Chimeric antigen receptor containing CD3 epsilon intracellular region with Y/F mutation and application of chimeric antigen receptor

Abstract

The invention provides a chimeric antigen receptor containing a CD3 epsilon intracellular region with Y / F mutation. The chimeric antigen receptor comprises an extracellular domain, a transmembrane domain and an intracellular domain which are connected in sequence; one end, connected with the transmembrane domain, of the intracellular domain is connected with a CD3 epsilon intracellular region with Y / F mutation, and the CD3 epsilon intracellular region with Y / F mutation refers to a Y / F mutant CD3 epsilon intracellular region in which two tyrosine in the CD3 epsilon intracellular region ITAM are mutated into amphetamic acid. The persistence of the T cells can be remarkably improved by improving the survival ability, lowering the apoptosis level and improving the proliferation ability of the T cells modified by the chimeric antigen receptor, so that the anti-tumor ability of the T cells is remarkably improved. In clinical application, the tumor treatment effect can be further improved, the disease relieving time is prolonged, the recurrence rate is reduced, and the lifetime of a patient is prolonged. Meanwhile, the T cells modified by the chimeric antigen receptor can down-regulate the levels of expression cell factors IFN-gamma and TNF-alpha, and inflammatory cell factors such as IL-1beta and IL-6 generated by activation of macrophage monocytes are reduced.

Description

technical field [0001] The invention relates to the field of chimeric antigen receptors, in particular to a chimeric antigen receptor comprising a CD3ε intracellular region with a Y / F mutation and its use. Background technique [0002] Chimeric antigen receptor is referred to as CAR (chimeric antigen receptor), and T cells equipped with CARs targeting specific tumor antigens are called CAR-T cells. CAR-T therapy is widely used in the treatment of tumors, especially the immunotherapy of solid tumors. It is a new type of precise targeted therapy for the treatment of tumors. In recent years, through optimization and improvement, it has achieved good results in clinical tumor treatment. A very promising new tumor immunotherapy method that is accurate, fast, efficient, and has the potential to cure cancer. [0003] However, CAR-T therapy still has many limitations, such as cytokine storm, neurotoxicity safety, and poor sustainable proliferation ability encountered in the clinica...

AI Technical Summary

Problems solved by technology

These two studies have shown that the continuous proliferation and survival ability of 28Z CAR-T cells is relatively poor, and the efficacy needs to be improved

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