Application of combination of bacteroides fragilis and immune checkpoint inhibitor in treatment of digestive system tumors

A technology of Bacteroides fragilis and immune checkpoints, which is applied in the direction of antineoplastic drugs, medical preparations containing active ingredients, antibodies, etc., can solve the problem of no microecological preparations, etc., to improve comprehensive curative effect, prevent occurrence and development, improve Quality of Life Effects

Pending Publication Date: 2022-04-26
GUANGZHOU ZHIYI PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Despite the favorable interplay between gut microbiota and immune-suppressive points, no microbiota agents have been developed specifically to enhance immune checkpoint inhibitors

Method used

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  • Application of combination of bacteroides fragilis and immune checkpoint inhibitor in treatment of digestive system tumors
  • Application of combination of bacteroides fragilis and immune checkpoint inhibitor in treatment of digestive system tumors
  • Application of combination of bacteroides fragilis and immune checkpoint inhibitor in treatment of digestive system tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Embodiment 1 Bacteroides fragilis living bacteria liquid, the preparation of inactivated bacteria liquid

[0050] 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.

[0051] 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 .

[0052] 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 .

[0053] 1) Select a single colony and inoculate it in a plant-derived peptone liquid medium for fermentation and cu...

Embodiment 2

[0056] Example 2 Application of Bacteroides fragilis combined with PD-1 antibody in the treatment of liver cancer

[0057] 1. Experimental method

[0058] Modeling of liver cancer tumor formation: In this example, 110 5-week-old ICR pure-line male mice, weighing about 22 g, were selected. Mouse liver cancer cell H22 (purchased from ATCC) in the logarithmic growth phase was taken, and the number of cells was adjusted to 1×10 with PBS. 7 cell / mL, inoculate 0.2 mL of cell suspension under the armpit of the right forelimb of the mouse, and a small tumor mass grows at the inoculation site of the mouse, indicating that the model is successfully established.

[0059] Experimental grouping: the average tumor volume reached about 68mm 3 Start group dosing. Randomly divided into 11 groups, namely blank group, model group, PD-1 antibody group (CD-0146, BioXcell, 15mg / kg), ZY-312 live bacteria group (10 10 CFU / only), ZY-312 inactivated bacteria group (10 10 Cells / only), ZY-312 live b...

Embodiment 3

[0091] Example 3 Application of Bacteroides fragilis combined with PD-1 antibody in the treatment of esophageal cancer

[0092] 1. Experimental method

[0093] In this example, 7-week-old C57BL / 6 female mice were selected for verification, and an esophageal cancer model was established. Esophageal cancer modeling: 4-nitroquinoline-1-oxide (4-NQO) was dissolved in 1,2-propanediol to make a liquid with a concentration of 5g / L, and diluted to a solution with a concentration of 5mg / mL. C57BL / 6 female mice were allowed to drink sterilized water containing 100 μg / mL 4-NQO for 10 weeks, and then changed to normal water. The C57BL / 6 esophageal cancer model was successfully established. Tumor volume up to 100mm 3 time (D0), they were randomly divided into 11 groups. Namely blank group, model group, PD-1 antibody group (CD-0146, BioXcell, 15mg / kg), ZY-312 live bacteria group (10 10 CFU / only), ZY-312 inactivated bacteria group (10 10 Cells / only), ZY-312 live bacteria combined with ...

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Abstract

The invention discloses an application of a combination of bacteroides fragilis and an immune checkpoint inhibitor in treatment of digestive system tumors, and particularly relates to a combination of bacteroides fragilis ZY-312 with the preservation number of CGMCC No.10685, inactivated bacteria of the bacteroides fragilis ZY-312 and the immune checkpoint inhibitor including a PD-1 antibody or a PD-L1 antibody, and the bacteroides fragilis ZY-312, the inactivated bacteria of the bacteroides fragilis ZY-312 and the immune checkpoint inhibitor including the PD-1 antibody or the PD-L1 antibody can be combined in vivo by increasing the proportion of CD4 + T cells and CD8 + T cells. By down-regulating the level of cell factors IL-10 in tumors or up-regulating the level of INF-gamma, the growth of transplanted tumors in mice can be effectively inhibited. The traditional Chinese medicine composition can also be combined with treatment means such as operation, radiotherapy and chemotherapy, so that the comprehensive curative effect is remarkably improved, the harm of radiotherapy and chemotherapy to the body is relieved, occurrence, development, relapse and metastasis of tumors are effectively prevented, and the living quality of patients is improved.

Description

technical field [0001] The invention relates to an application technology of Bacteroides fragilis, in particular to an application of Bacteroides fragilis combined with an immunosuppressant in treating digestive system tumors. Background technique [0002] Malignant tumors of the digestive system have become a major global public health problem and a leading cause of death. In China, tumors of the digestive system are responsible for more than 50% of cancer-related deaths. Although the treatment methods for malignant tumors such as surgery, chemotherapy, and radiotherapy have been continuously developed, the diagnosis and prognosis of tumors are still not optimistic. For patients with no chance of radical surgery or metastatic tumors, comprehensive treatment mainly based on systemic drug therapy is currently adopted. Systemic drug therapy mainly includes the use of chemotherapy drugs, molecular targeted drugs and immunotherapy. Immunotherapy is currently the most popular ...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K35/741A61K39/395A61P35/00
CPCA61K45/06A61K35/741A61K39/3955A61P35/00A61K2300/00Y02A50/30
Inventor 智发朝刘洋洋李平王晔
Owner GUANGZHOU ZHIYI PHARMA INC
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