A chimeric co-stimulatory switch receptor, encoding gene, recombinant expression vector, anti-tumor NK cell and its preparation method and application

Abstract

The invention relates to a chimeric co-stimulatory switching receptor, a coding gene, a recombinant expression vector, an anti-tumor NK cell and a preparation method and application thereof, belonging to the technical field of tumor immune cell therapy. The chimeric co-stimulatory switch receptor in the present invention consists of PD1 extracellular segment (1‑170aa), DAP10 extracellular, transmembrane and intracellular segment (19‑93aa) and costimulatory molecule 41BB intracellular segment (214‑255aa) , DAP10 does not contain signal peptides that will affect its transmembrane, but contains extracellular domains, which contain glycosylation sites, which can recruit free NKG2D and greatly enhance the activation of NK cells. According to the above-mentioned chimeric costimulatory switch receptor, its coding gene and recombinant expression vector can be obtained, and the recombinant expression vector can be transferred into NK cells to obtain anti-tumor NK cells, which have extremely high cytotoxicity.

Description

technical field [0001] The invention relates to a chimeric co-stimulatory switching receptor, a coding gene, a recombinant expression vector, an anti-tumor NK cell and a preparation method and application thereof, belonging to the technical field of tumor immune cell therapy. Background technique [0002] In recent years, tumor immune cell therapy has shined in tumor treatment due to its remarkable curative effect, especially T cells based on chimeric antigen receptor modification (CAR-T), which has shown great promise in the clinical treatment of hematological malignancies. Good targeting, lethality and persistence, it is the most convincing breakthrough in the field of tumor immunotherapy, opening a new door of hope for conquering tumors. Although the research and development of CAR-T technology has made continuous progress, it still faces many challenges. One of the main obstacles is that although CAR-T has a strong ability to kill cancer cells, the excessive immune resp...

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Problems solved by technology

[0005] The Chinese invention patent application with the application publication number CN107974433A discloses an enhanced anti-tumor NK cell, which is an NK cell modified by a dual-targeting chimeric receptor, and the dual-targeting chimeric receptor is derived from a PD1 cell The outer segment, the full-length segment of NKG2D, and the intracellular segment of the costimulatory molecule 41BB; when the anti-tumor NK cells are used to kill H1299 lung cancer cells, their cytotoxicity is low, which is only 3-4 times that of the parental NK92, which cannot meet the requirements. Treatment needs for solid tumors

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