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Application of combined medication of bacteroides fragilis and PD-1 or PD-L1 antibody to treatment of genitourinary system cancer

A Bacteroides fragilis, PD-L1 technology, applied in the direction of antibody medical components, antibodies, applications, etc., can solve the problem of no PD-1/PD-L1 antibody microecological preparations, etc., to enhance the body's anti-tumor immune response, The effect of improving immune cell status

Active Publication Date: 2022-05-03
GUANGZHOU ZHIYI PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] Although there is a good interaction between gut flora and PD-1 / PD-L1 antibodies, there are no microecological agents specifically developed to enhance the efficacy of PD-1 / PD-L1 antibodies

Method used

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  • Application of combined medication of bacteroides fragilis and PD-1 or PD-L1 antibody to treatment of genitourinary system cancer
  • Application of combined medication of bacteroides fragilis and PD-1 or PD-L1 antibody to treatment of genitourinary system cancer
  • Application of combined medication of bacteroides fragilis and PD-1 or PD-L1 antibody to treatment of genitourinary system cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Embodiment 1 Bacteroides fragilis living bacteria liquid, the preparation of inactivated bacteria liquid

[0051] Streak inoculation of Bacteroides fragilis ZY-312 strain on blood plate, anaerobic culture for 48h. Observe the colony morphological characteristics, staining characteristics, size, club shape and distribution, etc.

[0052] Colony characteristics: After Bacteroides fragilis ZY-312 was cultured on a blood plate at 37°C for 48 hours, it was slightly convex, translucent, white, smooth, non-hemolytic, and the diameter of the colony was between 1mm and 3mm. See figure 1 .

[0053] Morphology under the microscope: Bacteroides fragilis ZY-312 was examined by Gram staining. It is a Gram-negative bacterium with a typical rod shape, blunt rounded ends and dense staining. The uncolored part in the middle of the bacteria is like a vacuole. figure 2 .

[0054] A single colony was selected and inoculated in a plant-derived peptone liquid medium for fermentation and c...

Embodiment 2

[0056] Example 2 Bacteroides fragilis combined with PD-1 antibody in the treatment of 4T1 breast cancer xenografts in mice

[0057] Experimental design: 70 BALB / c female mice were selected and randomly divided into 7 groups according to body weight range, namely blank group, model group, ZY-312 (10 10 CFU / piece), PD-1 antibody (PD-1ab) group (product number BE0146, purchased from BioXcell, the same 200 μg / piece), ZY-312 live bacteria combined with PD-1 antibody group, ZY-312 inactivated bacteria group (10 10 cell / rat), ZY-312 inactivated bacteria combined with PD-1 antibody group, 10 rats in each group. Except the blank group, animals in other groups were inoculated with 1×10 6 4T1 cells, the tumor volume reaches 100-150mm 3 Dosing in groups was started at D0: starting from D0, animals in the blank group and the model group were orally administered 300 μL of normal saline daily, and intraperitoneally injected with 200 μL of PBS twice a week; The administration volume of th...

Embodiment 3

[0096] Example 3 Bacteroides fragilis combined with PD-1 antibody in the treatment of mouse ID8 ovarian cancer ascites tumor

[0097] 1. Experimental design and process

[0098] 70 C57BL / 6 female mice aged 4-6 weeks were randomly divided into 7 groups according to the weight range, namely blank group, model group, ZY-312 (10 10 CFU / body), PD-1 antibody (PD-1ab) group (BE0273, BioXcell 200μg / piece), ZY-312 live bacteria combined with PD-1 antibody group, ZY-312 inactivated bacteria group (10 10 CFU / only), ZY-312 inactivated bacteria combined with PD-1 antibody group (10 10 CFU / only), 10 in each group.

[0099] Using DMEM culture solution containing 10% calf serum, penicillin (100U / mL) and streptomycin (100U / mL) under normal conditions (37°C, saturated humidity, 5% CO 2 ) to culture ID8 ovarian cancer cells to the logarithmic growth phase, adjust the cell concentration to 2×10 7 cells / mL, except for the blank group, each mouse in each group was intraperitoneally injected wit...

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Abstract

The invention discloses application of drug combination of bacteroides fragilis and a PD-1 antibody and / or a PD-L1 antibody in prevention and treatment of tumors of a genitourinary system. A large number of experiments prove that the bacteroides fragilis, especially the bacteroides fragilis ZY-312 with the preservation number of CGMCC No.10685, can be used for effectively preventing and treating the tumors of the genitourinary system by regulating immune factors, improving the state of immune cells and enhancing the anti-tumor immune response of a body.

Description

[0001] The microbial strains used in the implementation of the present invention have been preserved on April 2, 2015 at the General Microbiology Center (CGMCC) of the China Microbiological Culture Collection Management Committee (No. 3, No. 1, Beichen West Road, Chaoyang District, Beijing). Taxonomic designation: Bacteroides fragilis ZY-312 (Bacteroides fragilis ZY-312), deposit number CGMCC No.10685. Bacteroides fragilis ZY-312 was isolated and obtained by the applicant unit of the present invention, and has been authorized for patent protection (patent number 201510459408.X). According to the provisions of the patent examination guidelines, the public can buy it from commercial channels or has authorized it without preservation, that is, No deposit certificate is required. technical field [0002] The invention relates to an application technology of Bacteroides fragilis, in particular to the application of co-administration of Bacteroides fragilis and PD-1 antibody or PD-L...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K35/741A61P35/00A23C9/152A23C9/16A23C19/09A23G9/36A23L7/104A23L33/10A23L33/135
CPCA61K39/3955A61K35/741A61P35/00A23C9/16A23C9/152A23C19/09A23G9/36A23G9/363A23L7/104A23L33/10A23L33/135A23V2002/00A61K2300/00A23V2200/308A23V2200/324Y02A50/30
Inventor 吴嘉棋王从峰倪赛陈佳
Owner GUANGZHOU ZHIYI PHARMA INC
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