Anti-tumor pharmaceutical composition based on macrophage effect blocking and application thereof

A technology of anti-tumor drugs and macrophages, which is applied in the field of anti-tumor drug compositions, can solve the problems affecting the function of tumor-infiltrating macrophages, which are not clear, and achieve the restoration of anti-tumor immune response, good tumor growth, and inhibition of tumor growth Effect

Inactive Publication Date: 2019-07-12
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is unclear whether epigenetic therapy affects the function of tumor-infiltrating macrophages

Method used

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  • Anti-tumor pharmaceutical composition based on macrophage effect blocking and application thereof
  • Anti-tumor pharmaceutical composition based on macrophage effect blocking and application thereof
  • Anti-tumor pharmaceutical composition based on macrophage effect blocking and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] The effect of epigenetic therapy on tumor growth and anti-tumor T cell immune response was studied by mouse tumorigenesis experiment.

[0053] The above mouse experiments were set up with a negative control group and an experimental group. The mice in the negative control group were treated with intraperitoneal injection of PBS, and the mice in the experimental group were treated with intraperitoneal injection of the epigenetic inhibitor GSK126+5-AZA-dC. The mouse strain used in the above tumor formation experiment was C57BL / 6, and the tumor cell line used was the mouse hepatoma cell line Hepa1-6.

[0054] Such as figure 1 Shown is the effect of epigenetic therapy on tumor growth and immune cells in tumor-bearing mice. figure 1 A is the statistical diagram of the effect of epigenetic therapy on tumor size; figure 1 B is a statistical diagram of the effect of epigenetic therapy on the number of cytotoxic T cells in the tumor; figure 1 C is a statistical diagram of th...

Embodiment 2

[0057] The effects of epigenetic therapy on macrophage function in tumors were investigated by tumorigenesis in mice.

[0058] The above mouse experiments were set up with a negative control group and an experimental group. The treatment was the same as in Example 1. The mice in the negative control group were treated with intraperitoneal injection of PBS, and the mice in the experimental group were treated with intraperitoneal injection of the epigenetic inhibitor GSK126+5-AZA-dC. The mouse strain used in the above tumor formation experiment was C57BL / 6, and the tumor cell line used was the mouse hepatoma cell line Hepa1-6.

[0059] Such as figure 2 Shown is the effect of epigenetic therapy on the tumor-promoting phenotype of macrophages. The picture shows the statistical diagram of the effect of epigenetic therapy on the expression of tumor-promoting molecules CCL20 (scya20 gene), IL-6 and IL-10 in macrophages in tumor-bearing mice. figure 2 In the study, after the trea...

Embodiment 3

[0062] The effect of the combination drug composition on tumor growth and anti-tumor T cell immune response was studied by mouse tumor formation experiment.

[0063] The mouse experiment above was set up as a control group and an experimental group. The mice in the control group were given intraperitoneal injection of PBS, or the epigenetic inhibitor GSK126+5-AZA-dC alone, or the macrophage-specific clearance antibody (αCSF1R antibody), and the mice in the experimental group were given intraperitoneal injection Joint composition treatment. The mouse strain used in the above tumor formation experiment was C57BL / 6, and the tumor cell line used was the mouse hepatoma cell line Hepa1-6.

[0064] Such as image 3 Shown is the effect of combined drug composition treatment on tumor growth and anti-tumor T cell immune response in tumor-bearing mice. image 3 A is a statistical diagram of the influence of the composition treatment on the infiltration quantity of cytotoxic T cells in...

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Abstract

The invention provides an anti-tumor pharmaceutical composition based on blocking macrophage effects and application thereof, and illuminates the biological mechanism of the anti-tumor pharmaceuticalcomposition in the tumor treatment process. The anti-tumor pharmaceutical composition based on macrophage effect blocking comprises an epigenetic inhibitor and a macrophage effect blocker. The drug can effectively recover anti-tumor immune response of T cells, and better inhibits the growth of tumor. Because the macrophage effects are blocked, the negative feedback effects brought by the epigenetic inhibitor are cleared away, the epigenetic inhibitor and the macrophage effect blocker are combined to generate a synergistic effect, and therefore, the drug has a good clinical application prospect.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to an antitumor pharmaceutical composition based on blocking the effect of macrophages and its application. Background technique [0002] Primary hepatocellular carcinoma (Hepatocellular carcinoma, HCC) is one of the most common malignant tumors in the world, and its morbidity and mortality are among the highest in various malignant tumors. China is a high-incidence area for liver cancer, accounting for 55% of the total number of HCC patients in the world. The treatment of early liver cancer is based on radical resection. However, the 5-year survival rate is only 50% for patients who have undergone surgical treatment in the early stage of liver cancer; and there is no effective treatment for patients with advanced liver cancer. Therefore, seeking new treatment methods for liver cancer is an urgent medical problem to be solved. [0003] Epigenetic silencing, including methylat...

Claims

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Application Information

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IPC IPC(8): A61K31/496A61K31/5377A61K31/706A61K31/4184A61K31/7072A61K31/708A61P35/00
CPCA61K31/4184A61K31/496A61K31/5377A61K31/706A61K31/7072A61K31/708A61P35/00A61K2300/00
Inventor 邝栋明魏瑗
Owner SUN YAT SEN UNIV
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