Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells

Abstract

Cell therapy is emerging as a very promising therapeutic modality against cancer, spearheaded by the clinical success of chimeric antigen receptor (CAR) modified T cells for B cell malignancies. Currently, FDA-approved CAR-T cell products are based on engineering of autologous T cells harvested from the patient, typically using a central manufacturing facility for gene editing before the product can be delivered to the clinic and infused to the patients. For a broader implementation of advanced cell therapy and to reduce costs, it would be advantageous to use allogeneic “universal” cell therapy products that can be stored in cell banks and provided upon request, in a manner analogous to biopharmaceutical drug products. In this review, we outline a roadmap for development of off-the-shelf cell therapy based on natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs). We discuss strategies to engineer iPSC-derived NK (iPSC-NK) cells for enhanced functional potential, persistence, and homing.

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Acknowledgements

This work was supported by grants from the Swedish Research Council, the Swedish Children’s Cancer Society, the Swedish Cancer Society, the Karolinska Institutet, the Norwegian Cancer Society, the Norwegian Research Council, the South-Eastern Norway Regional Health Authority, and the KG Jebsen Center for Cancer Immunotherapy.

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Correspondence to Karl-Johan Malmberg.

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K.J. Malmberg and D.S. Kaufman serve on the Scientific Advisory Board of Fate Therapeutics and obtain research support. Bahram Valamehr is employed by Fate Therapeutics. The respective relationships have been reviewed and managed by University of San Diego California, Oslo University Hospital, and Karolinska Institutet in accordance with the institutions’ conflict of interest policies.

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This article is a contribution to the special issue on Anti-cancer Immunotherapy: Breakthroughs and Future Strategies -- Guest Editor: Mads Hald Andersen

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Saetersmoen, M.L., Hammer, Q., Valamehr, B. et al. Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells. Semin Immunopathol 41, 59–68 (2019). https://doi.org/10.1007/s00281-018-0721-x

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Keywords

  • Induced pluripotent stem cells
  • Natural killer cells
  • Off-the-shelf
  • Cell therapy
  • Chimeric antigen receptor
  • Cancer immunotherapy