Cell membrane-expressed il-15 fusion protein and use thereof in cell therapy

By expressing the IL-15 fusion protein on the immune cell membrane, the difficulties in target selection and tumor microenvironment inhibition of existing CAR-T, CAR-NK and CAR-γδT cell therapies have been solved, achieving efficient killing of tumor cells and enhancement of immune cell function.

WO2026124408A1 Publication Date: 2026-06-18JILIN UNIV FIRST HOSPITAL
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Patent Information

Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
JILIN UNIV FIRST HOSPITAL
Filing Date
2025-12-08
Publication Date
2026-06-18

AI Technical Summary

⚠Technical Problem

Existing CAR-T, CAR-NK, and CAR-γδT cell therapies for cancer treatment face challenges such as difficulty in target selection, high manufacturing costs, and inhibition of the tumor microenvironment, resulting in poor treatment efficacy and high risk of side effects.

⚗Method used

Design a cell membrane-expressed IL-15 fusion protein, including IL-15, IL-15Rα signal peptide, IL-15Rα, and a transmembrane region. By linking it with a chimeric antigen receptor (CAR), modify immune cells to achieve efficient expression of IL-15 on the cell membrane, thereby enhancing the killing ability and persistence of immune cells.

🎯Benefits of technology

It achieved highly efficient killing of tumor cells by immune cells, enhanced the proliferation capacity and IFN-γ expression level of immune cells, altered the tumor microenvironment, and reduced the risk of cytokine release syndrome.

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Abstract

Provided are a cell membrane-expressed IL-15 fusion protein and a use thereof in cell therapy. The provided fusion protein comprises an IL-15Rα signal peptide, IL-15, an IL-15Rα sushi domain, and a transmembrane region; and a cell modified with the fusion protein can achieve efficient expression of IL-15 on the surface of a cell membrane, can effectively avoid side effects caused by the secretion and expression of IL-15, and is safe and controllable. An immune cell modified with a chimeric antigen receptor containing the membrane-expressed IL-15 fusion protein has a stronger tumor killing function, higher IFN-γ secretion, and a greater proliferative capacity; after treatment with lactic acid and TGF-β which are abundant in a tumor microenvironment, the immune cell retain a strong tumor killing function; and the immune cell can activate the anti-tumor function of immune cells other than the immune cell. The constructed immune cell can improve the therapeutic effect against tumors, prolong the duration of disease remission, and improve overall survival in patients.
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