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

Autor: Berjis A; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Abdulla.Berjis@Pennmedicine.upenn.edu.; School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA. Abdulla.Berjis@Pennmedicine.upenn.edu., Muthumani D; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA., Aguilar OA; Department of Microbiology and Immunology and Parker Institute of Cancer Immunotherapy, University of California; San Francisco, San Francisco, CA, USA., Pomp O; Department of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Johnson O; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA., Finck AV; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Engel NW; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA., Chen L; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Biomedical Informatics, the Bioinformatic Core, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Plachta N; Department of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Scholler J; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA., Lanier LL; Department of Microbiology and Immunology and Parker Institute of Cancer Immunotherapy, University of California; San Francisco, San Francisco, CA, USA., June CH; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA, USA.; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA., Sheppard NC; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. neil.sheppard@pennmedicine.upenn.edu.; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. neil.sheppard@pennmedicine.upenn.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 10; Vol. 15 (1), pp. 3937. Date of Electronic Publication: 2024 May 10.
DOI: 10.1038/s41467-024-47574-0
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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