Chimeric antigen receptor T cell and application thereof

Abstract

The invention provides a chimeric antigen receptor T cell and application thereof. The chimeric antigen receptor T cell expresses a chimeric antigen receptor of a specific binding antigen, IL-7 and CCL19; signal peptide of the IL-7 is signal peptide of T cell secretion protein; and a promoter of the CCL19 is an NFAT regulation promoter. According to the chimeric antigen receptor T cell and the application thereof provided by the invention, the IL-7 and the CCL19 are optimized, the signal peptide of the IL-7 is changed, the continuous secretion of the CCL19 is changed to be conditioned secretion, the built CAR-T cell can continuously secrete the IL-7 to the outside of the cell, the secreted CCL19 is expressed after a tumor antigen is recognized, and immune cells are maximally recruited inside a tumor, so that an anti-tumor effect of the CAR-T cell is remarkably improved.

Description

technical field [0001] The invention belongs to the field of tumor cell immunotherapy, relates to a chimeric antigen receptor T cell and its application, in particular to a chimeric antigen receptor T cell stably expressing cytokines and deactivating factors at a high level and its preparation Application in antitumor therapeutic drugs. Background technique [0002] Chimeric antigen receptor T cell (CAR-T) immunotherapy is to induce T cell activation by expressing a chimeric antigen receptor molecule that specifically recognizes and binds to tumor antigens on the T cell membrane, thereby achieving A technique for specific killing of tumor cells. [0003] At present, CAR-T immunotherapy has made a huge breakthrough in the field of leukemia treatment. The US FDA has approved two CD19-targeting CAR-T cell products for marketing, and many domestic companies have also carried out clinical trials targeting CD19. [0004] Although CAR-T technology has made some breakthroughs in t...

AI Technical Summary

Problems solved by technology

Although the exogenous introduction of IL-7 can make T cells transcribe and translate IL-7 protein, the secretion of IL-7 protein to the extracellular space is still strictly controlled by T cells. The research reported by Adachi et al. shows that exogenous IL-7 protein cannot be secreted. to the problem of T cells

[0007] CN109504660A discloses a fourth-generation CAR-T cell and its construction method and application. The CAR includes an extracellular antigen binding region, a hinge region, an intracellular signal transduction region, and a cytokine signal region, wherein the extracellular antigen The binding region targets the two spatial epitopes of the Nectin-4 antigen, and the cytokine signaling region is IL7 and CCL19. However, exogenous IL-7 protein cannot be secreted outside T cells, and the continuous secretion of CCL19 cannot be maximized. The problem with recruiting peripheral blood immune cells into tumor interiors

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