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Application of doxycycline in preparing drug for inhibiting myeloid-derived suppressor cells

An inhibitory cell, doxycycline technology, used in antibacterial drugs, drug combinations, tetracycline active ingredients, etc.

Inactive Publication Date: 2019-04-23
TIANJIN INT JOINT ACADEMY OF BIOTECH & MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] So far, the application of doxycycline as an inhibitor of Myeloid-derived suppressor cells (MDSC) and prevention of cytokine storm induced by PD-1 therapy has not been reported

Method used

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  • Application of doxycycline in preparing drug for inhibiting myeloid-derived suppressor cells
  • Application of doxycycline in preparing drug for inhibiting myeloid-derived suppressor cells
  • Application of doxycycline in preparing drug for inhibiting myeloid-derived suppressor cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1 Doxycycline can reduce the content of MDSCs in tumor-bearing mice and improve the immunosuppressive microenvironment

[0035] 1. In vivo experiments to detect the inhibitory effect of doxycycline on B16-F10 subcutaneous xenograft tumor model and its effect on MDSC

[0036] 1.1 Establishment of subcutaneous xenograft model of B16-F10 melanoma

[0037] Will 4*10 5 B16-F10 cells were subcutaneously injected into the anterior axilla of C57BL / 6 mice to establish a subcutaneous xenograft model of B16-F10 melanoma. When the tumor reaches 100-200mm 3 , Divide the mice into four groups equally, 10 in each group.

[0038] 1.2 Administration

[0039] The control group was only given normal saline; the doxycycline group was orally injected with doxycycline at a dose of 50 mg / kg / day, and the PD-1 inhibitor group was intraperitoneally injected with PD-1 antibody (clone RMP1-14, Bio Xcell, 200μg / injection); Doxycycline and PD-1 combined group 50mg / kg / day oral injection ...

Embodiment 2

[0060] Example 2 Doxycycline enhances the antitumor effect of PD-1 inhibitors

[0061] Experimental method and steps:

[0062] 1. Establishment of B16-F10 melanoma and 4T1 breast cancer tumor models

[0063] Will 4*10 5 B16-F10 cells were subcutaneously injected into the right flank of C57BL / 6 mice to establish a subcutaneous model of B16-F10 tumor. Will 4*10 5 4T1 cells were injected into the fourth pair of mammary fat pads of BALB / C mice to establish a 4T1 orthotopic tumor model.

[0064] 2. Administration

[0065] The control group was only given normal saline; the PD-1 inhibitor group was intraperitoneally injected with PD-1 antibody (clone RMP1-14, Bio Xcell, 200 μg / injection) on days 11, 14, 18 and 21; the doxycycline group was given 50 mg Oral injection of doxycycline at a dose of / kg / day for 14 days.

[0066] 3. Record the tumor volume (length*width*width / 2) and the survival period of the mice.

[0067] Experimental results and evaluation

[0068] 1) if Figur...

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Abstract

The invention provides application of doxycycline in preparing a drug for inhibiting myeloid-derived suppressor cells. The doxycycline can serve as an inhibitor of the MDSC to inhibit the generation and recruitment activation of the body MDSC, increases the content of CD8T cells, and improves the immunosuppressive microenvironment of the body, thereby improving the immune regulation ability of thebody, so that the doxycycline is not only suitable for the preparation of anti-tumor drugs, but also suitable for the preparation of drugs for autoimmune diseases, infectious diseases, inflammatory-mediated tissue injuries and the like. In addition, the doxycycline can work synergistically with a PD-1(programmed cell death protein-1, programmed death-1) inhibitor, not only can enhance the anti-tumor effect of the PD-1 inhibitor, but also can prevent cytokine storms caused by programmed cell death protein-1(PD-1) inhibitor treatment.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, specifically, the application of doxycycline in the preparation of inhibitory drugs for myeloid-derived suppressor cells. Background technique [0002] Doxycycline (also known as doxycycline), belonging to the tetracycline class of antibiotics, is a well-known and widely used antibiotic. Tetracyclines mainly act on the 30S subunit of bacterial nucleosomes, interfere with the binding of amino acid tRNA to the action site on the 30S subunit, block the binding of aminoacyl tRNA to the ribosome-mRNA complex, inhibit protein synthesis, and also change The permeability of the cell membrane exposes important substances such as nucleotides in the cell, inhibits DNA synthesis, and thus achieves the antibacterial effect. Doxycycline is a type with stronger drug efficacy and wider application among tetracyclines (Adimora AA., 2002; Kovacova E, et al., 2002). About doxycycline is currently mainly used cl...

Claims

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Application Information

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IPC IPC(8): A61K31/65A61K45/06A61P29/00A61P35/00A61P31/04A61P37/04
CPCA61K31/65A61K45/06A61P29/00A61P31/04A61P35/00A61P37/04A61K2300/00
Inventor 杨诚孙涛周红刚刘慧娟刘艳荣高晶晶
Owner TIANJIN INT JOINT ACADEMY OF BIOTECH & MEDICINE
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