CAR carrier for killing gastric cancer cells by combining MSLN single chain antibody and PD-1mAb, construction method and application thereof

Abstract

The invention belongs to the field of medical biology, and particularly relates to a CAR carrier for killing gastric cancer cells by combining an MSLN single-chain antibody and PD-1 mAb, and a construction method and application thereof. The CAR carrier comprises an MSLN single-chain antibody and PD-1 mAb, and the CAR structure is CD8 leader-MSLNscfv-CD8 alpha-CD137-CD3 zeta-IRES-PD-1 mAb, CAR-T cells are obtained through virus infection, and the gastric cancer cells of positive expression of MSLN are identified and killed by expressing the CAR structure. PD-1 mAb binds to PD-1 on the surfaceof T cells and blocks the binding of PD-1 and PD-L1, so that the growth and proliferation of T cells are upregulated, and CAR-T cells show stronger tumor cell killing ability.

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 PD-1 mAb 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 eff...

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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