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Pretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation

Author

Listed:
  • Abdulla Berjis

    (University of Pennsylvania
    University of Pennsylvania)

  • Deeksha Muthumani

    (University of Pennsylvania
    University of Pennsylvania)

  • Oscar A. Aguilar

    (University of California; San Francisco)

  • Oz Pomp

    (University of Pennsylvania)

  • Omar Johnson

    (University of Pennsylvania)

  • Amanda V. Finck

    (University of Pennsylvania
    University of Pennsylvania)

  • Nils W. Engel

    (University of Pennsylvania)

  • Linhui Chen

    (University of Pennsylvania
    University of Pennsylvania)

  • Nicolas Plachta

    (University of Pennsylvania)

  • John Scholler

    (University of Pennsylvania)

  • Lewis L. Lanier

    (University of California; San Francisco)

  • Carl H. June

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Neil C. Sheppard

    (University of Pennsylvania
    University of Pennsylvania)

Abstract

Human natural killer (NK) cell-based therapies are under assessment for treating various cancers, but cryopreservation reduces both the recovery and function of NK cells, thereby limiting their therapeutic feasibility. Using cryopreservation protocols optimized for T cells, here we find that ~75% of NK cells die within 24 h post-thaw, with the remaining cells displaying reduced cytotoxicity. Using CRISPR-Cas9 gene editing and confocal microscopy, we find that cryopreserved NK cells largely die via apoptosis initiated by leakage of granzyme B from cytotoxic vesicles. Pretreatment of NK cells with a combination of Interleukins-15 (IL-15) and IL-18 prior to cryopreservation improves NK cell recovery to ~90-100% and enables equal tumour control in a xenograft model of disseminated Raji cell lymphoma compared to non-cryopreserved NK cells. The mechanism of IL-15 and IL-18-induced protection incorporates two mechanisms: a transient reduction in intracellular granzyme B levels via degranulation, and the induction of antiapoptotic genes.

Suggested Citation

  • Abdulla Berjis & Deeksha Muthumani & Oscar A. Aguilar & Oz Pomp & Omar Johnson & Amanda V. Finck & Nils W. Engel & Linhui Chen & Nicolas Plachta & John Scholler & Lewis L. Lanier & Carl H. June & Neil, 2024. "Pretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47574-0
    DOI: 10.1038/s41467-024-47574-0
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    References listed on IDEAS

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    1. Christoph Mark & Tina Czerwinski & Susanne Roessner & Astrid Mainka & Franziska Hörsch & Lucas Heublein & Alexander Winterl & Sebastian Sanokowski & Sebastian Richter & Nina Bauer & Thomas E. Angelini, 2020. "Cryopreservation impairs 3-D migration and cytotoxicity of natural killer cells," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
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