A scalable, spin-free approach to generate enhanced induced pluripotent stem cell-derived natural killer cells for cancer immunotherapy.

Autor: Rossi GR; Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia., Sun J; Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia., Lin CY; Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia., Wong JK; Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia., Alim L; Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia., Lam PY; Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia., Khosrotehrani K; Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia., Wolvetang E; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, QLD, Australia., Cheetham SW; Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, QLD, Australia.; BASE Facility, University of Queensland, St Lucia, QLD, Australia., Derrick EB; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia., Amoako A; The Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia., Lehner C; The Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia., Brooks AJ; Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia., Beavis PA; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia., Souza-Fonseca-Guimaraes F; Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia.
Jazyk: angličtina
Zdroj: Immunology and cell biology [Immunol Cell Biol] 2024 Nov; Vol. 102 (10), pp. 924-934. Date of Electronic Publication: 2024 Sep 13.
DOI: 10.1111/imcb.12820
Abstrakt: Natural killer (NK) cells play a vital role in innate immunity and show great promise in cancer immunotherapy. Traditional sources of NK cells, such as the peripheral blood, are limited by availability and donor variability. In addition, in vitro expansion can lead to functional exhaustion and gene editing challenges. This study aimed to harness induced pluripotent stem cell (iPSC) technology to provide a consistent and scalable source of NK cells, overcoming the limitations of traditional sources and enhancing the potential for cancer immunotherapy applications. We developed human placental-derived iPSC lines using reprogramming techniques. Subsequently, an optimized two-step differentiation protocol was introduced to generate high-purity NK cells. Initially, iPSCs were differentiated into hematopoietic-like stem cells using spin-free embryoid bodies (EBs). Subsequently, the EBs were transferred to ultra-low attachment plates to induce NK cell differentiation. iPSC-derived NK (iNK) cells expressed common NK cell markers (NKp46, NKp30, NKp44, CD16 and eomesodermin) at both RNA and protein levels. iNK cells demonstrated significant resilience to cryopreservation and exhibited enhanced cytotoxicity. The incorporation of a chimeric antigen receptor (CAR) construct further augmented their cytotoxic potential. This study exemplifies the feasibility of generating iNK cells with high purity and enhanced functional capabilities, their improved resilience to cryopreservation and the potential to have augmented cytotoxicity through CAR expression. Our findings offer a promising pathway for the development of potential cellular immunotherapies, highlighting the critical role of iPSC technology in overcoming challenges associated with traditional NK cell sources.
(© 2024 The Author(s). Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)
Databáze: MEDLINE
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