High affinity anti-tumor nk cell and preparation method and application thereof

By designing high-affinity chimeric antigen receptor CAR-NK cells, utilizing haPD-1 to recognize PD-L1 ligands, and binding CD28 and DAP10 to activate signal transduction, the anti-tumor activity of NK92 cells is enhanced. This solves the problems of poor efficacy of CAR-T therapy in solid tumors and the inhibition of receptors in NK cell modification, achieving highly efficient tumor cell killing and allogeneic reinfusion.

CN116478931BActive Publication Date: 2026-06-02XINXIANG MEDICAL UNIV
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Patent Information

Application Number
CN202310550765.1
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-05-16
Publication Date
2026-06-02
Estimated Expiration
2043-05-16

AI Technical Summary

Technical Problem

Current CAR-T therapy is not effective in solid tumors, and has side effects such as cytokine storms and neurotoxicity. Furthermore, the process of modifying autologous T cells is complicated and expensive, while traditional NK cell modification involves killer inhibitory receptors that suppress immune function and cannot effectively recognize tumor cells.

Method used

We designed high-affinity chimeric antigen receptor (CAR-NK) cells, utilized the extracellular domain of haPD-1 to recognize the PD-L1 ligand, and bound the transmembrane domain of CD28 and the intracellular domain of DAP10. The activation signal was then transmitted through the intracellular domain of CD3ζ, thereby enhancing the antitumor activity of NK92 cells.

Benefits of technology

It enhances the anti-tumor immune activity and killing ability of NK92 cells, prolongs their survival time in vivo, reduces the risk of immunosuppression, and achieves highly efficient tumor cell killing, making it suitable for allogeneic reinfusion.

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Abstract

This invention belongs to the field of biotechnology, specifically relating to a high-affinity anti-tumor NK cell, its preparation method, and its application. This invention designs NK92 cells transfected with a haPD1 high-affinity chimeric conversion receptor, wherein the high-affinity chimeric conversion receptor includes the extracellular segment of haPD-1, the transmembrane segment of CD28, the intracellular segment of DAP10, and the intracellular segment of CD3ζ. This invention prepares haChR3-NK92 cells through the construction of a recombinant lentiviral vector, lentiviral packaging, and lentiviral transfection of NK92 cells. In this invention, haPD-1 serves as the extracellular recognition domain of the CAR structure, specifically binding to PD-L1 on tumor cells to achieve a stronger tumor-killing effect. The co-stimulatory molecule CD28 serves as the transmembrane region to transmit extracellular information into the cell, integrating the adaptor protein DAP10 of the NK cell surface activator receptor NKG2D into the cell, and further embedding the intracellular segment CD3ζ commonly used in CAR design to jointly promote NK cell activation. The preparation method of this invention can successfully construct haChR3-NK92 cells, achieve the expression of the target plasmid, and be applied in anti-tumor drug research.
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