Engineered immune cell with adjustable target gene as well as preparation method and application of engineered immune cell

Abstract

The invention discloses a target gene adjustable engineering immune cell and a preparation method and application thereof, the cell comprises a target cell and an immune cell, the target gene of the immune cell is inserted in the TCR response gene position of the target cell, and the TCR response gene and the target gene share the same promoter; the TCR response gene comprises one of IFN (interferon)-gamma, PD-1 (programmed death-1), IL-2 (interleukin-2), 4-1BB (bovine B), TIM3 (trimester-like motif 3) and CTLA-4 (cytotoxic T lymphocyte The target gene comprises one of an IL-15 gene, an IL-12 gene, an IL-18 gene, an IL-21 gene, an IL-7 gene, an IL-23 gene and a CCL19 gene. The engineered immune cell can stimulate a downstream pathway, so that any gene in TCR response genes IFN-gamma, PD-1, IL-2, 4-1BB, TIM3 and CTLA-4 is activated, and high expression is realized, as the target gene and the TCR response gene share the same promoter, the target gene is expressed, the killing effect of the immune cell is enhanced, and the safety is improved; when the target cells are not stimulated, the target genes cannot be expressed, so that the expression of the target genes is regulated and controlled.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to an engineered immune cell whose target gene can be regulated and a preparation method and application thereof. Background technique [0002] At present, immune cell therapy of tumors has become the fourth method of tumor treatment in addition to surgery, radiotherapy and chemotherapy, and will become the necessary method of tumor treatment in the future. Immune cell therapy is to collect peripheral venous blood of patients, isolate peripheral blood mononuclear cells in a GMP laboratory, and under the induction of various cytokines, a large number of immune effector cells with high anti-tumor activity are amplified, and then intravenously and intradermally. Injection, intervention, etc. are returned to the patient to achieve the purpose of enhancing the patient's immune function and killing tumor cells. Commonly used immune cell therapy methods include TCR-T, NK, CAR-T, CIK, DC, TIL, ...

AI Technical Summary

Problems solved by technology

[0006] The inducible expression systems widely used at present are to integrate simplified endogenous promoters, such as NFAT-IL2mini promoter system, into viral vectors, and then deliver them into cells. In fact, the expression of endogenous genes is an extremely complex process. The regulatory process of the promoter often includes several thousand or even longer DNA base sequences, and the epigenetic regulation of the genome, trans-regulation and high-level chromosome structure will affect the expression of the target gene, so the existing expression system has many shortcomings. Far from achieving precise expression of the target gene

Images