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Application of GSH combined with PD-1/PD-L1 blocking agent for promoting CD8+T cell functions

A PD-L1, PD-1 technology, applied in the field of immunotherapy combination therapy research

Pending Publication Date: 2021-07-06
THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

PD-1 / PD-L1 blockade combined with glutathione increases specific CD8 + The proliferative ability and function of T cells have not been reported

Method used

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  • Application of GSH combined with PD-1/PD-L1 blocking agent for promoting CD8+T cell functions
  • Application of GSH combined with PD-1/PD-L1 blocking agent for promoting CD8+T cell functions
  • Application of GSH combined with PD-1/PD-L1 blocking agent for promoting CD8+T cell functions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1, GSH combined with PD-1 / PD-L1 blocking agent on CD8 + Effects on T cell apoptosis, proliferation and function

[0035] 1. Isolation of peripheral blood mononuclear cells (PBMCs)

[0036] Specifically follow the steps below:

[0037] 1) Label 1-2 5mL negative pressure heparin anticoagulant tubes, draw 5-10mL peripheral venous blood from the patient, and store it at 4°C for a short time (<6 hours) or proceed directly to the next step.

[0038] 2) Serum separation by centrifuge: place blood collection tube in centrifuge for centrifugation, centrifugation conditions: 9ACC, 9DEC, 1500rpm / min, 10min.

[0039] 3) After the centrifugation, take out the blood collection tube, put it into the ultra-clean bench, light the alcohol lamp, and ventilate with positive pressure. Transfer the upper layer serum of the blood collection tube into a 4mL sterile centrifuge tube with a pipette gun and store it at -80°C. The lower layer of blood cells was transferred to a 50mL ster...

Embodiment 2

[0052] Effect of GSH on CD8 in chemotherapy patients + Effect of T cells and synergistic enhancement of MAGE-A3-specific CD8 in combination with PD-1 / PD-L1 blockade + Anti-tumor effect of T cells

[0053] 1. Experimental method: select chemotherapy and chemotherapy+GSH (1.8g / qd, ivgtt) two groups of patients, extract peripheral blood from patients before and after treatment, separate peripheral blood mononuclear cells (same as in Example 1), and use flow cytometry to detect peripheral PD-1 in blood + CD8 + Apoptotic ratio of T cells; and detected and compared the PD-1 of the two groups before and after chemotherapy + / PD-1 - CD8 + Levels of IFN-γ and TNF-α secreted by T cells. Animal experiments: HLA-A2 / MAGE-A3 co-positive EC109 was selected as target cells to establish a tumor-bearing mouse model, which was randomly divided into five groups with 5 nude mice in each group, (EC109 group, EC109+T cell therapy group, EC109+T cell therapy group+GSH, EC109+T cell therapy gro...

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Abstract

The invention belongs to the field of immunotherapy combined treatment research, and particularly relates to application of GSH combined with a PD-1 / PD-L1 blocking agent for promoting CD8+T cell functions. Specifically, the application is any one of the following four: 1) application in preparation of a product for promoting CD8+T cell proliferation; 2) application in preparation of a product for inhibiting CD8+T cell apoptosis; 3) application in preparation of a product for promoting CD8+T cell capability, wherein the function specifically refers to IFN-gamma secretion capability of cells; and 4) in preparation of drugs for treating diseases related to abnormal development of CD8+T cells. The invention provides a new thought for improving the anti-tumor function of in-vivo and in-vitro antigen specific T cells of tumor patients.

Description

technical field [0001] The invention belongs to the research field of combined immunotherapy, and specifically relates to the use of GSH combined with PD-1 / PD-L1 blockers to promote CD8 + Uses of T cell function. Background technique [0002] In the field of tumor immunotherapy, adoptive cell therapy and immune checkpoint inhibitors have entered the stage of tumor treatment. Among them, chimeric antigen receptor T cells (CAR-T), as an emerging adoptive immunotherapy, can significantly improve the prognosis of patients with B cell malignancies, but the treatment effect in solid tumors is poor , Immune checkpoint inhibitors represented by PD-1 monoclonal antibodies have been approved for a variety of malignant tumors, but some patients do not respond to treatment. The reason is that, on the one hand, there are factors in the tumor microenvironment that affect the activation and function of T cells; Sexual T cells are positively correlated with the survival of tumor patients...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/06A61K38/10A61P35/00
CPCA61K38/06A61K38/10A61P35/00A61K2300/00
Inventor 陈新峰张毅
Owner THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIV
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