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Immune cell and application thereof

A technology of immune cells and cells, applied in the field of biological cells, can solve problems such as low remission rate, off-target, and no good therapeutic effect on solid tumors, and achieve the effects of enhancing curative effect, enhancing stability, and enhancing anti-tumor ability

Pending Publication Date: 2021-08-13
SHENZHEN FIRST CONDOR BIOSCIENCE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although CAR-T cell therapy shines in the treatment of hematological tumors, it does not have a good therapeutic effect on solid tumors, with a low response rate and prone to off-target and other toxic side effects

Method used

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  • Immune cell and application thereof
  • Immune cell and application thereof
  • Immune cell and application thereof

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Experimental program
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Effect test

Embodiment 1

[0097] The preparation method and functional verification of the immune cells of the present embodiment include the following steps:

[0098] S100: Isolation of peripheral blood PBMC and culture of T cells.

[0099] Monocytes were isolated from donor peripheral blood, subjected to density gradient centrifugation using ficol, and enriched for T cells using a T cell sorting kit (CD3 MicroBeads, human-lyophilized, 130-097-043) using conjugated anti-CD3 / anti-CD28 magnetic beads to activate the culture and expansion of T cells; the medium used TexMACS GMP Medium (MiltenyiBiotec, 170-076-309), containing 10% FBS, 2mM L-glutamine, 100IU / ml rhIL2, all cells were placed at 37°C, 5% CO 2 Cultured in a constant temperature incubator to obtain T cells.

[0100] S200: cell line culture.

[0101] GPC3-expressing cell line: Huh7 (human hepatoma cells), purchased from ATCC.

[0102] Cell line that does not express GPC3: A549 (human non-small cell lung cancer cells), purchased from ATCC. ...

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Abstract

The invention relates to the technical field of biological cells, in particular to an immune cell and application thereof. A chimeric antigen receptor is expressed on the cytomembrane of the immune cell, and in addition, an immune checkpoint antibody protein fused with a cytokine receptor is also expressed on the cytomembrane. The expression CAR cell of the immune checkpoint antibody protein fused with the cytokine receptor is also expressed on the cytomembrane; through the immune checkpoint antibody protein which is fused with the cytokine receptor and is expressed on the immune cytomembrane, two negative feedback approaches PD-1 and CTLA-4 are blocked so as to weaken negative regulation and control of a tumor microenvironment for the immune cell, reduce exhaustion of the immune cell, enhance the tumor killing function of the immune cell and reduce inhibition of the immune cell by the tumor microenvironment; and in addition, through binding with the cytokine receptor, corresponding JAK and STAT signal channels are activated, and the cells are induced to secrete various active substances, including IFN-[gamma], perforin, granzyme and the like so as to inhibit growth of tumor cells, enhance an anti-tumor capacity, reduce the exhaustion and reduce the inhibition of the immune cell by the tumor microenvironment.

Description

technical field [0001] The invention relates to the technical field of biological cells, in particular to immune cells capable of membrane expression of immune checkpoint antibody proteins fused with cytokine receptors and CARs. Background technique [0002] In recent years, tumor immunotherapy has developed rapidly, especially adoptive cell therapy (ACT), which means that immune cells such as T cells and NK cells are isolated from patients, modified and expanded in vitro, and then reintroduced into patients for tumor treatment. method of treatment. In 2013, the immunotherapy of tumors was rated as the first among the "Top Ten Breakthroughs" by Science Impurities. [0003] CAR-T and TCR-T are important components of adoptive cell therapy, especially CAR-T therapy, which has made remarkable achievements in the treatment of blood tumors and achieved a high remission rate. A typical CAR structure consists of three parts Composition, extracellular recognition of tumor antigen ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/10A61K39/00A61P35/00
CPCC07K14/7051C07K16/2818C07K14/7155C07K16/2863C07K16/303C07K16/28A61K39/001119A61P35/00C07K2319/00C07K2319/02C07K2319/03C07K2319/33C07K2317/622
Inventor 马丽雅都小龙王乃会
Owner SHENZHEN FIRST CONDOR BIOSCIENCE CO LTD
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