A research team led by Jinyong Wang at the Chinese Academy of Sciences says it has developed a three-step laboratory process that can generate large numbers of induced natural killer (iNK) cells — including CD19 CAR-engineered versions — starting from CD34+ stem and progenitor cells from umbilical cord blood. In a Nature Biomedical Engineering study published in October 2025, the researchers reported output on the order of tens of millions of NK cells from a single starting CD34+ cell in their system and showed anti-tumour activity in mouse models of blood cancers, while also reporting sharply reduced viral-vector use for CAR delivery compared with approaches that modify mature NK cells.
Researchers led by Prof. Jinyong Wang at the Institute of Zoology, Chinese Academy of Sciences, reported a method designed to streamline production of induced natural killer (iNK) cells and CD19 chimeric antigen receptor-engineered iNK (CAR-iNK) cells from umbilical cord blood-derived CD34+ haematopoietic stem and progenitor cells (HSPCs).
The approach aims to avoid some of the difficulties the team associates with engineering mature NK cells — including variability between donor-derived cells and lower gene-transfer efficiency — by introducing genetic modification earlier, at the CD34+ HSPC stage.
According to a research summary from the Chinese Academy of Sciences and the journal paper, the method uses a three-stage system. First, CD34+ HSPCs (or CD19 CAR-transduced HSPCs) are expanded with irradiated AFT024 feeder cells, with the team reporting roughly 800- to 1,000-fold expansion over about 14 days. In the second stage, the expanded cells are cultured with OP9 feeder cells to form artificial haematopoietic organoid aggregates that support commitment toward the NK lineage. In the final stage, the committed cells are matured and expanded further to produce iNK or CAR-iNK cell products; the journal article reports high CD16 expression and no detectable T-cell contamination in the resulting products.
In terms of scale, the Nature Biomedical Engineering article reports that starting from a single cord-blood CD34+ cell, the system produced 14–83 million mature iNK cells and 7–32 million CAR-iNK cells under the study’s conditions. A Chinese Academy of Sciences/ScienceDaily write-up highlighted examples of 14 million iNK cells and 7.6 million CAR-iNK cells from a single CD34+ cell, and said the team estimated that one-fifth of a typical cord-blood unit could theoretically yield enough cells for thousands to tens of thousands of treatment doses.
The researchers also reported reduced viral-vector requirements for CAR engineering compared with approaches that transduce mature NK cells, describing vector use on the order of about 1/140,000 by day 42 and 1/600,000 by day 49 in their culture timeline.
In preclinical experiments described in the paper and accompanying research summary, CD19 CAR-iNK cells showed anti-tumour activity in xenograft mouse models, including cell line-derived xenografts (CDX) and patient-derived xenografts (PDX) involving human B-cell acute lymphoblastic leukaemia (B-ALL), where the CAR-iNK treatment reduced tumour growth and extended survival.
The study, authored by Fangxiao Hu and colleagues, was published by Nature Biomedical Engineering on 7 October 2025 (DOI: 10.1038/s41551-025-01522-5). The ScienceDaily release states the work was supported by the Ministry of Science and Technology of the People’s Republic of China and the National Natural Science Foundation of China, among other funding sources.
