CAR (Chimeric Antigen Receptor) carrier for killing gastric cancer cells by combining MSLN (Mesothelin) single-chain antibody and CCL19 (C-C-Motif Ligand 19) as well as constructing method and application thereof

Abstract

The invention belongs to the field of medical biology, and specifically relates to a CAR (Chimeric Antigen Receptor) carrier for killing gastric cancer cells by combining an MSLN (Mesothelin) single-chain antibody and a CCL19 (C-C-Motif Ligand 19) as well as a constructing method and application thereof. The CAR carrier comprises the MSLN single-chain antibody and a chemokine CCL19; a structure ofCAR is CD8leader-MSLN scFv-CD8alpha-CD28-CD137-CD3zeta-IRES-CCL19; T Cells containing the treatment carrier, i.e., CAR-T cells, are obtained through a virus infection mode; positive expression gastric cancer cells of MLSN can be targetedly identified and killed through expressing a CAR structure. The chemokine CCL19 is used for carrying out chemotaxis on T cell infiltrated tumor tissues, so thatstronger tumor cell killing ability can be expressed by the CAR-T cells.

Description

technical field [0001] The invention belongs to the field of medicine and biology, and specifically relates to a CAR vector combined with MSLN single-chain antibody and CCL19 to kill gastric cancer cells, its construction method and application. Background technique [0002] Gastric cancer is one of the most common malignant tumors in clinical practice in my country. It has the characteristics of high morbidity and high mortality. In my country, the incidence and mortality of gastric cancer occupy the third place among malignant tumors. At present, the treatment methods for gastric cancer mainly include surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Surgery is the only possible way to cure gastric cancer, but the simple surgical treatment of advanced gastric cancer may have residual lesions under the naked eye or under the microscope, which greatly increases the recurrence and metastasis rate; radiotherapy and chemotherapy are toxic and side effect...

AI Technical Summary

Problems solved by technology

Surgery is the only possible way to cure gastric cancer, but the simple surgical treatment of advanced gastric cancer may have residual lesions under the naked eye or under the microscope, which greatly increases the recurrence and metastasis rate; radiotherapy and chemotherapy are toxic and side effects, and the curative effect cannot achieve satisfactory results; therefore, the new Therapeutics are urgently needed

[0003] LAK cells, DCs, and CIK cells have all been used as immunotherapy methods for tumors, but all of the above treatments lack the ability to specifically recognize tumor associated antigen (TAA) and kill specific tumor target cells; while tumor immunoediting The process will reduce the expression of the main histocompatibility complex (MHC) on the surface of the target cell on the surface of the tumor cell, forming immune escape, so that the tumor cell can successfully evade the attack of T cells

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