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Anti-tumor drug composition based on immune checkpoint blockage and application thereof

A technology of immune checkpoints and anti-tumor drugs, which is applied in the field of biomedicine, can solve the problems of not being able to predict the improvement of treatment effect and low clinical response, and achieve the effect of improving treatment effect and inhibiting tumor growth

Inactive Publication Date: 2019-07-09
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, clinical responses to PD-1 / PD-L1 mAbs remain very low in cancer patients with PD-L1-positive features
Tip: The expression of PD-L1 may represent a more complex immune signature in tumors, which cannot predict the improvement of treatment effect well

Method used

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  • Anti-tumor drug composition based on immune checkpoint blockage and application thereof
  • Anti-tumor drug composition based on immune checkpoint blockage and application thereof
  • Anti-tumor drug composition based on immune checkpoint blockage and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] The local immune characteristics reflected by the expression of PD-L1 were studied by human tumor tissue detection.

[0066] The above experiments were divided into two groups with high expression and low expression according to the expression of PD-L1 in the samples. Using the PD-L1 low expression group as a control, explore the CD3 expression in the PD-L1 high expression group + T cells and CD68 + Infiltration of macrophages.

[0067] figure 1 PD-L1 expression in tumor samples and local CD3 + T cells and CD68 + relationship with macrophage infiltration. figure 1 In the four tumors of liver cancer (HCC), colon cancer (COAD), gastric cancer (STAD) and lung cancer (LUAD), the CD3 + T cells and CD68 + Statistical graph of macrophage count. The results showed that in liver cancer (HCC), intestinal cancer (COAD), gastric cancer (STAD) and lung cancer (LUAD), CD3 in tissue samples with high expression of PD-L1 + T cells and CD68 + The infiltration number of macroph...

Embodiment 2

[0070] The relationship between the immune status reflected by PD-L1 and the prognosis of patients was studied by human tumor tissue detection.

[0071] The above experiments were divided into two groups with high expression and low expression according to the expression of PD-L1 in the samples, and the difference in the recurrence of patients in the two groups was compared. Select the samples with high expression of PD-L1, further according to CD68 + Macrophage / CD3 + The proportion of T cells divides the samples into two groups or four groups, and compares the difference in the recurrence of patients between different groups.

[0072] figure 2 It is the relationship between the expression of PD-L1, CD3 and CD68 in tumor samples and the recurrence of patients. figure 2 In the four tumors of liver cancer (HCC), colon cancer (COAD), gastric cancer (STAD) and lung cancer (LUAD), the statistical chart of recurrence between patients with high expression of PD-L1 and patients w...

Embodiment 3

[0075] To study the effect of tumor macrophages on tumor malignant biological behavior by in vitro experiments.

[0076] Experiment A: detection of changes in migration ability of tumor cells treated with macrophage supernatant (Tumor associated macrophage cultured medium, referred to as TAM-CM in the present invention). The experiment set up a negative control group and an experimental group. The tumor cells in the negative control group were not treated, and the tumor cells in the experimental group were treated with macrophage supernatant.

[0077] Experiment B: To detect the effect of tumor macrophage supernatant on tumor migration ability under the condition of inhibiting NF-κB signaling pathway of tumor cells or silencing tumor cell NF-κB subunit P65. The experiment set up a negative control group and an experimental group. The tumor cells in the negative control group were not treated, treated with DMSO (Dimethyl Sulfoxide, a solvent for P65 inhibitors) or transfected...

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Abstract

The invention provides an anti-tumor drug composition based on immune checkpoint blockage and application thereof. The biological mechanism of the composition in the tumor treatment process is demonstrated. The anti-tumor drug composition comprises an immune checkpoint inhibitor and a macrophage reaction blocker. The anti-tumor drug composition is good in anti-tumor effect; since the immune checkpoint inhibitor and the macrophage reaction blocker remove two different tumor promoting factors respectively, a synergistic effect is realized through the combination of the immune checkpoint inhibitor and the macrophage reaction blocker, and the tumor growth can be more effectively restrained. Thus, the drug composition has broad clinical application prospects.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to an anti-tumor pharmaceutical composition based on immune checkpoint blockade and its application. Background technique [0002] Cancer (malignant tumor) has become a global public health problem, especially in our country. The Ministry of Health reported that the cancer death rate among urban and rural residents in China has increased by more than 80% in the past 30 years. At present, cancer has become the first cause of death of urban residents and the second cause of death of rural residents in China. Although the diagnosis and treatment of tumors have made significant progress with the advancement of medicine, the mortality rate of malignant tumors remains high, and seeking new treatments is still a medical problem to be solved urgently. [0003] The most common treatments for cancer in the past have included surgical resection, chemotherapy, and chemotherapy. However, ...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K39/395A61P35/00
CPCA61K39/395A61K45/00A61P35/00A61K2300/00
Inventor 魏瑗邝栋明
Owner SUN YAT SEN UNIV