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ORIGINAL RESEARCH article

Front. Immunol.
Sec. NK and Innate Lymphoid Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1463736
This article is part of the Research Topic Killer Re-Design: Synthetic Biology Approaches for Natural Killer-Cell Therapy View all 7 articles

Comparative analysis of iPSC-derived NK cells from two differentiation strategies reveals distinct signatures and cytotoxic activities

Provisionally accepted
Matthias HUYGHE Matthias HUYGHE 1Christophe Desterke Christophe Desterke 1Jusuf IMERI Jusuf IMERI 1Nathan Belliard Nathan Belliard 1Diana Chaker Diana Chaker 1,2Noufissa Oudrirhi Noufissa Oudrirhi 1,3Hudson Bezerra Hudson Bezerra 1Ali G. Turhan Ali G. Turhan 1,2,4Annelise Bennaceur Griscelli Annelise Bennaceur Griscelli 1,2,3,4Frank Griscelli Frank Griscelli 1,2,5,6*
  • 1 Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-S-1310, Villejuif, France
  • 2 UMS 045- CITHERA « Center for iPSC Cell Therapy », National Infrastructure INGESTEM, Evry, France
  • 3 Service d’Hématologie Biologique Unité d’Onco-Hématologie moléculaire et Cytogénétique APHP, Hôpital Universitaire Paris Sud, Paul Brousse, Villejuif, France
  • 4 Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, Île-de-France, France
  • 5 Université Paris Descartes, Faculté Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France
  • 6 Institut Gustave-Roussy, Département de Biologie et Pathologie Médicale, service de pathologie morphologique, Villejuif, France

The final, formatted version of the article will be published soon.

    The ability to generate natural killer (NK) cells from induced pluripotent stem cells (iPSCs) has given rise to new possibilities for the large-scale production of homogeneous immunotherapeutic cellular products and opened new avenues towards the creation of "off-the-shelf" cancer immunotherapies.However, the differentiation of NK cells from iPSCs remains poorly understood, particularly regarding the ontogenic landscape of iPSC-derived NK (iNK) cells produced in vitro and the influence that the differentiation strategy employed may have on the iNK profile. To investigate this question, we conducted a comparative analysis of two sets of iNK cells generated from the same iPSC line using two different protocols: (i) a short-term, clinically compatible feeder-free protocol corresponding to primitive hematopoiesis, and (ii) a lymphoid-based protocol representing the definitive hematopoietic step. Our work demonstrated that both protocols are capable of producing functional iNK cells.However, the two sets of resulting iNKs exhibited distinct phenotypes and transcriptomic profiles. The lymphoid-based differentiation approach generated iNKs with a more mature and activated profile, which demonstrated higher cytotoxicity against cancer cell lines compared to iNK cells produced under short-term feeder-free conditions suggesting that the differentiation strategy must be considered when designing iNK cell-based adoptive immunotherapies.

    Keywords: induced pluripotent stem cells (IPSC), natural killer (NK) cells, Feeder-free differentiation, Immunotherapy, Lymphoid based differentiation

    Received: 12 Jul 2024; Accepted: 10 Sep 2024.

    Copyright: © 2024 HUYGHE, Desterke, IMERI, Belliard, Chaker, Oudrirhi, Bezerra, Turhan, Bennaceur Griscelli and Griscelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Frank Griscelli, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-S-1310, Villejuif, France

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