WO2023103441A1 - Composition antitumorale et son utilisation - Google Patents

Composition antitumorale et son utilisation Download PDF

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Publication number
WO2023103441A1
WO2023103441A1 PCT/CN2022/113005 CN2022113005W WO2023103441A1 WO 2023103441 A1 WO2023103441 A1 WO 2023103441A1 CN 2022113005 W CN2022113005 W CN 2022113005W WO 2023103441 A1 WO2023103441 A1 WO 2023103441A1
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tumor
children
donors
fecal bacteria
antagonist
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WO2023103441A8 (fr
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朱永亮
朱蒙蒙
穆晓静
刘丹
马梦楠
陆敏
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Suzhou Precision Biotech Co Ltd
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Suzhou Precision Biotech Co Ltd
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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
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention relates to the technical field of medicine, in particular to an antitumor composition and its application.
  • Fecal microbiota transplantation is also known as intestinal microbial transplantation and fecal therapy. Fecal microbiota transplantation is to transplant the fecal flora of healthy donors into the digestive tract of patients through various methods, aiming to rebuild the intestinal flora of patients and thus To achieve the purpose of treating diseases inside and outside the intestinal tract. FMT has been recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection (CDI), and is gradually being applied to the treatment of other intestinal and intestinal diseases. However, due to the complex establishment of FMT methodology, there is no unified standard at home and abroad, resulting in large heterogeneity in the efficacy of various studies, which greatly limits the clinical application of FMT.
  • CDI recurrent or refractory Clostridium difficile infection
  • the gut of children contains many of the same microbiota as adults, but there are taxonomic and functional differences in age-related microbiota. Compared with adults, the gut microbiota of prepubertal children is enriched in the genera Bifidobacterium, Faecalibacterium, and Lachnospiraceae, which are involved in vitamin synthesis, amino acid degradation, phosphorus oxide acidification and mucosal inflammation, and there were significant differences in the relative abundance of these flora. In addition, the structure of children's intestinal flora is affected by geography and diet culture.
  • fecal bacteria capsules are mainly used to treat gastrointestinal diseases, and there are no reports of using them in the treatment of tumors, let alone reports of children's fecal bacteria capsules combined with PD-1 antagonists for the treatment of tumors.
  • the present invention provides an antitumor composition and its application.
  • the PD-1 antagonist and the children's fecal bacteria capsule are used in combination for the treatment of liver cancer, and it is found that they have a synergistically enhanced inhibitory effect on the growth of liver cancer tumor volume.
  • the invention provides an anti-tumor composition, comprising a PD-1 antagonist and children's fecal bacteria capsules; the children's fecal bacteria capsules are prepared from feces of healthy children aged 7-16.
  • the PD-1 antagonist is calculated by mass mg
  • the children's fecal bacteria capsule is calculated by the number of colonies in CFU
  • the ratio of the quality of the PD-1 antagonist to the number of colonies of the children's fecal bacteria capsule is ( 0.09 ⁇ 0.1): (2 ⁇ 10 6 ⁇ 2 ⁇ 10 8 ).
  • the ratio of the mass of the PD-1 antagonist to the number of colonies in the children's fecal bacteria capsule is 0.1:2 ⁇ 10 8 .
  • the children's fecal bacteria capsules are made by the following method:
  • Step 1 Select healthy children aged 7-16, conduct a health questionnaire survey, and obtain qualified donors after preliminary screening;
  • Step 2 using high-throughput sequencing to screen the qualified donors
  • Step 3 Perform clinical physical examination on the donors screened in step 2 to obtain target donors;
  • Step 4 Soak the feces of the target donor selected in step 3 in sterile saline, filter, centrifuge, take the precipitate and mix it with sterile saline to obtain a fecal liquid;
  • Step 5 Mix the fecal bacteria liquid prepared in step 4 and the freeze-drying protective agent, then freeze and dry in a vacuum, and put the obtained fecal bacteria freeze-dried powder into a capsule shell to obtain children's fecal bacteria capsules.
  • the health questionnaire survey includes: no gastrointestinal discomfort in the past 2 weeks, no use of antibiotics, antacids, immunosuppressants, chemotherapy drugs, etc. in the past 3 months, and no chronic pain Symptoms, no history of digestive system surgery, no history of infectious diseases and contact history of infectious diseases, no history of allergic diseases, autoimmune diseases, metabolic diseases, cardiovascular and cerebrovascular diseases, nervous system or mental diseases, no history of malignant tumors, no medical treatment Intravenous injections of growth hormone, insulin, blood coagulation factors, etc.; regular work and rest, healthy diet, harmonious family, no smoking, drinking or drug addiction, no drug addiction, no vaccinations or drug trials in the past 6 months, no tattoos Or skin damage and no contact with epidemic areas and tropical areas; no family history of gastrointestinal lesions, no family history of malignant tumors, no family history of infectious diseases; interviews with psychologists or psychological counselors believe that the patient's current mental state is good; depression Self-rating scale (SDS), self-rating anxiety scale (SAS),
  • high-throughput sequencing is used to identify whether the donor contains pathogenic bacteria, to screen out the donors without pathogenic bacteria, and to exclude potential risky donors, which is conducive to quality monitoring.
  • the method of screening donors using high-throughput sequencing comprises the steps of:
  • the microbial database in step (2) includes any one or a combination of at least two of bacterial genomes, fungal genomes or viral genomes derived from public databases.
  • the pathogenic bacteria database in step (3) includes pathogenic bacteria genomes derived from public databases.
  • the present invention utilizes public databases such as NCBI and KEGG to construct a microbial database and a pathogenic bacteria database, and compares the sequencing data of fecal bacteria donors to the above-mentioned databases to realize microbial identification at the strain level and exclude fecal bacteria donors carrying pathogenic bacteria. body, reducing health risks.
  • step 2 high-throughput sequencing is used to screen the fecal bacteria donors according to the biomarkers expressed by the fecal bacteria donors and the diversity index of the biomarkers.
  • the biomarkers include Escherichia coli (Escherichia coli), Clostridium ramosum, Eubacterium cylindroides, Roseburia hominis, Faecalibacterium prausnitzii), Bacteroides fragilis or Bacteroides vulgatus or a combination of at least two.
  • the diversity index of the biomarkers comprises an alpha diversity index of the biomarkers.
  • the biomarkers Escherichia coli Escherichia coli
  • Clostridium ramosum Clostridium ramosum
  • Eubacterium cylindroides Eubacterium cylindroides
  • human Rose Berry Roseburia hominis
  • Faecalibacterium prausnitzii Bacteroides fragilis
  • Bacteroides vulgatus and the ⁇ -diversity index of biomarkers as indicators for screening fecal donors.
  • the clinical examination includes: both medical and surgical physical examinations are negative; body mass index (BMI) is 18.5-23.9kg/m2; blood routine, liver and kidney function, electrolytes and C-reactive protein are normal; Hepatitis E, HIV1 and HIV2 antibodies, HTLV1 and HTLV2 antibodies, Treponema pallidum antibodies (TPHA, VDRL), EBV IgM and IgG, cytomegalovirus IgM and IgG, strongyloides IgG, amoebic dysentery serology negative; stool Routine examination was normal; occult blood test was negative; Clostridium difficile, Campylobacter, Vibrio, Salmonella, Shigella, Shiga toxin-producing E.
  • BMI body mass index
  • coli, Yersinia, and Orthomonas were negative; eggs, vesicles , parasites, microsporidia, giardia and cryptosporidium stool antigens, cyclospora and heterosporidium acid-fast staining test negative; norovirus, rotavirus, adenovirus, enterovirus test negative; multi-resistant Drug bacteria: carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum ⁇ -lactamase-producing bacteria (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) test was negative; Helicobacter pylori stool antigen test was negative; serum monogenic genetic disease was negative; stool novel coronavirus (COVID-19) was negative.
  • CRE carbapenem-resistant Enterobacteriaceae
  • ESBL extended-spectrum ⁇ -lactamase-producing bacteria
  • MRSA methicillin-resistant Staphy
  • the feces of the target donor are soaked in sterile saline, filtered, centrifuged, and the precipitate is mixed with sterile saline to obtain a feces liquid.
  • the temperature of the sterile physiological saline is 3-5°C, specifically 3°C, 4°C or 5°C.
  • the filtering is performed using a filter screen.
  • the pore size of the filter screen is 0.25-2mm, specifically 0.25mm, 0.5mm, 1.0mm or 2.0mm.
  • the filtering includes sequentially using 2.0mm, 1.0mm, 0.5mm and 0.25mm filter screens to remove large particles, and then using 0.25mm filter screens to filter 2 to 3 times, and the obtained liquid phase is feces filtrate .
  • the feces filtrate is centrifuged, and the precipitate is mixed with sterile saline to obtain a fecal bacteria liquid.
  • the rotational speed of the centrifugal treatment is 1500-3000r/min, specifically 1500r/min, 1600r/min, 1700r/min, 1800r/min, 1900r/min, 2000r/min, 2100r/min, 2200r/min , 2300r/min, 2400r/min, 2500r/min, 2600r/min, 2700r/min, 2800r/min, 2900r/min or 3000r/min.
  • the centrifugation time is 10-20 min, specifically 10 min, 11 min, 12 min, 13 min, 14 min, 15 min, 16 min, 17 min, 18 min, 19 min or 20 min.
  • the lyoprotectant includes skim milk powder, trehalose, sucrose, vitamin C and sterile saline. In some specific embodiments, the lyoprotectant includes, by mass percentage: 10% to 20% of skim milk powder, 10% to 15% of trehalose, 1% to 10% of sucrose, 1% to 5% of vitamin C, and the balance for normal saline.
  • the lyoprotectant can effectively prolong the survival time of the flora and improve the colonization effect of the flora.
  • the volume ratio of the feces liquid to the lyoprotectant is (2-5):1, specifically 2:1, 3:1, 4:1 or 5:1, preferably 3:1 .
  • the cooling and freezing conditions are 10-20s from room temperature to 3-6°C, 1-2°C/min from 3-6°C to -30--50°C, 4-5°C/min from- 30 ⁇ -50°C to -75 ⁇ -80°C.
  • the cooling time is 12-24 hours, specifically 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours or 24 hours.
  • the vacuum degree of the vacuum drying is 5-15 Pa, such as 5 Pa, 6 Pa, 7 Pa, 8 Pa, 9 Pa, 10 Pa, 11 Pa, 12 Pa, 13 Pa, 14 Pa or 15 Pa.
  • the vacuum drying temperature is -50 to -60°C, specifically -50°C, -51°C, -52°C, -53°C, -54°C, -55°C, -56°C , -57°C, -58°C, -59°C or -60°C.
  • the vacuum drying time is 24-48 hours, specifically 24 hours, 30 hours, 36 hours, 42 hours or 48 hours.
  • the capsule shell includes an enteric-coated capsule shell.
  • the enteric-coated capsule shell can effectively resist the decomposition of gastric juice, and the effective flora in the capsule will be released only under the pH value of the intestinal tract, which can effectively protect the flora from reaching the intestinal tract, prevent premature release of the flora, and reduce the loss of the activity of the flora , prolong the release time of the flora, achieve a specific colonization effect, and facilitate the realization of oral administration.
  • the children's fecal fungus capsules are stored at a temperature of -75 to -80°C.
  • the invention also provides the application of the anti-tumor composition in the preparation of medicines for inhibiting the growth of tumor volume.
  • said inhibiting tumor volume growth includes inhibiting growth and/or proliferation of tumor cells.
  • the invention also provides the application of the anti-tumor composition in the preparation of anti-tumor drugs.
  • the anti-tumor includes inhibiting the growth of tumor volume and/or inhibiting the migration of tumor cells.
  • children's fecal bacteria capsules and PD-1 antagonists are used in combination for tumor treatment, wherein the children's feces bacteria capsules and PD-1 antagonists can be administered simultaneously or successively in any order.
  • the specific dosage can be determined according to the specific condition of the tumor patient combined with the clinical experience of the doctor.
  • the effective dose of the Capsules spp. is 2 ⁇ 10 6 to 2 ⁇ 10 8 CFU/mouse
  • the effective dose of the PD-1 antagonist is 0.09 to 0.1 mg/mouse.
  • the effective dose of the children's fecal bacteria capsule is 2 ⁇ 10 8 CFU/mouse
  • the effective dose of the PD-1 antagonist is 5 mg/kg mouse body weight, that is, 0.09-0.1 mg/mouse.
  • the dosage of 5 mg/kg mouse weight converted into each mouse is 0.09-0.1 mg/mouse.
  • the present invention also provides an antitumor drug, including the antitumor composition described in the present invention.
  • the PD-1 antagonist is a PD-1 monoclonal antibody or an antigen-binding fragment thereof.
  • the PD-1 monoclonal antibody or its antigen-binding fragment specifically binds to PD-1, and blocks the binding of PD-1 and PD-L1.
  • the PD-1 monoclonal antibody or antigen-binding fragment thereof specifically binds to human PD-1, and blocks the binding of human PD-1 and human PD-L1.
  • the present invention has no special limitation on the source of the PD-1 antagonist, which can be purchased from any manufacturer. There are no special restrictions on its dosage forms, including but not limited to tablets, capsules, pills, granules, decoctions, ointments, dews, oral liquids, injections, dripping pills or syrups, preferably injections, such as injection powder and Injection solution.
  • the tumor is a solid tumor, specifically, the tumor is a cancer expressing PD-L, including but not limited to liver cancer, colon cancer, lung cancer and melanoma tumor. In some specific embodiments, the tumor is liver cancer.
  • Figure 1 shows the difference in flora before and after oral administration of fecal bacteria capsules in patients with irritable bowel syndrome and the relationship with donors;
  • Figure 2 is the PCA diagram of the differences between children and adults in healthy groups
  • Fig. 3 is the random forest modeling model of children and adult samples
  • Fig. 4 is the mouse body weight change figure after treatment group and control group administration
  • Figure 5 shows the relative tumor inhibition rate of each treatment group.
  • the invention provides an antitumor composition and its application.
  • Those skilled in the art can refer to the content of this article to appropriately improve the process parameters to achieve.
  • all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention.
  • the method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously make changes or appropriate changes and combinations to the method and application herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention Invent technology.
  • test materials used in the present invention are all common commercially available products, which can be purchased in the market.
  • Step 1 Choose healthy children aged 7-16 who have a healthy lifestyle, and have not experienced gastrointestinal discomfort in the past 2 weeks, and have not used antibiotics, antacids, immunosuppressants, chemotherapy drugs, etc. in the past 3 months, and have no chronic disease.
  • Step 2 Based on the qualified donors initially screened in step 1, further screening based on high-throughput sequencing technology, the steps are as follows:
  • Extract DNA from the feces of fecal bacteria donors construct a library for next-generation sequencing, and obtain original sequencing data; after removing the host genes of the original sequencing data, compare them with NCBI microbial databases (bacterial genomes, fungal genomes, and viral genomes). Carry out bacterial species identification and abundance detection; compare with the KEGG pathogenic bacteria database to confirm that there are no pathogenic bacteria in the donor.
  • NCBI microbial databases bacterial genomes, fungal genomes, and viral genomes.
  • Step 3 Conduct clinical physical examination on the donors screened in step 2: both medical and surgical physical examinations are negative; body mass index (BMI) is 18.5-23.9kg/m2; blood routine, liver and kidney function, electrolytes and C-reactive protein are normal; A and B Hepatitis B, HIV1 and HIV2 antibodies, HTLV1 and HTLV2 antibodies, Treponema pallidum antibodies (TPHA, VDRL), EBV IgM and IgG, cytomegalovirus IgM and IgG, strongyloides IgG, and amoebic dysentery serological tests were negative; Stool routine examination was normal; occult blood test was negative; Clostridium difficile, Campylobacter, Vibrio, Salmonella, Shigella, Shiga toxin-producing E.
  • BMI body mass index
  • coli, Yersinia, and Orthomonas were negative; eggs, cysts Negative acid-fast stain for vesicles, parasites, microsporidia, giardia, and cryptosporidium stool antigens, cyclosporine, and heterosporidium; negative for norovirus, rotavirus, adenovirus, enterovirus; multiplex Drug-resistant bacteria: carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum ⁇ -lactamase-producing bacteria (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterobacteriaceae Negative coccus (VRE) test; negative Helicobacter pylori stool antigen test; negative serum monogenic genetic disease; negative stool novel coronavirus (COVID-19).
  • CRE carbapenem-resistant Enterobacteriaceae
  • ESBL extended-spectrum ⁇ -lactamase-producing bacteria
  • MRSA meth
  • the feces of the healthy children screened in Example 1 were collected on-site, sent to the laboratory for information registration, feces identification, weighing, evaluation and processing within 1 hour, and prepared fecal bacteria liquid in an anaerobic environment, the steps are as follows:
  • Step 1 Soak the collected feces in sterile physiological saline at 5°C, use 2.0mm, 1.0mm, 0.5mm and 0.25mm filters in turn to remove large particles, and then use 0.25mm filter for 3 times to obtain the The liquid phase is fecal filtrate.
  • Step 2 centrifuge the feces filtrate at 3000r/min for 10min, take the precipitate and mix it with sterile physiological saline to obtain the fecal bacteria liquid.
  • Step 3 Mix the fecal bacteria liquid and the freeze-drying protective agent (15% of skimmed milk powder, 15% of trehalose, 5% of sucrose, 5% of vitamin C, and the balance is physiological saline) according to 3:1 (v/v), Then drop from room temperature to 4°C within 10s, and further drop from 4°C to -40°C at a rate of 2°C/min, and from -40°C to -80°C at a rate of 5°C/min. Vacuum-dried for 48 hours at a vacuum degree of 10 Pa and -50°C, and the obtained fecal bacteria freeze-dried powder was packed into an enteric-coated capsule shell to obtain the fecal bacteria capsule, which was stored at -80°C.
  • the freeze-drying protective agent (15% of skimmed milk powder, 15% of trehalose, 5% of sucrose, 5% of vitamin C, and the balance is physiological saline
  • 16S rRNA detection was performed on the stool samples of patients. At the level of family classification, the abundance of Firmicutes was significantly increased (p ⁇ 0.01), which was consistent with that of healthy donors.
  • biomarkers were screened out, including Bifidobacterium breve, Clostridioides difficile, Bifidobacterium catenulatum, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium kashiwanohense, Paeniclostridium sordellii, Bacteroides ster coris, Terrisporobacter petrolarius, Blautia wexlerae, found by analysis Both are Actinobacteria (Actinobacteria) and Firmicutes (Fimicutes).
  • n number of animals; PD-1 is formulated as 0.5mg/ml PD-1 solution, the administration volume is 10ul/g, and the PD-1 administration volume for each mouse (calculated as 20g body weight) is 200ul, converted The dosage is 0.1 mg/mouse, that is, the dosage is 5 mg/kg; the dosage of GZ is 2 ⁇ 10 8 CFU/mouse.
  • TGI% (1-T/C) ⁇ 100%.
  • T/C% is the relative tumor proliferation rate, at a certain time point, the percentage value of the relative tumor volume or tumor weight in the treatment group and the control group.
  • T and C are the relative tumor volume (RTV) or tumor weight (TW) of the treatment group and the control group at a specific time point, respectively.
  • T/C% T TW /C TW ⁇ 100% (T TW : the average tumor weight at the end of the experiment in the treatment group; C TW : the average tumor weight at the end of the experiment in the control group).
  • mice were subcutaneously inoculated with H22 cells to establish a subcutaneous transplanted tumor model of colon cancer in mice.
  • the test was divided into test drug children's feces capsules (2 ⁇ 10 8 CFU) group, adult feces capsules (10 8 CFU) group, positive control anti-PD-1 (5mg/kg) group and vehicle control group, each group 8 Only, the test drug was administered orally, every day, for a total of 18 days, and the positive control drug was administered by intraperitoneal injection, three times a week, for a total of 8 times.
  • the average tumor volume of mice in the vehicle control group was 1148 mm 3 on the 17th day after administration.
  • the average tumor volume in the treatment group of the test drug Children's Fecal Capsules (2 ⁇ 10 8 CFU) was 1382 mm 3 , which was not statistically significantly different from that in the control group.
  • the positive control anti-PD-1 (5mg/kg) treatment group had an average tumor volume of 476mm 3 on the 17th day after administration, which was statistically significantly different from that of the control group (p ⁇ 0.001), and the relative tumor inhibition rate TGI (%) is 59%.
  • the relative tumor inhibition rate of the children's fecal bacteria capsules + anti-PD-1 combination group was 71.4%, which was significantly better than that of the children's fecal bacteria capsules alone and anti-PD-1 alone.
  • the above results show that the combination of PD-1 antagonists and children's feces capsules has a synergistic and enhanced effect of inhibiting tumor growth, and has a significant effect on liver cancer.

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Abstract

L'invention concerne une composition antitumorale et son utilisation, et un médicament antitumoral. La composition antitumorale comprend un antagoniste de PD -1 et un microbiote fécal d'enfant encapsulé. Les expériences montrent que la combinaison de l'antagoniste de PD-1 et du microbiote fécal d'enfant encapsulé, qui ont des mécanismes d'action et des voies d'action complètement différents, peut améliorer de manière synergique l'immunité de l'organisme et ont des effets curatifs importants sur les cancers (tels que le cancer du foie) exprimant le PD-1; leurs effets sont nettement meilleurs que lorsqu'ils sont utilisés séparément.
PCT/CN2022/113005 2021-12-07 2022-08-17 Composition antitumorale et son utilisation Ceased WO2023103441A1 (fr)

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