CXCR4 high-expression type iPSC-NK cell capable of enhancing bone marrow and tumor tissue homing ability, and preparation method and application of CXCR4 high-expression type iPSC-NK cell

By integrating the CXCR4 and membrane-bound IL-15/IL-15RA fusion protein genes into iPSCs, iPSC-NK cells with high CXCR4 expression were constructed, solving the problems of homing and survival of NK cells in tumor therapy. This achieved broad-spectrum anti-tumor effects in hematologic and solid tumors, and is GMP-compliant in production with low toxicity, making it suitable for large-scale allogeneic applications.

CN122104589APending Publication Date: 2026-05-29HANGZHOU JIYUAN GENE TECH CO LTD
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Patent Information

Application Number
CN202610591005.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-04-30
Publication Date
2026-05-29

AI Technical Summary

Technical Problem

Existing iPSC-derived NK cells have limitations in tumor treatment due to insufficient homing ability, limited in vivo survival, insufficient penetration into solid tumors, and difficulties in GMP-compliant production, which restrict their widespread application in hematologic malignancies and solid tumors.

Method used

By integrating the CXCR4 and membrane-bound IL-15/IL-15RA fusion protein genes into iPSCs using CRISPR/Cas9 gene editing technology, iPSC-NK cells with high CXCR4 expression were constructed, enhancing their homing ability in bone marrow and tumor tissues, and improving the in vivo survival and expansion capacity of NK cells through autocrine/paracrine activation loops.

Benefits of technology

It significantly improves the homing efficiency and in vivo survival of NK cells in tumor tissues, enhances their killing activity against solid tumors with high CXCL12 expression, achieves broad-spectrum anti-tumor effects in hematologic malignancies and solid tumors, and has GMP-compliant production and low toxicity, making it suitable for large-scale allogeneic applications.

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Abstract

The invention belongs to the technical field of biological medicine, and provides a CXCR4 high-expression type iPSC-NK cell capable of enhancing bone marrow and tumor tissue homing ability and a preparation method and application thereof. According to the cell, a pluripotent stem cell is taken as a starting cell, and a membrane binding type IL-15 and IL-15RA fusion protein gene and a CXCR4 receptor gene are over-expressed in the pluripotent stem cell; the pluripotent stem cells stably expressing the target gene are obtained, and then the iPSC-NK cells are obtained through induced differentiation. According to the invention, a membrane-bound IL-15 and IL-15RA fusion protein gene and a CXCR4 receptor gene are integrated to a safe port site of an induced pluripotent stem cell in a targeting manner through a gene editing technology, and an iPSC cell strain capable of stably expressing a key protein is constructed; the function-enhanced iNK cell is obtained through induced differentiation, and shows excellent bone marrow and various solid tumor tissue homing ability and lasting immune killing activity.
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