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Updated: Jan 26, 2026

Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Induction of human pluripotent stem cell-derived natural killer cells for immunotherapy under chemically defined
Hiroyuki Matsubara1, Akira Niwa2, Tatsutoshi Nakahata2
1Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan; Training Program of Leaders for Integrated Medical System, Kyoto University, Kyoto, Japan.
Abstract:
Natural killer (NK) cells are innate lymphocytes and show cytotoxicity against tumor cells without prior antigen specific stimulation. Because of their innate properties, NK cells are being considered for immunotherapies against various malignancies or leukemia. Human pluripotent stem cells (hPSCs) are capable of inducing enough NK cells for allogeneic transplantation. However, current induction protocols require feeder cells or human or bovine serum for the differentiation and expansion of NK cells, which incurs potential risk for contamination and may cause lot dependency in the cells. To address these issues, here we established a differentiation protocol for developing functional NK cells from hPSCs under a completely chemically-defined condition. The resultant PSC-derived NK cells show comparable phenotypes to those produced under serum-containing condition, exerting strong killing potential against a leukemia cell line in vitro and resistance to tumor growth in vivo. Our protocol can be a useful tool for applying PSC-derived NK cells to future cellular cancer immunotherapies.
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