Bispecific fusion protein antibody for the treatment of intestinal cancer and its application

Abstract

The invention discloses a bispecific fusion protein antibody for treating intestinal cancer and application thereof. One chain of the bispecific fusion protein antibody of the present invention is an intestinal cancer-specific antigen GUCY2C antibody, which can specifically bind to intestinal cancer cells, and the other chain is ULBP2 (NKG2D ligand), which can bind to NKG2D activation receptors on the surface of NKs. The beneficial effects of the present invention are mainly reflected in: the research and development of the bispecific antibody for intestinal cancer by the present invention will greatly enrich the medical treatment methods for advanced refractory intestinal cancer, and may greatly reduce the side effects of drugs and the accuracy of treatment. The bispecific fusion protein antibody of the present invention can activate NK and localize it to tumor cells, so that the tumor killing efficiency of NK is greatly improved, and the treatment methods for refractory intestinal cancer are enriched.

Description

(1) Technical field [0001] The invention relates to a bispecific fusion protein antibody for treating intestinal cancer and its application. (2) Background technology [0002] 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. [0003] At present, the research o...

AI Technical Summary

Problems solved by technology

[0006] 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 method was to randomly synthesize asymmetric heterodimeric IgG antibodies from light and heavy chains, which is prone to produce a variety of unwanted by-products ; The use of Knobs-into-holes (KiH) method has solved the correct connection of heavy chain heterodimers, but the correct connection of double antibody light chain has not been effectively solved; at this time, 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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