長期的ながん免疫療法のためのCAR-NK前駆細胞療法を開発(Researchers Developed CAR-NK Progenitor Cell Therapy for Long-Lasting Cancer Immunotherapy)

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2026-03-04 中国科学院(CAS)

中国科学院(CAS)動物研究所の研究チームは、長期間持続するがん免疫療法を実現する新しいCAR-NK前駆細胞(CAR-iNKP)療法を開発した。従来のCAR-NK細胞療法は安全性が高い一方、体内での増殖や持続性が限られ、複数回投与が必要になる課題があった。研究ではヒト多能性幹細胞(PSC)からNK前駆細胞様のiNKP細胞を作製し、CXCR4遺伝子を導入して骨髄ニッチへの移行能力を強化した。マウスモデルに低用量で投与すると、細胞は骨髄に定着して7~10日で機能的NK細胞へ分化し、80日以上体内で持続した。CD19およびCD7を標的とするCAR-iNKPは白血病モデルで腫瘍再発を防ぎ、化学療法と併用すると長期完全寛解を達成した。従来のCAR-NKより持続性と治療効果が高く、残存腫瘍の除去や再発防止に有望ながん免疫療法として期待されている。

長期的ながん免疫療法のためのCAR-NK前駆細胞療法を開発(Researchers Developed CAR-NK Progenitor Cell Therapy for Long-Lasting Cancer Immunotherapy)
Schematic of CAR-iNKP Cell Therapy. (Image by WANG Jinyong’s team)

<関連情報>

多能性幹細胞由来CAR-NK前駆細胞療法は、微小残存病変を標的とし、白血病モデルの再発を予防する Pluripotent stem cell-derived CAR-NK progenitor therapy targets minimal residual disease and prevents relapse in leukemia models

Zhiqian Wang∙ Leqiang Zhang ∙ Dehao Huang ∙ … ∙ Mengyun Zhang ∙ Fangxiao Hu ∙ Jinyong Wang
Cell Stem Cell  Published:February 24, 2026
DOI:https://doi.org/10.1016/j.stem.2026.01.013

Highlights

  • iNKP cells are abundantly generated from PSCs via an organoid culture system
  • CXCR4-expressing iNKP (R4-iNKP) cells produce iNK cells that persist over 80 days
  • CAR-R4iNKP cell infusion precisely protects animals from tumor challenges
  • Conventional chemotherapy combined with CAR-R4iNKP cell infusion eradicates MRD

Summary

Reducing relapse rates post-chemotherapy remains a major challenge for improving cancer therapy. Here, we developed a pluripotent stem cell-derived induced natural killer (NK) lineage-committed progenitor (iNKP) cell therapy in leukemia models. We generated abundant iNKP cells via an organoid culture system. The iNKP cells, engineered to express C-X-C motif chemokine receptor 4 (CXCR4) and chimeric antigen receptors (CARs), efficiently migrated to the bone marrow and generated CAR-iNK cells, which persisted in multiple organs and peripheral blood for over 80 days. Notably, CAR-iNKP cell infusion precisely protected animals from tumor challenges. Furthermore, a single low-dose infusion of CAR-iNKP cells following conventional chemotherapy reduced minimal residual disease and significantly prevented cancer relapse in human CD19+ B-ALL and CD7+ T-ALL tumor-bearing animals. CAR-iNKP cell treatment addresses the limitations of traditional CAR-NK cell infusion and offers a new strategy for future application in human cancer therapy.

細胞遺伝子工学
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