WO2021049587A1 - 抗体医薬の効果増強用組成物 - Google Patents

抗体医薬の効果増強用組成物 Download PDF

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WO2021049587A1
WO2021049587A1 PCT/JP2020/034361 JP2020034361W WO2021049587A1 WO 2021049587 A1 WO2021049587 A1 WO 2021049587A1 JP 2020034361 W JP2020034361 W JP 2020034361W WO 2021049587 A1 WO2021049587 A1 WO 2021049587A1
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antibody
glucan
group
antibody drug
composition
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English (en)
French (fr)
Japanese (ja)
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康 梨井
真之 藤野
▲祐▼生子 守屋
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National Center for Child Health and Development
Aureo Co Ltd
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National Center for Child Health and Development
Aureo Co Ltd
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Priority to CN202510792626.9A priority Critical patent/CN120678911A/zh
Priority to CN202080061449.2A priority patent/CN114340669A/zh
Priority to US17/631,704 priority patent/US12377116B2/en
Priority to EP20862447.8A priority patent/EP4029509A4/en
Priority to JP2021545597A priority patent/JP7088502B2/ja
Publication of WO2021049587A1 publication Critical patent/WO2021049587A1/ja
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2827—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant

Definitions

  • the present invention relates to a composition for enhancing the effect of an antibody drug.
  • Immune checkpoints are a braking mechanism to prevent such runaway so that activated immune cells do not attack even normal tissues and cells, and cancer cells are the opposite. This mechanism is used to avoid the attack of immune cells. This is one of the functions of cancer cells to survive themselves, and it is also a part that has not been clarified so far. With the progress of this research, in recent years, it has been clarified that clinically effective anti-cancer effects can be obtained with antibody drugs that inhibit the functions of immune checkpoint molecules PD-1 and CTLA4, and immune checks Research and development of point inhibitors are being carried out even more actively (see Non-Patent Documents 1 to 3).
  • Patent Document 1 a culture of Aureobasidium pullulans, which is also known as black yeast, which produces abundant ⁇ -glucan, as a moisturizer for skin (Patent Document 1) and an agent for improving constipation.
  • Patent Document 2 a culture of Aureobasidium pullulans, which is also known as black yeast, which produces abundant ⁇ -glucan, as a moisturizer for skin (Patent Document 1) and an agent for improving constipation.
  • Patent Document 2 immunostimulator
  • Patent Document 4 immunoadjuvant
  • Patent Document 5 biological healing promoter used to reduce side effects of anticancer agents
  • Biohealing promoter used for promotion (Patent Document 6), composition for preventing / treating bovine mammitis (Patent Document 7), composition for promoting cytokine production in macrophages (Patent Document 8), influenza virus infection (Patent Document 9), a TRAIL expression enhancer (Patent Document 10), an anemia prevention / amelioration composition (Patent Document 11), a fat accumulation inhibitor (Patent Document 12), and the like are disclosed.
  • An object of the present invention is to provide a composition capable of enhancing the effect of an antibody drug such as an immune checkpoint inhibitor by utilizing Aureobasidium pullulans.
  • ⁇ -glucan contained in the culture of Aureobasidium pullulans can be used in combination with an antibody drug such as an immune checkpoint inhibitor.
  • an antibody drug such as an immune checkpoint inhibitor.
  • a composition for enhancing the effect of an antibody drug which contains ⁇ -glucan as an active ingredient and is administered together with the antibody drug.
  • ⁇ -glucan is used as an active ingredient, the effect of the antibody drug can be enhanced by administering it together with the antibody drug. Therefore, it is suitably used as a strengthening agent such as an immune checkpoint inhibitor.
  • Test Example 2 It is a chart which shows the outline of the administration schedule of each test substance in Test Example 1. It is a chart which shows the result of having examined the tumor volume after the lapse of a predetermined number of days from the tumor cell transplantation in Test Example 1.
  • Test Example 2 the spleen lymphocytes were subjected to multiple staining with an anti-mouse CD4 antibody or an anti-mouse CD8 antibody, and an anti-mouse Ki-67 (lymphocyte activation marker) antibody, and FACS analysis was performed. is there.
  • TIL tumor-infiltrating lymphocytes
  • anti-mouse CD4 antibody or anti-mouse CD8 antibody and anti-mouse Ki-67 (lymphocyte activation marker) antibody
  • FACS analysis was performed. It is a chart which shows.
  • FIG. 5 is a chart showing the results of FACS analysis by multiple staining of spleen lymphocytes with anti-mouse CD4 antibody or anti-mouse CD8 antibody and anti-mouse INF- ⁇ antibody in Test Example 2.
  • TIL tumor infiltrating lymphocyte
  • an anti-mouse CD4 antibody an anti-mouse CD8 antibody
  • an anti-mouse INF- ⁇ antibody an anti-mouse INF- ⁇ antibody
  • FACS analysis was performed. It is a chart which shows the outline of the administration schedule of each test substance in Test Example 3. It is a chart which shows the result of having examined the tumor volume after the lapse of a predetermined number of days from the tumor cell transplantation in Test Example 3.
  • ⁇ -glucan is used as an active ingredient of a composition for enhancing the effect of an antibody drug.
  • ⁇ -glucan is a polysaccharide in which ⁇ -glucose is polymerized by glycosidic bond.
  • grains such as barley and oats, yeasts such as beer yeast and baker's yeast, incomplete fungi such as black yeast, basidiomycetes such as Shiitake, Maitake, Kawaratake, Suehirotake, Sparassis crispa, and Mannentake, and seaweeds such as kelp and wakame. Since it is contained in fungi and the like, it can be obtained by extracting from those natural products using an appropriate solvent or the like. As the extraction method, the conventional method may be followed, and there is no particular limitation.
  • an extraction solvent such as water or hydroalcohol
  • the heating conditions are typically 105 to 135 ° C.
  • the pressurization conditions are typically 1.8 to 2.1 atm.
  • extraction may be performed while performing acid treatment, alkali treatment, or enzyme treatment with an enzyme that lowers the molecular weight of the polysaccharide.
  • the solvent may be distilled off and concentrated, or the powder may be dried and powdered by a drying means such as spray drying.
  • various ⁇ -glucan materials have been distributed, and such commercially available products may be used.
  • the ⁇ -glucan used in the present invention is preferably polymerized by a ⁇ -1,3 glycosidic bond, a ⁇ -1,4 glycosidic bond, a ⁇ -1,6 glycosidic bond, or the like, and has a ⁇ -1,3 glycosidic bond. It is more preferable that the homopolymerization is contained as the main chain, or that the heteropolymerization of the ⁇ -1,3 glycosidic bond and the ⁇ -1,6 glycosidic bond is contained as the main chain, and the homopolymerization of the ⁇ -1,3 glycosidic bond is carried out. It is even more preferable that it is contained as a main chain and contains a ⁇ -1,6 glycosidic bond as a side chain.
  • the ⁇ -glucan may have a functional group such as a sulfate group or a phosphoric acid group.
  • the molecular weight is preferably in the range of an average molecular weight of 50 to 1,000,000, and more preferably in the range of an average molecular weight of 200,000 to 500,000.
  • the molecular weight of ⁇ -glucan can be measured by a gel filtration method or the like.
  • the ⁇ -glucan used in the present invention is a ⁇ -glucan-containing culture composition derived from a culture of Aureobasidium pullulans or a ⁇ -glucan-containing culture composition derived from shiitake mushrooms, as shown in Examples described later. And so on.
  • the ⁇ -glucan-containing culture composition includes a culture itself obtained by culturing a microorganism belonging to Aureobasidium pullulans (hereinafter, may be referred to as “Aureobasidium pullulans”), or bacterial cells by centrifugation or the like. Not only the culture in which water was separated and removed, the concentrate of the culture, the diluted solution of the culture, or the solid matter from which water was removed from the culture, but also these were desalted to identify ⁇ -glucan and the like. It also includes those with an increased content of the components of.
  • the aureobasidium pullulans used in the present invention may be any microorganism that belongs to Aureobasidium pullulans and has a ⁇ -glucan-producing ability.
  • Aureobasidium pullulans M-1 Aureobasidium pullulans. M-1, Trust number: FERM BP-08615, Trust date: Transferred from FERM P-19213 deposited on February 10, 2004 and February 14, 2003) (Patent of Independent Administrative Institution Product Evaluation Technology Infrastructure Organization) Biological Deposit Center Postal Code 292-0818, 2-5-8 Kazusa Kamashita, Kisarazu City, Chiba Prefecture, Japan Room 120), Aureobasidium pullulans M-2, Deposit No.
  • FERM BP-10014 Deposit Date : April 22, 2004
  • Patent Organism Depositary Center Postal Code 292-0818, 2-5-8 Kazusa Kamashita, Kisarazu City, Chiba Prefecture, Japan, Room 120 is preferably used.
  • the ⁇ -glucan produced by these strains was analyzed by NMR measurement (13CNMR: Varian UNITY INOVA500 type, 1HNMR: Varian UNITY INOVA600 type), and ⁇ -glucan was ⁇ -from the main chain to which glucose was ⁇ -1,3 bound. It has been clarified that it is ⁇ -1,3-1,6-glucan having a structure in which glucose is branched by -1,6 bond.
  • the above-mentioned aureobasidium microorganism can be cultured according to a known method (see JP-A-57-149301, etc.). That is, a medium containing 0.5 to 5.0% by mass of a carbon source (sucrose), 0.1 to 5.0% by mass of a nitrogen source (for example, rice bran), and other trace substances (for example, vitamins and inorganic substances).
  • the bacteria may be inoculated at pH 5.2 to 6.0) and aerated culture at a temperature of 20 to 30 ° C. for 2 to 14 days, preferably aeration stirring culture.
  • ⁇ -glucan is produced, the viscosity of the culture increases, resulting in a highly viscous gel.
  • the culture thus obtained usually contains 0.6 to 10% by mass of solid content, and the solid content contains 5 to 80% by mass of ⁇ -glucan.
  • the culture containing ⁇ -glucan obtained by the above culture is preferably used after being sterilized by heating or pressurizing. Further, the cells may be separated and removed by centrifugation or the like and then sterilized before use. Further, if necessary, a concentrated one or a dried one can be used. Further, an extracted component rich in ⁇ -glucan, or a desalted and purified product thereof can also be used.
  • the culture of microorganisms belonging to Aureobasidium pullulans is highly safe because it is used as a food additive such as a thickening stabilizer.
  • composition according to the present invention is used to be administered together with the antibody drug in order to enhance the effect of the antibody drug. That is, when the effect of an antibody drug is expressed for the purpose of anticancer effect or the like, it can be used to enhance the effect.
  • administered with an antibody drug is a range in which both the ⁇ -glucan or ⁇ -glucan-containing culture composition and the antibody drug component show their effectiveness in the biological composition of the tissue or cell to be applied. It suffices if they can be contacted in a timely manner, and it is not always necessary to administer both components in a single preparation. That is, the effects of the present invention can be enjoyed even if both components are continuously administered as separate preparations or administered at intervals of a predetermined time within the range showing the effectiveness.
  • the antibody drug to which the composition according to the present invention is applied is not particularly limited.
  • it may contain an antibody having an effect of suppressing the growth of cancer through immune checkpoint inhibition.
  • the types of diseases and cancers to which the antibody drug can be applied are not particularly limited, and if it is a cancer, for example, lung cancer, lymphoma, melanoma, leukemia, renal cell cancer, renal pelvis / urinary tract cancer, etc.
  • the antibody examples include, but are not limited to, anti-PD-L1 antibody, anti-PD-1 antibody, anti-LAG3 antibody, anti-CTLA4 antibody, anti-TIM3 antibody, anti-TIGIT antibody, anti-VISTA antibody and the like.
  • the antibody may be a polyclonal antibody, a monoclonal antibody, or an antiserum form containing the antibody. Further, it may be an antibody against a human protein, or may be an antibody against an animal protein such as a mouse, a rat, a rabbit, a goat, a cow, or a monkey. Further, it may be a human type antibody or an animal type antibody such as a mouse. Alternatively, it may be prepared by causing an animal such as a mouse, a rat, a rabbit, a goat, a cow, or a monkey to produce antiserum.
  • the administration route of the composition according to the present invention is not particularly limited, and a known formulation form is appropriately selected, and oral administration, intraperitoneal administration, intramuscular administration, nasal administration, pulmonary administration, vaginal administration, and intravenous administration. , It is possible to adapt to transrectal administration.
  • the dose of the composition according to the present invention can be appropriately determined depending on the type of antibody drug, the health condition, symptoms, age of the recipient or the recipient animal, the administration method, the number of administrations, the administration time, and the like.
  • the solid content of the ⁇ -glucan or ⁇ -glucan-containing culture composition is 0.025 to 4000 mg / kg (body weight).
  • Administer in volume in the case of intraperitoneal administration, the ⁇ -glucan or ⁇ -glucan-containing culture composition is administered in an amount of 0.05 to 5 mg / kg (body weight) in terms of solid content.
  • compositions according to the invention typically include, for example, pharmaceuticals, non-pharmaceutical products, functional foods, dietary supplements, supplements, health foods, veterinary medicines, veterinary pharmaceutical products, veterinary functional foods, animals. It can be used in various product forms such as dietary supplements for animals, supplements for animals, and health foods for animals. Alternatively, it can be used in combination with those products. It may also be used in combination with various foods and drinks.
  • Aureobasidium pullulans M-2 (Aureobasidium pullulans M-2, Incorporated Administrative Agency Product Evaluation Technology Infrastructure Organization Patent Biological Deposit Center Accession No .: FERM BP-10014) was inoculated into a liquid medium and shaken at 24.5 ° C for 4 days. By finally culturing, ⁇ -glucan was produced in the culture medium. The ⁇ -glucan concentration was estimated to be approximately 6 mg / mL by the phenol sulphate method and the enzymatic method.
  • mice C57BL / 6 mice (Nippon SLC Co., Ltd.) were inoculated with 3 ⁇ 10 5 mouse melanoma cell lines B16F10 (RIKEN Biobank) into the flanks of the mice. , By growing the tumor for 16 days.
  • test animals were divided into four groups: an untreated group, an anti-PD-L1 antibody alone administration group, a ⁇ -glucan single administration group, and an anti-PD-L1 antibody and ⁇ -glucan combination administration group, and the N number was 26 animals in the untreated group, 18 animals in the PD-L1 antibody alone administration group, 6 animals in the ⁇ -glucan single administration group, and 9 animals in the anti-PD-L1 antibody and ⁇ -glucan combination group.
  • the untreated group will be referred to as the "control group”
  • the anti-PD-L1 antibody single administration group will be referred to as "test group 1”
  • test group 2 The combined administration group of anti-PD-L1 antibody and ⁇ -glucan may be referred to as "test group 3".
  • test group 1 the anti-mouse PD-L1 antibody (Clone:) was administered at the 8th and 12th days after the tumor cell transplantation. MIH5) was intraperitoneally administered at a dose of 200 ⁇ g / animal.
  • test group 2 the ⁇ -glucan-containing culture composition prepared in Production Example 1 was used at the 8th, 11th, and 14th days after the tumor cell transplantation. It was intraperitoneally administered at a dose of 30 mg / kg in terms of the amount of ⁇ -glucan.
  • test group 3 For the combined administration group of the anti-PD-L1 antibody and ⁇ -glucan (“test group 3”), the anti-mouse PD-L1 antibody and the ⁇ -glucan-containing culture composition prepared in Production Example 1 above were individually administered. At the same time point as the group, the mice were intraperitoneally administered at the same dose as each single administration group.
  • FIG. 1 shows an outline of the administration schedule of each test substance.
  • the major axis and the minor axis of the tumor were measured, and the tumor volume (mm 3 ) was recorded by the following formula. ..
  • Table 1 and FIG. 2 show the results of the tumor volume after a predetermined number of days have passed since the tumor cell transplantation.
  • Table 2 shows the results of statistical analysis of the Brown-Forsythe Test to determine the significance between the groups when the tumor volumes were compared on the 16th day after tumor cell transplantation.
  • test group 3 the tumor volume was significantly reduced in the combined administration group of the anti-PD-L1 antibody and ⁇ -glucan as compared with the untreated group (“control group”).
  • the reducing effect was statistically significantly observed as compared with the anti-PD-L1 antibody alone administration group (“test group 1”) and the ⁇ -glucan alone administration group (“test group 2”) (16). See day comparison).
  • anti-mouse CD4 antibody BioLegend Japan Co., Ltd.
  • anti-mouse CD8 antibody BioLegend Japan Co., Ltd.
  • anti-mouse Ki-67 lymphocyte activation marker
  • anti-mouse INF- ⁇ antibody Naippon Becton Dickinson Co., Ltd.
  • FACS analysis After staining the cell surface antigen, the intracellular antigen was stained. Fixation Buffer and Permeabilization Wash Buffer (BioLegend Japan Co., Ltd.) were used for staining the intracellular antigen.
  • FIG. 3 shows the results of FACS analysis by multiple staining of spleen lymphocytes with an anti-mouse CD4 antibody, an anti-mouse CD8 antibody, and an anti-mouse Ki-67 (lymphocyte activation marker) antibody.
  • FIG. 4 shows the results of FACS analysis of tumor-infiltrating lymphocytes (TIL) by multiple staining with anti-mouse CD4 antibody or anti-mouse CD8 antibody and anti-mouse Ki-67 (lymphocyte activation marker) antibody. Is shown.
  • FIG. 5 shows the results of FACS analysis by multiple staining of spleen lymphocytes with anti-mouse CD4 antibody or anti-mouse CD8 antibody and anti-mouse INF- ⁇ antibody.
  • FIG. 6 shows the results of FACS analysis by multiple staining of tumor-infiltrating lymphocytes (TIL) with anti-mouse CD4 antibody, anti-mouse CD8 antibody, and anti-mouse INF- ⁇ antibody.
  • TIL tumor-infiltrating lymphocytes
  • ⁇ Test Example 3> In the same manner as in Test Example 1, a cancer-bearing mouse was prepared by transplanting a tumor cell line, and it was investigated whether the administration of the test substance had an effect on the growth of the tumor. At that time, as a test substance, ⁇ -glucan derived from shiitake mushroom (“Micelle glucan”, manufactured by RL-JP Co., Ltd.) (hereinafter referred to as “Micelle ⁇ -glucan”) is used instead of ⁇ -glucan derived from aureobasidium pullulans. ) was used.
  • mice C57BL / 6 mice (Nippon SLC Co., Ltd.) were inoculated with 3 ⁇ 10 5 mouse melanoma cell lines B16F10 (RIKEN Biobank) into the flanks of the mice. , By growing the tumor for 13 days.
  • test animals were divided into four groups: an untreated group, a micelle ⁇ -glucan alone administration group, an anti-PD-L1 antibody alone administration group, and an anti-PD-L1 antibody and micelle ⁇ -glucan combination administration group.
  • There were 4 animals in the untreated group 2 animals in the micelle ⁇ -glucan alone administration group, 3 animals in the PD-L1 antibody alone administration group, and 3 animals in the anti-PD-L1 antibody and micelle ⁇ -glucan combination group.
  • the untreated group is referred to as "control group A”
  • the micelle ⁇ -glucan single administration group is referred to as "test group 1A”
  • test group 2A the anti-PD-L1 antibody single administration group
  • the combined administration group of anti-PD-L1 antibody and micelle ⁇ -glucan may be referred to as “test group 3A”.
  • test group A physiological saline was intraperitoneally administered at the 8th, 12th, and 14th days after the tumor cell transplantation.
  • test group 1A 100 mg / kg of micelle ⁇ -glucan was administered in terms of the amount of ⁇ -glucan at the 8th and 11th days after tumor cell transplantation. The dose was intraperitoneally administered.
  • test group 2A 200 ⁇ g / animal of anti-mouse PD-L1 antibody (Clone: MIH5) was administered at the 8th and 12th days after tumor cell transplantation. The dose was intraperitoneally administered.
  • test group 3A the anti-mouse PD-L1 antibody was applied to the tumor cells on the 8th and 12th days after the tumor cell transplantation in the same manner as described above. It was administered in the form of administration, and micelle ⁇ -glucan was intraperitoneally administered at a dose of 100 mg / kg in terms of the amount of ⁇ -glucan at the 8th and 11th days after tumor cell transplantation.
  • FIG. 7 shows an outline of the administration schedule of each test substance.
  • Table 3 and FIG. 8 show the results of the tumor volume after a predetermined number of days have passed since the tumor cell transplantation.
  • Table 4 shows the results of statistical analysis of the Brown-Forsythe Test to determine the significance between the groups when the tumor volumes were compared on the 12th day after the tumor cell transplantation.
  • test group 3A the tumor volume was significantly reduced as compared with the untreated group (“control group A”).
  • control group A the untreated group
  • test group 2A the anti-PD-L1 antibody alone administration group

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PCT/JP2020/034361 2019-09-11 2020-09-10 抗体医薬の効果増強用組成物 Ceased WO2021049587A1 (ja)

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Application Number Priority Date Filing Date Title
CN202510792626.9A CN120678911A (zh) 2019-09-11 2020-09-10 用于增强抗体药物的效果的组合物
CN202080061449.2A CN114340669A (zh) 2019-09-11 2020-09-10 用于增强抗体药物的效果的组合物
US17/631,704 US12377116B2 (en) 2019-09-11 2020-09-10 Composition for enhancing effect of antibody drug
EP20862447.8A EP4029509A4 (en) 2019-09-11 2020-09-10 Composition for enhancing effect of antibody drug
JP2021545597A JP7088502B2 (ja) 2019-09-11 2020-09-10 抗体医薬の効果増強用組成物

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Publication number Priority date Publication date Assignee Title
WO2022270559A1 (en) * 2021-06-22 2022-12-29 Sophy Inc. Beta-glucan for preventing and/or treating fibrosis and related diseases

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