MSLN-CAR-NK cells of an autocrine il2rβγ agonist and application thereof

By designing the autocrine IL2Rβγ agonist IL2Rβγ-A in NK cells and combining it with MSLN-CAR, the problem of insufficient activation of CAR-NK cells in the tumor microenvironment was solved, achieving a highly efficient killing effect on solid tumors and avoiding side effects caused by exogenous factors.

CN115124627BActive Publication Date: 2026-03-17THE NAVAL MEDICAL UNIV OF PLA
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2022-06-20
Publication Date
2026-03-17

AI Technical Summary

Technical Problem

Existing CAR-NK cell therapies have limited efficacy in treating solid tumors. The lack of immunosuppressive factors and cytokines in the tumor microenvironment limits their killing activity, and exogenous injection of cytokines may cause side effects and off-target activation.

Method used

We designed an autocrine IL2Rβγ-A specific agonist and bound it to a chimeric antigen receptor (MSLN-CAR) targeting the tumor antigen MSLN. By genetically modifying NK cells, we enabled them to autocrinely activate at the tumor site, provide cytokine signals, and enhance their killing activity.

Benefits of technology

It enhances the killing activity of CAR-NK cells, enabling large-scale expansion without the need for exogenous cytokine addition, significantly improving the therapeutic effect on MSLN-positive solid tumors such as pancreatic cancer and ovarian cancer, and avoiding the side effect of activating regulatory T cells.

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Abstract

This invention relates to the field of biomedical technology, specifically to a CAR-NK cell that secretes an IL2Rβγ agonist and targets the tumor antigen MSLN, and its application. The chimeric antigen receptor targeting MSLN is co-expressed in a polycistronic structure with IL2Rβγ-A in parallel. IL2Rβγ-A is an artificial polypeptide designed and synthesized by computer based on the conformation of IL2Rβγ. Its affinity for IL2Rβγ is significantly higher than that of natural IL-2; and it has no binding activity with IL-2Rα, avoiding the activation effect of natural cytokines on regulatory T cells, thereby significantly enhancing the killing activity of CAR-NK cells. This invention improves the in vitro and in vivo antitumor effect of MSLN-targeting CAR-NK cells and can be used for the treatment of MSLN-positive malignant tumors such as pancreatic cancer, ovarian cancer, and cervical cancer.
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Citation Information

Patent Citations

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  • Anti-human MSLN antibody and immune effector cell targeting MSLN

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