Anti-CD3 and anti-EpCAM bispecific antibody and application thereof in treating lung cancer

Abstract

The present invention discloses an anti-CD3 and anti-EpCAM bispecific antibody and an application thereof in treating lung cancer. The provided anti-CD3 and anti-EpCAM bispecific antibody is obtainedby connecting an anti-CD3 single-chain antibody and an anti-EpCAM single-chain antibody. The targeting and specific anti-CD3 and anti-EpCAM bispecific antibody is used as a bridge for binding of activated T cells and tumor cells to enhance an anti-tumor effect of effector T cells and body tumor immune response. Provided anti-CD3 and anti-EpCAM bispecific antibody molecular fragments can be constructed in vitro. The anti-CD3 single-chain antibody and the anti-Ep-CAM single-chain antibody are connected through a specific linker that does not affect action sites, and the anti-CD3 and anti-EpCAM bispecific antibody is high in binding sensitivity and large in affinity, and can bind two antigen epitopes simultaneously.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to an anti-CD3 and EpCAM bispecific antibody and its application in treating lung cancer. Background technique [0002] Lung cancer is one of the malignant tumors with the fastest increasing morbidity and mortality and the greatest threat to human health and life. In the past 50 years, many countries have reported that the morbidity and mortality of lung cancer have increased significantly. The incidence and mortality of lung cancer in men rank first among all malignant tumors, and the incidence and mortality of lung cancer occupy the second place in women. In the fight against lung cancer, people are constantly exploring new treatment methods. In 1961, Nisoneff and Rivers discovered bispecific antibody (bispecific antibody, BsAb). In recent years, due to the specificity and multifunctionality of bispecific antibody, it has gradually played an increasingly important role in...

AI Technical Summary

Problems solved by technology

[0005] In tumor immunotherapy methods, the tumor immune effects exerted by LAK cells, CIK cells, and NK cells are all broad-spectrum killing tumor cells, which is equivalent to using natural immunity to act on tumors, and the cell killing rate is very limited. The antigen cannot be eliminated; CAR-T can design a CAR structure for a specific antigen on the surface of the tumor, and can effectively kill the antigen-specific tumor cells, but the tumor killing effect in solid tumors is far inferior to that of hematological tumors, and it is easy to produce cells Factor storm, neurotoxicity, and treatment costs are very expensive; although TIL cells are very effective in killing tumor cells, they need to be isolated and purified from tumor tissues taken from patients during surgery. The culture period is long, the number and proliferation capacity of TIL cells are limited, and the operation is complicated , it is easy to miss the best treatment opportunity for patients; tumor vaccines and DC-CTLs are effective on tumor cells to a certain extent, but the low efficiency of DCs to effectively present tumor antigens is the biggest bottleneck. In addition, it is difficult and hard to obtain tumor neoantigens Large, which further limits its applicability; antibody therapy mainly uses the ability of antibodies to bind to antigens (including foreign and self), so as to effectively remove foreign substances invading the body. A protein that specifically binds to an antigen. Each antibody binds to a specific epitope. This combination can inactivate the antigen, and it may also be ineffective but sometimes cause pathological damage to the body, such as antinuclear antibodies, anti-double-chain The production of some autoantibodies such as DNA antibodies and anti-thyroglobulin antibodies can cause harm to the human body

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