Alpha1beta1 integrin-dependent enhanced CAR (chimeric antigen receptor) macrophage as well as preparation method and application thereof

Abstract

The invention discloses an alpha1beta1 integrin-dependent enhanced CAR (chimeric antigen receptor) macrophage as well as a preparation method and application thereof, and belongs to the fields of immunology and tumor therapeutics. The CAR macrophage comprises an alpha 1 beta 1 integrin transmembrane region, an intracellular signal regulation motif, an Fc gamma R I intracellular signal transduction motif and an extracellular antigen binding region, and nucleotide sequences are respectively shown as SEQ ID NO: 1-4. According to the invention, CAR macrophages are constructed on the basis of an alpha 1 beta 1 integrin mediated Fc gamma R I intracellular signal transduction domain, and tests prove that the CAR macrophages activate macrophage activation signals, promote the phagocytic ability of the macrophages and synergistically enhance the anti-tumor effect. By designing the specific element suitable for the macrophage signal transduction function, a real CAR macrophage technology platform is constructed, and the CAR macrophage is widely applied to various CAR macrophages to treat solid tumors in the future and designed in an extension mode.

Description

technical field [0001] The present invention relates to the technical fields of immunology and tumor therapy, in particular to an α1β1 integrin-dependent enhanced CAR macrophage and its preparation method and application. Background technique [0002] Immunotherapy plays an important role in the field of tumor treatment, and has continuously made important progress. In recent years, CAR-T cell therapy has been approved by the US FDA and my country's drug regulatory department as a clinical drug for the treatment of specific blood cancers because of its good curative effect in the field of hematological tumors. However, CAR-T cell therapy is difficult to infiltrate solid tumors by T cells, and T cells encounter immune failure in the tumor microenvironment. So far, CAR-T cell therapy has made slow progress in the treatment of malignant solid tumors. At present, exploring more types of immune cells for the development of adoptive cell therapy to carry out specific and effecti...

AI Technical Summary

Problems solved by technology

Unfortunately, after macrophages are recruited into tumor tissue, in order to avoid immune attack by macrophages, the tumor microenvironment mostly low-expresses immune-inducing factors such as IFN-γ, which prevents the formation of M1-type polarized macrophages. and the effective activation of anti-cancer activation properties, which objectively promote the malignant progression of solid tumors

[0006] In recent years, although many researchers have conducted research on the construction of macrophages, due to inhibitory factors such as low expression of IFN-γ in the tumor microenvironment, the ability of macrophages to clear tumor cells such as innate immune phagocytosis has been significantly inhibited, and There is no real successful construction of CAR-M, but how to design the specific elements of CAR-M signal transduction function to be more suitable for the anti-cancer potential mechanism of CAR-M itself, so as to form a real CAR-M technology system is an urgent problem to be solved

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