Genetically engineered human trophoblast cells, methods of making and using the same

By co-expressing mbIL-21, CD137L, and DLL1 in K562 cells, the JY511 cell line was constructed, which solved the problems of low expansion efficiency and poor functional maintenance of NK cells and γδ T cells in the existing technology, and achieved efficient expansion and safe cell therapy support, which is suitable for GMP and industrial production.

CN122128247BActive Publication Date: 2026-07-24HANGZHOU JIYUAN GENE TECH CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
HANGZHOU JIYUAN GENE TECH CO LTD
Filing Date
2026-04-30
Publication Date
2026-07-24

AI Technical Summary

Technical Problem

In existing technologies, K562-derived trophoblast cells have problems such as low expansion efficiency, poor functional maintenance, and cell phenotype depletion when expanding NK cells and γδ T cells, especially the Vδ1 subset. Furthermore, the construction of viral vectors faces GMP compatibility issues and safety risks.

Method used

Using the PiggyBac transposon system, three immunomodulatory factors, mbIL-21, CD137L, and DLL1, were stably co-expressed in K562 cells. The JY511 cell line was constructed, and the stemness maintenance of γδ T cells was enhanced through DLL1-Notch signaling, thereby achieving synergistic activation and efficient expansion of NK cells and γδ T cells.

Benefits of technology

It significantly improves the expansion efficiency and functional maintenance of NK cells and γδ T cells, avoids the potential risks of viral vectors, is suitable for GMP standards and industrial production, and provides a high-quality cell therapy support system.

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Abstract

The present application belongs to the field of cell therapy and immunotherapy, and provides a genetically engineered human trophoblast, a preparation method and application thereof. The human trophoblast takes K562 cells as starting cells, and stably expresses membrane-bound interleukin 21, CD137 ligand and Delta-like ligand 1 after genetic engineering. The constructed K562 three-factor trophoblast can significantly improve the expansion efficiency, activation state and functional stability of NK cells and γδT cells. The synergistic mechanism includes enhancing the proliferation, cytotoxicity and stemness maintenance of NK cells and γδT cells through STAT3, NF-κB and Notch signaling pathways, respectively. The human trophoblast has the advantages of good expression stability, significant functional enhancement, and high activity after freezing and recovery.
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Citation Information

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