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Application of combined medication of bacteroides fragilis zwitterionic capsular polysaccharide and immune checkpoint inhibitor to treatment of genitourinary system tumors

A technology of Bacteroides fragilis and immune checkpoint, which is applied in the field of biomedicine to prevent and treat genitourinary system tumors and enhance the body's anti-tumor immune response

Pending Publication Date: 2022-05-13
GUANGZHOU ZHIYI PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0028] Currently, there is no documented use of zwitterionic capsular polysaccharides from Bacteroides fragilis in combination with immune checkpoint inhibitors for the treatment of urogenital tumors

Method used

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  • Application of combined medication of bacteroides fragilis zwitterionic capsular polysaccharide and immune checkpoint inhibitor to treatment of genitourinary system tumors
  • Application of combined medication of bacteroides fragilis zwitterionic capsular polysaccharide and immune checkpoint inhibitor to treatment of genitourinary system tumors
  • Application of combined medication of bacteroides fragilis zwitterionic capsular polysaccharide and immune checkpoint inhibitor to treatment of genitourinary system tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0093] Example 1 Preparation of Bacteroides fragilis capsular polysaccharide A

[0094] (1) Streak-inoculate Bacteroides fragilis ZY-312 strains on blood plates, culture anaerobically for 48 hours, select a single colony and inoculate it in plant-derived peptone liquid medium for fermentation and culture for 8 hours (at a temperature of 37°C), and the obtained bacteria The solution was centrifuged and precipitated at 3000r / min, centrifuged for 15min, the supernatant was removed, and the precipitate was collected to obtain the Bacteroides fragilis ZY-312 sludge.

[0095] (2) Take 50g of the bacteria slime prepared in step (1), add 300g of purified water to resuspend the bacteria, adjust the pH to 3.5 with 1mol / L hydrochloric acid solution, extract at 100°C for 1.5h, cool to room temperature, and centrifuge at 12000g for 10min at room temperature , take the supernatant to obtain the crude sugar solution;

[0096] (3) The crude sugar solution is concentrated by ultrafiltration t...

Embodiment 2

[0099] Example 2 Drug efficacy test of Bacteroides fragilis zwitterionic capsular polysaccharides and immune checkpoint inhibitors in synergistic treatment of Renca renal carcinoma xenografts in mice

[0100] 1. Experimental design and process

[0101] (1) Animal modeling

[0102] Take 100 Kunming mice, male, SPF grade, body weight (20±2) g, and 80 of them were subcutaneously inoculated with 250 μL of Renca cells (concentration of 1×10 7 The tumor growth of the mice was observed every day, and tumor nodules of about 5 mm were seen at the injection site after 7 days, which was considered as a successful establishment of the renal cancer tumor-bearing mouse model.

[0103] (2) Animal grouping and administration

[0104] 60 mice successfully modeled were taken and randomly divided into 6 groups, 10 in each group, model group, capsular polysaccharide A (PSA, 100 μg / mouse, prepared by Example 1, the same below), PD-1 antibody (PD-1ab, product number BE0146, purchased from BioXcell...

Embodiment 3

[0117] Example 3 Application of Bacteroides fragilis Zwitterionic Capsular Polysaccharide and Immune Checkpoint Inhibitors in Synergistic Treatment of Transplanted Tumors of Bladder Cancer (Urothelial Carcinoma) in Mice

[0118] 1. Experimental design and process

[0119] (1) Animal modeling

[0120] Take 100 male BALB / C-nude mice, among which 80 nude mice were subcutaneously disinfected on the back, and each was inoculated with 0.2ml T24 cell suspension (the cell concentration was 2×10 7 / mL). After transplantation, the nude mice were kept in the SPF environment, and tumor nodules appeared at the inoculation site, and the texture was hard and other indicators were identified as tumor formation.

[0121] (2) Animal grouping and administration

[0122] 60 nude mice successfully modeled were randomly divided into 6 groups, 10 in each group, model group, capsular polysaccharide A (PSA, 100 μg / mouse) group, PD-1 antibody group (PD-1ab, BE0146, BioXcell 200 μg / mouse) and low (...

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Abstract

The invention discloses application of combined medication of bacteroides fragilis zwitterionic capsular polysaccharide and an immune checkpoint inhibitor in prevention and treatment of tumors of a genitourinary system. A large number of experiments prove that when the capsular polysaccharide A of the bacteroides fragilis, especially the bacteroides fragilis ZY-312 with the preservation number of CGMCC No.10685, and an immune checkpoint inhibitor are combined for medication, the anti-tumor immune response of a body can be enhanced by regulating and controlling the levels of T cells and anti-tumor immune factors, and then the aim of preventing and treating the tumors of the genitourinary system is achieved.

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 the field of biomedicine, in particular to the application of a zwitterionic capsular polysaccharide of Bacteroides fragilis and immune checkpoint inhibit...

Claims

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Application Information

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IPC IPC(8): A61K31/715A61K45/06A61K39/395A23C9/152A23C9/156A23C9/16A23C19/09A23G9/34A23G9/36A23K10/18A23K20/163A23L7/104A23L33/125A23L33/135A61P35/00C08B37/00
CPCA61K31/715A61K45/06A61K39/39558A61P35/00C08B37/0003A23L33/135A23L33/125A23C9/16A23C9/156A23C9/152A23C19/09A23G9/363A23G9/34A23L7/104A23K10/18A23K20/163A23V2002/00A61K2300/00A23V2200/308A23V2200/314A23V2250/51Y02A50/30
Inventor 常秀娟郭真刘洋洋王晔
Owner GUANGZHOU ZHIYI PHARMA INC
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