Directed Differentiation of Natural Killer Cells from Human Induced Pluripotent Stem Cells: From Developmental Cues to In vitro Production
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Abstract
Natural killer (NK) cells are currently explored for cell therapy due to their innate tumour-killing properties. Their potential for adoptive immunotherapy has garnered significant attention, especially as an allogeneic cell source for cancer treatment due to their graft-versus-leukaemia effect and the safety profile. However, challenges involving ex vivo expansion of primary NK cells have hindered, to a certain extent, their clinical application. Hence, alternative cell source which can preferably be provided off-the-shelf are needed. Human-induced pluripotent stem cells have emerged as the promising cell source for producing homogenous NK cells under highly defined conditions for clinical treatment. In view of this, the understanding of the differentiation signalling cues underlying the development of NK cells is important to ensure highly efficient production of NK cells can be achieved in vitro. In this review, we briefly describe the recent chimeric-antigen receptor (CAR) technology used in engineering tumour-specific T cells and their current limitations, as well as summarizing the role of NK cells as an alternative cell source in adoptive immune cell therapy, the differentiation signalling from the view of NK cell development in human, comparing the current differentiation protocols using human induced pluripotent stem cells.
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