD56, IL-18, or a combination thereof, can be performed as needed, simultaneously, sequentially or crossover.
  • the "cellular therapeutic agent” refers to a drug (US FDA regulation) used for treatment, diagnosis, and prevention of cells and tissues manufactured through separation, cultivation and special manipulation from an individual. Or drugs used for treatment, diagnosis, and prevention through a series of actions such as proliferating and selecting live autologous, allogeneic, or xenogeneic cells in vitro to restore the function of tissues, or by changing the biological characteristics of cells in other ways. Means.
  • the cell therapy agent may contain immune cells as an active ingredient.
  • prevention refers to any action that inhibits or delays progression of cancer by administration of the composition of the present invention.
  • treatment and “improvement” mean all actions in which symptoms of cancer are improved or beneficially changed by administration of the composition of the present invention.
  • the "immune cells” may refer to all cells that are present in the body or have immune activity that can be separated from the body.
  • the immune cells may be, for example, natural killer cells, T cells, B cells, dendritic cells, macrophages, or a combination thereof.
  • the immune cells may be lymphocytes.
  • the immune cells may be natural killer cells (NK cells).
  • the compound of Formula 1 or 2 may contact isolated natural killer cells to enhance their immune activity.
  • the immune cells obtained from the human body are a mixture of various types of immune cells. Therefore, it is common to induce differentiation into specific immune cells during the culture process or to activate only their proliferation.
  • One embodiment of the present invention can successfully enhance its immune activity even when applied to isolated natural killer cells, as demonstrated in the following examples. This effect suggests that the expected immune activity can be obtained even in the final product of a cell therapy product containing pure natural killer cells as an active ingredient.
  • the “culture” refers to maintaining or preserving cells in a viable state, and may be meant to include exposing or contacting immune cells to a specific environment.
  • the compound represented by Formula 1 or 2, or a combination thereof may enhance the immune activity of immune cells by mixing and culturing them with immune cells.
  • the immune activity may mean, for example, cytotoxicity against cancer cells or infected cells. Ultimately, this can further enhance the cancer treatment or prevention effect of a cell therapy product containing immune cells as an active ingredient.
  • the cancer is, for example, pancreatic cancer, liver cancer, lung cancer, colon cancer, breast cancer, prostate cancer, ovarian cancer, colon cancer, cervical cancer, thyroid cancer, laryngeal cancer, leukemia, brain tumor, neuroblastoma, retinoblastoma, head and neck cancer, salivary gland cancer. , It may be selected from the group consisting of lymphoma, preferably pancreatic cancer.
  • Separating the immune cells from the culture may mean substantially removing components remaining in the culture medium and the culture medium in addition to the immune cells.
  • the separation method may use various methods such as membrane filtration, dialysis, precipitation method, cell adhesion and washing, etc., but is not limited thereto.
  • the step of isolating immune cells may be employed, but the compound represented by Formula 1 or 2, melatonin, or a combination thereof is only used for immune activity of immune cells. Since it is used in a small amount to enhance immunity, the effect on the individual may be very insignificant even if it remains with the immune cells.
  • the method of manufacturing the cell therapy agent may further include formulating the isolated immune cells as a cell therapy agent.
  • the formulation includes all actions of processing a cell therapy product into a form suitable for administration to an individual in need thereof, and may mean, for example, mixing the isolated immune cells with a pharmaceutically acceptable carrier.
  • Pharmaceutically acceptable carriers saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, liposomes, and one or more of these components may be mixed and used.
  • Other conventional additives such as an agent, a buffer solution, and a bacteriostatic agent, may be added.
  • diluents such as aqueous solutions, suspensions, emulsions, pills, capsules, granules, or tablets.
  • a target organ-specific antibody or other ligand may be used in combination with the carrier.
  • it can be preferably formulated according to each disease or component by an appropriate method in the art or by using a method disclosed in Remington's Pharmaceutical Science (latest edition), Mack Publishing Company, Easton PA. have.
  • the cell therapy agent may be a solution, a suspension, a dispersion, an emulsion, a gel, an injectable solution, a sustained-release preparation of the active compound, and the like, preferably an injection.
  • a buffer solution such as an acid aqueous solution or phosphate that can be used as an injection in order to ensure product stability according to the distribution of the injection formulation in the formulation step. It can be prepared as a very stable injection.
  • composition for enhancing the therapeutic effect of a cell therapy agent comprising the compound represented by Formula 1 or 2, melatonin, or a combination thereof.
  • composition for enhancing the therapeutic effect of the cell therapy agent may enhance the immune activity of immune cells, which is an active ingredient of the cell therapy agent, by contacting the cell therapy agent, and as a result, enhance the cancer treatment or prevention effect of the cell therapy agent.
  • composition for enhancing the therapeutic effect of the cell therapy agent may be used as an additive to a culture medium for culturing immune cells to contact immune cells.
  • the composition for enhancing the therapeutic effect of the cell therapy agent may be first mixed with the cell therapy agent before use in an individual in need of the cell therapy agent so that the cell therapy agent can exhibit rapid and efficient immune activity in an individual.
  • the compound represented by Formula 1 or 2 may be included in 1 ⁇ M to 100 ⁇ M, 1 ⁇ M to 80 ⁇ M, 1 ⁇ M to 60 ⁇ M, or 1 ⁇ M to 40 ⁇ M.
  • the composition for enhancing the therapeutic effect of the cell therapy agent may be removed from the mixture with the cell therapy agent before being administered to the subject to block unnecessary biological reactions in the subject.
  • the compound represented by Formula 1 or 2 is used in a small amount enough to enhance the immune activity of immune cells, even if administered as a mixture or remains, the effect on the individual is insignificant.
  • a first unit comprising a compound represented by Formula 1 or 2, melatonin, or a combination thereof; And it provides a kit comprising a second unit comprising a cell therapy product comprising immune cells as an active ingredient.
  • the "unit” is merely a means for distinguishing the composition of the kit, and may exist in the form of a solid, powder, solution, suspension, gel, etc., and may mean that it is included in an appropriate container that can be separated from each other .
  • the first unit and the second unit are separated in the kit and mixed with each other before use in an individual, thereby enhancing the immune activity of the immune cells of the second unit, thereby enhancing the therapeutic effect of the cell therapy product.
  • the kit may further include a component capable of separating immune cells from a mixture of the first unit and the second unit.
  • the configuration for separating the immune cells may be for substantially removing Formula 1 or 2, melatonin, or a mixture thereof from the mixture of the first unit and the second unit.
  • the components of the first unit are only small enough to enhance the immune activity of immune cells, even if administered as a mixture or remain, the effect on the individual is insignificant.
  • the description of the method of manufacturing the cell therapy agent may be interpreted in the same meaning as the description of the same configuration for the composition or kit for enhancing the therapeutic effect of the cell therapy agent.
  • the method for producing a cell therapy product using the compound represented by Formula 1 or 2, or a combination thereof provided in the present invention, and a composition therefor remarkably enhance the cell killing ability of immune cells against cancer cells or infected cells, thereby effectively enhancing immune cells. It is possible to remarkably improve the efficacy of cancer treatment or prevention of the cell therapy product included as an ingredient.
  • FIG. 3 to 6 are graphs showing cell surface antigens for each culture condition for test group 1, test group 2, and control group in Example 2, respectively, and FIG. 6 is a ratio of NK cells and NKT cells in cells harvested from each And the percentage of T cells.
  • Example 7 shows cell growth curves for test group 1, test group 2, and control group in Example 2.
  • Example 9 is a graph showing the results of a cell viability test for an immune cell activating substance according to the present invention in Example 2.
  • ROS reactive oxygen species
  • FIG. 12 is a graph showing the cell surface antigens of immune cells cultured and harvested after treatment with Test Group 1 on lymphocytes collected and isolated from blood in Example 2.
  • FIG. 12 is a graph showing the cell surface antigens of immune cells cultured and harvested after treatment with Test Group 1 on lymphocytes collected and isolated from blood in Example 2.
  • the present invention comprises the steps of culturing immune cells with a compound represented by Formula 1 or 2, melatonin, or a combination thereof; And it relates to a method for producing a cell therapy product comprising the immune cells as an active ingredient, comprising the step of isolating immune cells from the culture:
  • Example 1 Confirmation of the ability to enhance immune activity of immune cells of Formulas 1 and 2
  • Panc-1 a pancreatic cancer cell line
  • DMEM Dulbecco's modified Eagle's medium
  • NK-92 cells a natural killer cell line, were purchased from ATCC (Manassas, VA) and contain 20% FBS, 1% penicillin streptomycin, and 10 ng/ml recombinant human IL-2.
  • ATCC Manassas, VA
  • the NK-92 cells of Example 1-1 were each of Formulas 1 and 2 at a concentration of 1 ⁇ M, 5 ⁇ M, 10 ⁇ M, 20 ⁇ M, and 40 ⁇ M. Treated and incubated for 4 hours. Then, D-PlusTM cell viability assay kit (CCK-3000, Donginbiotech Co., Korea) was treated with 0.1X in a well-known manner, and absorbance at 450 nm was measured.
  • D-PlusTM cell viability assay kit (CCK-3000, Donginbiotech Co., Korea) was treated with 0.1X in a well-known manner, and absorbance at 450 nm was measured.
  • the survival rate was observed to be about 85% at all the tested concentrations, it was confirmed that there is no direct toxicity to NK-92 cells (Fig. 1).
  • LDH cytotoxicity detection kit Takara, Japan
  • NK-92 cells cultured with Formulas 1 and 2 had remarkably superior killing ability compared to the control group for Panc-1 cells (FIG. 2).
  • Example 2 Confirmation of the ability of melatonin to increase immune activity of immune cells
  • Lymphocytes were isolated from the patient's blood, suspended in a culture solution, and placed in a T-25 flask in which CD3 was solidified. Then, D56 5 ⁇ m and 10% of autologous plasma were added to the T-25 Flask and then cultured in a 37°C, 5% CO 2 incubator for 1-2 days. After being transferred to a T-75 Flask, it was incubated for 3-4 days in an incubator at 37°C and 5% CO 2.
  • test groups 1 and 2 were treated with 10 ⁇ l or 20 ⁇ l of MTAM1, respectively, in a T-175 flask, and 5% of autologous plasma was added. In addition, 5% of autologous plasma was added to the control group for comparison, and then incubated in a CO 2 incubator for 48 hours.
  • test groups 1 and 2 treatment with IL-18 and MTAM1 in the cell suspension cultivated in a T-175 flask, and after observing the activated state of the cells, the T-150 flask was incubated with a gas permeability of 1000 ml. After transferring to the culture medium containing the bag, it was cultured for 7 to 9 days to proliferate a large amount of cells.
  • the T-150 Flask was transferred to a culture medium containing a 1000 ml of gas-permeable culture bag, and then cultured for 7 to 9 days to proliferate a large amount of cells.
  • test groups 1 and 2 and the control group For each of the test groups 1 and 2 and the control group, cells containing a 1000 ml of CO 2 gas permeable culture bag and the culture solution were divided into 500 ml centrifuge tubes, and centrifuged for 17 minutes to harvest the cells. After the supernatant was carefully discarded so that the cells did not fall, the cells were washed with 250 ml of sterile physiological saline. The cells were harvested by rebalanced in the centrifuge, placed in a centrifuge tube, and centrifuged for 15 minutes. After carefully discarding the supernatant so that the cells do not fall off, 30 ml of a 100 ml sterile physiological saline bag for injection was collected using a syringe. The cells were suspended in 30 ml sterile physiological saline for injection. The suspended cells were poured into a cell strainer and filtered. The filtered cell suspension was placed in a sterile physiological saline bag for injection and suspended.
  • FIGS. 3 to 6 are graphs of cell surface antigen tests for each culture condition for test group 1, test group 2, and control group, respectively, and FIG. 6 shows the ratio of NK cells and NKT cells, and T cell ratios for each. .
  • Test group 1 Test group 2 Cell count Survival rate Cell count Survival rate Cell count Survival rate 2.26X10 9 83% 2.96X10 9 97% 3.86X10 9 95%
  • Test group 2 Sample name IMBIO_NK+T cell_01 IMBIO_NK+T cell_04 IMBIO_NK+T cell_04 Cytotoxic activity (%) 31 68 59
  • MTAM1 contains at least one of plant-derived melatonin, ginsenoside and ⁇ -glucan, preferably includes all of melatonin, ginsenoside and ⁇ -glucan.
  • NK cells are regulatory lymphocytes of the innate immune system that control different types of tumors by limiting growth and proliferation, exert direct cellular cytotoxicity without other stimuli, and produce IFN- ⁇ and hypoimmune-promoting cytokines. It can be secreted to control both local tumor growth and metastasis.
  • NK cells activated by IL-2 are similar to CTL, and after successively killing target cells by perforin and granzyme B, they survive. At this time, IL-2 Has the ability to accumulate granules and cytotoxicity of depleted NK cells.
  • NK cells have antibody dependent cellular cytotoxicity (ADCC).
  • ADCC antibody dependent cellular cytotoxicity
  • Fc ⁇ RIII CD16
  • Fc ⁇ RIII CD16
  • the activity of the Fc receptor induces the activity of NK cells to induce the secretion of cytolytic cytokines, and the ADCC action of these NK cells is a characteristic that only NK cells different from CTL have.
  • Melatonin has the effect of increasing the function of lymphocytes by increasing the production of glutathione by lymphocytes.
  • IFN- ⁇ and cytokines such as Interleukin-1, 2, 6, 12 (Interleukin-1, 2, 6, 12) through the melatonin receptor on the surface of monocytes, it induces the activity of NK cells.
  • MTAM1 according to the present invention increases the killing ability of NK cells against virus-infected cells and cancer cells, and increases cell viability by inhibiting free radicals in culture.
  • Ginsenoside activates C-SRC kinase and increases intracellular calcium ion concentration by 2 to 3 times.
  • the activation of the C-Src kinase-related pathway, which is an early stage of the intracellular signaling system, and the increase of intracellular calcium ions increase the expression of specific genes and promote cell proliferation.
  • ginsenoside-Rp1 induces the production of immune cytokines at a specific concentration in dendritic cells and increases the activity of NK cells at low concentrations.
  • beta-glucan increases the expression of TNF- ⁇ and IFN- ⁇ , and exhibits an anti-apoptosis effect in neutrophils.
  • Picarine a glucan isolated from Laminaria digitata, increases phagocytic activity, increases the production and secretion of IL-1, IL-6, and TNF- ⁇ , as well as picarine is complementary. Increases cancer cell death by NK cells through the third receptor (CR3).
  • FIG. 9 is a graph showing the results of a cell viability test for MTAM1, showing that MTAM1 according to the present invention has no intracellular toxicity, and further shows that it has an effect on proliferation.
  • FIGS. 10 and 11 are graphs showing the measurement results of Reactive Oxygen Species (ROS), and it was confirmed through FIG. 10 that ROS was artificially increased in NK cells to decrease ROS after MTAM1 treatment, and FIG. 11 As a result of measuring ROS after culturing NK cells in a medium containing MTAM1 for 14 days, it was confirmed that melatonin blocks free radicals.
  • ROS Reactive Oxygen Species
  • H 2 0 2 represents a stimulator that increases active oxygen
  • NAC represents a ROS scavenger.
  • the present invention relates to a substance for activating immune cells and a method for activating immune cells using the same. More specifically, it relates to a composition capable of enhancing the immune activity of the immune cells by culturing them together with the immune cells when culturing the immune cells.

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Abstract

La présente invention concerne une substance pour activer des cellules immunitaires lorsqu'elle est ajoutée à un milieu de culture pendant la culture des cellules immunitaires, et un procédé d'activation de cellules immunitaires l'utilisant, dans lequel la capacité de cellules immunitaires à tuer des cellules cancéreuses ou des cellules infectieuses est significativement améliorée, et ainsi, l'efficacité de traitement ou de prévention du cancer d'un agent thérapeutique cellulaire comprenant des cellules immunitaires en tant que principe actif peut être remarquablement améliorée.
PCT/KR2020/012530 2019-11-01 2020-09-17 Composition pour améliorer l'activité immunitaire et procédé associé WO2021085853A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010235611A (ja) * 2010-05-10 2010-10-21 Ortho Mcneil Pharmaceut Inc 腫瘍の治療のための細胞治療方法
US20170007698A1 (en) * 2014-02-05 2017-01-12 Cedars-Sinai Medical Center Methods and compositions for treating cancer and infectious diseases
KR20180136195A (ko) * 2017-06-14 2018-12-24 순천향대학교 산학협력단 줄기세포를 멜라토닌 처리 하여 증식 촉진 또는 생존율을 증가시키는 방법
WO2019006464A1 (fr) * 2017-06-30 2019-01-03 Memorial Sloan Kettering Cancer Center Compositions et méthodes de thérapies cellulaires adoptives contre le cancer

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101674463B1 (ko) * 2013-04-03 2016-11-10 서울대학교산학협력단 Ｓｔａｔ３ 저해활성을 갖는 화합물 및 이의 용도

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010235611A (ja) * 2010-05-10 2010-10-21 Ortho Mcneil Pharmaceut Inc 腫瘍の治療のための細胞治療方法
US20170007698A1 (en) * 2014-02-05 2017-01-12 Cedars-Sinai Medical Center Methods and compositions for treating cancer and infectious diseases
KR20180136195A (ko) * 2017-06-14 2018-12-24 순천향대학교 산학협력단 줄기세포를 멜라토닌 처리 하여 증식 촉진 또는 생존율을 증가시키는 방법
WO2019006464A1 (fr) * 2017-06-30 2019-01-03 Memorial Sloan Kettering Cancer Center Compositions et méthodes de thérapies cellulaires adoptives contre le cancer

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
LEE HAERI, JEONG AE JIN, YE SANG-KYU: "Highlighted STAT3 as a potential drug target for cancer therapy", BMB REPORTS, vol. 52, no. 7, 31 July 2019 (2019-07-31), pages 415 - 423, XP055807224, DOI: 10.5483/BMBRep.2019.52.7.152 *
NELSON ERIK A, WALKER SARAH R, KEPICH ALICIA, GASHIN LAURIE B, HIDESHIMA TERU, IKEDA HIROSHI, CHAUHAN DHARMINDER, ANDERSON KENNETH: "Nifuroxazide inhibits survival of multiple myeloma cells by directly inhibiting STAT3", BLOOD, vol. 112, no. 13, 15 December 2008 (2008-12-15), pages 5095 - 5102, XP055807219, DOI: 10.1182/blood *
ZHAO TIESUO, JIA HUIJIE, CHENG QIAN, XIAO YALI, LI MINMING, REN WENJING, LI CHEN, FENG YUCHEN, FENG ZHIWEI, WANG HUI, ZHENG JUNNIA: "Nifuroxazide prompts antitumor immune response of TCL-loaded DC in mice with orthotopically-implanted hepatocarcinoma", ONCOLOGY REPORTS, NATIONAL HELLENIC RESEARCH FOUNDATION, vol. 37, no. 6, 1 June 2017 (2017-06-01), pages 3405 - 3414, XP055807216, ISSN: 1021-335X, DOI: 10.3892/or.2017.5629 *

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