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Application of artemisinin in targeted inhibition of myeloid-derived suppressor cells and preparation of tumor immunotherapy drugs

An immunotherapy drug and inhibitory cell technology, applied in the field of biomedicine, can solve problems such as artemisinin therapy combined with immunotherapy that have not been reported in research, and achieve the effect of less toxic side effects and promoting apoptosis.

Pending Publication Date: 2022-03-18
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although current studies have tried to use artemisinin to treat tumor diseases, there are no studies reporting artemisinin-targeted inhibition of myeloid-derived suppressor cell therapy and anti-PD-L1 antibody combination immunotherapy

Method used

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  • Application of artemisinin in targeted inhibition of myeloid-derived suppressor cells and preparation of tumor immunotherapy drugs
  • Application of artemisinin in targeted inhibition of myeloid-derived suppressor cells and preparation of tumor immunotherapy drugs
  • Application of artemisinin in targeted inhibition of myeloid-derived suppressor cells and preparation of tumor immunotherapy drugs

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Experimental program
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Effect test

Embodiment 1

[0022] (1) In vitro detection of the effect of artemisinin treatment on the aggregation and apoptosis of MDSCs

[0023] Freshly isolated bone marrow cells from C57BL / 6 mice were adjusted to a cell density of 1×10 with RPMI 1640 medium containing 10% FBS 6 / ml, 40ng / ml GM-CSF and 40ng / ml IL-6 were added accordingly. After thorough mixing, the cell mixture was plated in a 24-well plate and cultured at 37°C, 5% CO 2 in the incubator. ART (50 μM, 100 μM, 300 μM, 500 μM) was added to the third day of culture, and DMSO was used as the control group to detect the proportion and apoptosis of MDSCs by flow cytometry.

[0024] (2) In vitro detection of the effect of artemisinin treatment on releasing the inhibitory effect of MDSCs on T cells

[0025]The MDSCs isolated above were treated with 100 μM artemisinin for 12 hours, and Gr-1 was separated and purified by magnetic beads + cell. Spleen of C57BL / 6 mice was aseptically isolated and purified by flow cytometry to obtain spleen CD...

Embodiment 2

[0028] Analysis of transcriptome sequencing results showed that MDSCs inhibited the expression of M2-type pathway-related genes under the action of artemisinin compared with the control group DMSO. Western Blot and qRT-PCR were used to detect the expression of immunosuppressive factor gene ARG1 and M1 gene iNOS in MDSCs cells, and the levels of arginase and nitric oxide in MDSCs cells were detected by commercial kits.

[0029] figure 2 : Artemisinin can polarize MDSCs from M2-type tumor-promoting phenotype to M1-type anti-tumor phenotype.

[0030] Figures A-B: Transcriptome sequencing showed that under the action of artemisinin, compared with the control group DMSO, the ARG1 immunosuppressive gene of MDSCs was down-regulated, and the expression of related genes in the M2 pathway was inhibited. Figure C: qRT-PCR detection of the expression of M1-type macrophage marker genes and M2-type macrophage marker genes in MDSCs, the results showed that compared with the control group D...

Embodiment 3

[0032] Two tumor models, B16F10 and Hepa1-6, were established in C57BL / 6 mice to verify the effect of artemisinin on tumor growth in vivo, and combined with anti-PD-L1 antibody to enhance anti-PD-L1 immunotherapy.

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Abstract

The invention discloses application of artemisinin in targeted inhibition of myeloid-derived suppressor cells and in preparation of tumor immunotherapy drugs. A large number of experiments prove that artemisinin can inhibit aggregation of myeloid-derived suppressor cells, promote apoptosis of the myeloid-derived suppressor cells, inhibit the myeloid-derived suppressor cells in a targeted manner, relieve the immunosuppression effect of the myeloid-derived suppressor cells on effector T cells and reverse the tumor microenvironment immunosuppression state. The artemisinin is used as a drug for targeting myeloid-derived suppressor cells, and has the advantages of broad spectrum, effectiveness, small toxic and side effects, unsuitability for drug resistance, low cost and the like. The artemisinin has an important application prospect in the field of tumor immunotherapy drugs, and can be used for a combined immunotherapy for treating tumors, and the artemisinin and an anti-PD-L1 antibody immunotherapy are combined for application, so that a synergistic anti-tumor effect is realized.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the targeted inhibition of myeloid-derived suppressor cells by artemisinin and its application in the preparation of tumor immunotherapy drugs. Background technique [0002] Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment are a group of heterogeneous cells derived from myeloid progenitor cells and immature myeloid cells, which are dendritic cells, macrophages and granulocytes. precursor. There are a large number of MDSCs expansion in the blood, spleen and tumor tissues of tumor-bearing mice and the peripheral blood and tumor tissues of tumor patients. Mouse MDSCs were defined as cells that co-express Gr-1 and CD11b. According to the difference in expression of Gr-1 antigenic epitopes Ly6G and Ly6C, mouse MDSCs can be divided into granulocyte-like MDSCs (G-MDSCs, CD11b + Ly6G + Ly6C low ) and monocyte-like MDSCs (M-MDSCs, CD11b + Ly6G ...

Claims

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Application Information

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IPC IPC(8): A61K31/366A61K39/395A61P35/00A61P37/02
CPCA61K31/366A61K39/3955A61P35/00A61P37/02A61K2300/00
Inventor 万晓春鄢德洪张梦琪
Owner SHENZHEN INST OF ADVANCED TECH