Application of PLPP1 in preparation of T cell immune tumor related medicament

A PLPP1, 1.PLPP1 technology is applied in the direction of anti-tumor drugs, vaccines, intestinal cancer vaccines, etc., and can solve the problems affecting the response of T cells to blocking therapy and the effect of tumor therapy

Pending Publication Date: 2020-10-16
THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In theory, blocking antibody therapy targeting PD-L1 or PD-1 can improve tumor therapy, but in fact, clinical studies have shown that environmenta...

Method used

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  • Application of PLPP1 in preparation of T cell immune tumor related medicament
  • Application of PLPP1 in preparation of T cell immune tumor related medicament
  • Application of PLPP1 in preparation of T cell immune tumor related medicament

Examples

Experimental program
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specific Embodiment

[0032] The present application will be further explained below in conjunction with the accompanying drawings and embodiments. Before introducing the specific embodiments, the experimental background of some biological materials, experimental reagents, experimental equipment, etc. involved in the following embodiments is briefly introduced as follows.

[0033] biomaterials:

[0034] Peripheral blood from patients with esophageal cancer, lung cancer or colon cancer, as well as adjacent normal tissues and tumor tissues, were all obtained from relevant departments of the First Affiliated Hospital of Zhengzhou University after approval by the Ethics Committee; peripheral blood from healthy donors came from Zhengzhou City, Henan Province Red Cross Blood Center; lung cancer cell lines H460 and A549, from the Institute of Cells, Chinese Academy of Sciences; SPF grade CD45.1 C57BL / 6N wild-type female mice, from Peking University School of Basic Medicine; SPF grade CD45.2 OT-1 mice, An...

Embodiment 1

[0045] The inventor believes that the microenvironment of solid tumors is closely related to the function of T cells, and the formation of the microenvironment is the result of the joint action of T cells and tumor tissues. In order to explore and determine the tumor-related T cells in the tumor microenvironment The inventors conducted a series of experiments on the key influencing factors of metabolism, which are specifically introduced as follows.

[0046] (1) Differences in related expression molecules

[0047] In order to determine the actual difference in molecular expression, the inventors took samples of peripheral blood and tumor tissue from lung cancer patients, processed them into small fragments of 2-4 mm, treated them with three enzymes (enzyme H, enzyme R, enzyme A) and performed tissue digestion Finally, human peripheral blood mononuclear cells (PBMC) were extracted by density gradient centrifugation, CD8+ T cells were further separated by magnetic separation usi...

Embodiment 2

[0059] On the basis of Example 1, the inventors further used genetic engineering technology to knock down PLPP1 to study and analyze the influence of PLPP1 on the metabolism and function of activated CD8+ T cells. The specific research process is as follows.

[0060] (1) Flow cytometric analysis of functional molecular differences in CD8+ T cells with low and high expression of PLPP1

[0061] In Example 1, the existing database statistics have preliminarily shown that the expression of PLPP1 in CD8+ T cells is related to its function and metabolism. In order to further verify this association, the inventors used flow cytometry to detect PLPP1 in the tumor microenvironment of patients with lung cancer high and PLPP1 low Related factors in CD8+ T cells (for details, please refer to the existing technology for operation). The result is as figure 2 shown. Analysis can be seen: with PLPP1 low CD8+ T cells compared to PLPP1 high CD8+ T cells can secrete higher levels of kil...

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Abstract

The invention belongs to the technical field of cellular immune biology, and particularly relates to application of PLPP1 in preparation of a T cell immune tumor related medicament. The PLPP1 is a keyenzyme for regulating and controlling T cell phospholipid metabolism; in a tumor microenvironment, the reduction of the expression of the metabolism key enzyme PLPP1 causes abnormal CD8+ T cell phospholipid metabolism, then causes abnormal CD8+ T cell metabolism, and finally causes abnormal T cell functions; and that is, the expression of the PLPP1 has a positive correlation relationship with activation, infiltration and functions of CD8+ T cells in the tumor microenvironment. In-depth studies show that after a PDL1/ PD-1 signal path is activated, an AKT/ mTOR signal path is further activated, the expression of the T cell phospholipid metabolism key enzyme PLPP1 is regulated and controlled by a transcription factor GATA1, and finally the T cell function adjustment is achieved by the change of the T cell metabolism function.

Description

technical field [0001] This application belongs to the technical field of cellular immunology, and specifically relates to a patent application for the application of PLPP1 in the preparation of T cell immune tumor-related drugs. Background technique [0002] In recent years, in order to suppress the threat of malignant tumors to human health, chimeric antigen receptor T (chimeric antigen receptor T, CAR-T) cell therapy technology and immune checkpoint blockade antibody (immune checkpoint blockade, ICB) technology (ICB treatment mainly uses Lung cancer, esophageal cancer, gastric cancer, melanoma and other solid tumors) have developed rapidly, and have achieved certain success in the treatment of some types of blood and solid tumor patients, and improved the 5-year survival rate of patients. However, practical applications have shown that these T cell-based immunotherapy techniques are only effective in a small number of patients, especially in patients with solid tumors. ...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61P35/00
CPCA61K39/001163A61P35/00A61K2039/86A61K2039/836A61K2039/876A61K2039/80
Inventor 张毅平玉秦海名单吉琦
Owner THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIV
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