Universal car-t cell and its preparation method and application

Abstract

The invention belongs to the field of immunotherapy, and relates to a universal CAR-T cell and its preparation method and application. In the universal CAR T cell of the present invention, the functions of T cell antigen receptor (TCR) and major histocompatibility complex (MHC Ⅰ, MHC Ⅱ) in T cells are simultaneously inhibited through multiple gene knockout; The genes of the TCR include TRAC and / or TRBC; the genes encoding the major histocompatibility complex include HLA-A, B2MH and CIITA. The universal CAR-T cells of the present invention can target specific tumor-associated markers and inactivate TCR and MHC functions on the cell surface, which can reduce immune rejection caused by allogeneic cell therapy and safely and effectively eliminate tumor cells in patients. And it is not affected by the patient's own condition or treatment method during use, and can be prepared at any time, and treatment can be given at the best time to ensure the effectiveness of treatment.

Description

technical field [0001] The invention belongs to the field of immunotherapy, and relates to a general-purpose CAR-T cell and its preparation method and application, in particular to a general-purpose T cell, a general-purpose CAR-T cell, its preparation method and its application in medicine. Background technique [0002] Adoptive cell therapy (ACT) is a kind of biotherapy technology, which expands autologous immune cells (mainly T cells) in vitro, and then reintroduces them to tumor patients to achieve therapeutic purposes. It is the fourth treatment after surgery, radiotherapy and chemotherapy, and it is widely used in clinical treatment. [0003] Chimeric antigen receptor, also known as CAR, is an artificial receptor that mimics the function of TCR. When the antigen (receptor) on the surface of the tumor cell binds to the antibody (ligand) of the chimeric antigen receptor, the signal is transmitted into the cell through the hinge region and the transmembrane region, and t...

AI Technical Summary

Problems solved by technology

However, most patients, especially tumor patients, have undergone other treatments before CAR-T cell adoptive therapy, such as chemotherapy and radiotherapy, which leads to less T lymphocytes acquired, and even many patients due to the effect of drugs It is difficult to expand the T cells in vitro, and the T cells from the patient's own source may also have functional attenuation or loss, and it is more difficult to genetically modify T cells, and the therapeutic effect and safety are not easy to control. These obstacles all affect CAT-T Application promotion and development of cell therapy and tumor clinical treatment

[0005] Allogeneic cells refer to cells belonging to the same species but genetically different individuals; although more T lymphocytes can be isolated from the peripheral blood of healthy people, the positive rate of CAR infection is high, and their vitality and function are better than those of patient-derived T lymphocytes. However, allogeneic cell therapy still faces many obstacles: due to the immunogenetic differences between the donor and the recipient, on the one hand, the T lymphocytes of the immunocompetent donor are entering the recipient After the patient has proliferated to a certain extent, the normal cells or tissues of the recipient patient are mistaken for the target to attack, resulting in graft-versus-host response (GVHD). On the other hand, the normal immune system in the recipient as an allogeneic cell may also It will be cleared to produce host-versus-graft reaction (HVGR), which will affect the therapeutic effect

For HVGR, immunosuppressive drugs are mainly used to suppress the activity of the recipient's immune system before treatment, but immunosuppressive drugs will affect the efficacy of reinfused cells during adoptive cell therapy; for GVHD, HLA matching is mainly used for prevention , but the success rate of HLA matching is low, time-consuming and expensive

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