2. Academic Validation
  3. Pluripotent stem cell-derived CAR-NK progenitor therapy targets minimal residual disease and prevents relapse in leukemia models

Pluripotent stem cell-derived CAR-NK progenitor therapy targets minimal residual disease and prevents relapse in leukemia models

  • Cell Stem Cell. 2026 Mar 5;33(3):405-420.e6. doi: 10.1016/j.stem.2026.01.013.
Zhiqian Wang 1,  Leqiang Zhang 1,  Dehao Huang 2,  Chengxiang Xia 2,  Qitong Weng 3,  Yunqing Lin 1,  Yanhong Liu 3,  Zhenghan Liu 4,  Ruowen Yi 1,  Fan Zhang 1,  Yaoqin Zhao 1,  Jiaxin Wu 1,  Hanmeng Qi 2,  Lijuan Liu 5,  Yiyuan Shen 2,  Yi Chen 2,  Yanping Zhu 5,  Tongjie Wang 6,  Mengyun Zhang 7,  Fangxiao Hu 8,  Jinyong Wang 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 101408, China.
  • 2 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • 3 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  • 4 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Science, Northeast Agricultural University, Harbin 150030, China.
  • 5 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • 6 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China. Electronic address: [email protected].
  • 7 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China. Electronic address: [email protected].
  • 8 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China. Electronic address: [email protected].
  • 9 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 101408, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China. Electronic address: [email protected].
PMID: 41742420 DOI: 10.1016/j.stem.2026.01.013
Abstract

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.

Keywords

CAR-NK progenitor therapy; CXCR4; cancer minimal residual disease; chemotherapy; persistence; pluripotent stem cell.

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