Dual-specific fusion protein antibody for treating intestinal cancer and application of dual-specific fusion protein antibody

Abstract

The invention discloses a dual-specific fusion protein antibody for treating intestinal cancer and application of the dual-specific fusion protein antibody. According to the dual-specific fusion protein antibody disclosed by the invention, one chain is an intestinal-cancer-specific antigen GUCY2C antibody and can be specifically conjugated with intestinal cancer cells, and the other chain is ULBP2(NKG2D ligand) and can be conjugated with a surface NKG2D activated acceptor of NKs. The dual-specific fusion protein antibody and the application thereof have the beneficial effects that by researching and developing the dual-specific antibody for the intestinal cancer, internal medicine treatment ways for late-stage difficult intestinal cancer will be extremely enriched, side reactions of drugsmay be greatly reduced, and the accuracy of treatment may be greatly improved; and the dual-specific fusion protein antibody disclosed by the invention can activate NK and position tumor cells, so that the tumor killing efficiency of the NK can be greatly increased, and treatment ways for the difficult intestinal cancer are enriched.

Description

[0001] (1) Technical field [0002] The invention relates to a bispecific fusion protein antibody for treating intestinal cancer and its application. [0003] (2) Background technology [0004] Natural killer cells (Natural Killer Cells, NK cells), as a kind of mononuclear cells in the blood, are the core component of human innate immunity, distributed in peripheral lymphoid organs and blood circulation system, and their main function is to participate in the body's innate It also plays an important role in immune regulation, and it can exert cytotoxic effect without antigen stimulation and activation; the target cells of NK cells mainly include: tumor cells, virus-infected cells, and some self-organized senescent cells and bacteria, parasites, etc. Therefore, NK cells are an important immune factor for the body's anti-tumor and anti-infection; in addition, NK cells are also involved in type II hypersensitivity reactions and inhibitory anti-host reactions. [0005] At present,...

AI Technical Summary

Problems solved by technology

[0008] The main challenge in the production of bispecific IgG antibodies is the correct connection of light and heavy chains. In the past, the most primitive way was to randomly synthesize asymmetric heterodimeric IgG antibodies from light and heavy chains, which easily produced a variety of unwanted by-products ;The use of the Knobs-into-holes (KiH) method has solved the correct connection of the heavy chain heterodimer, but the correct connection of the double antibody light chain has not been effectively solved; at this time, the CrossMAb technology came into being! This technology is based on the exchange of the Fab arm functional domains of bispecific IgG antibodies, which solves the problem of light chain connection, and the correct knot of heavy chain can be achieved by using KiH and electrostatic steering technology.

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