Restoring NK Cell Cytotoxicity Post‐Cryopreservation via Synthetic Cells

Natural killer (NK) cells are critical components of the first-line immune defense, responsible for eliminating tumorigenic cells. NK cell-based adoptive immunotherapy has gained increasing attention; however, cryopreservation, a standard technique for NK cell storage, significantly impairs NK cell cytotoxicity, particularly in physiological 3D environments. Here, we demonstrate that short-term co-culture with effector T cells markedly enhances NK cell motility and killing functionality. Notably, a brief 1-day co-culture is sufficient to restore cryopreservation-impaired NK cell functionality in 3D environments. This enhancement requires direct contact between T cells and NK cells, which facilitates localized high concentrations of IL-2 at the cell contact sites. To develop a controled, donor-independent solution, we demonstrate that synthetic T cells with surface-bound IL-2 exhibit superior efficiency in revitalizing cryopreserved NK cells. These findings uncover a previously unrecognized role for physical contact-mediated local IL-2 signaling and provide an efficient, cost-effective, and tunable strategy to rescue NK cell functionality post-cryopreservation, paving the way for more scalable, potent, and clinically viable NK cell-based immunotherapies.

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Publication Details

Journal
Advanced Science
Published
2025-09-18
DOI
https://doi.org/10.1002/advs.202505731
Primary Topic
Immune Cell Function and Interaction
Type
article
Field-Weighted Citation Impact
0.00

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article

Restoring NK Cell Cytotoxicity Post‐Cryopreservation via Synthetic Cells

Shulagna Sharma, Alina Moter, Nadja Küchler, Oskar Staufer et al.
Advanced Science
Immune Cell Function and Interaction
article

Restoring NK Cell Cytotoxicity Post‐Cryopreservation via Synthetic Cells

Shulagna Sharma, Alina Moter, Nadja Küchler, Oskar Staufer, Lea Kaschek, Jérôme Paggetti, Sijia Zhang, Hermann Eichler, Zeinab Sadjadi, Evelyn Ullrich, Heiko Rieger, Etienne Moussay, Markus Hoth, Gertrud Schäfer, Susanne Gonder, Anne Largeot, Wenjuan Yang, Xiangda Zhou, Eva C. Schwarz, Nils Piernitzki, Bin Qu
article en

Abstract

Natural killer (NK) cells are critical components of the first-line immune defense, responsible for eliminating tumorigenic cells. NK cell-based adoptive immunotherapy has gained increasing attention; however, cryopreservation, a standard technique for NK cell storage, significantly impairs NK cell cytotoxicity, particularly in physiological 3D environments. Here, we demonstrate that short-term co-culture with effector T cells markedly enhances NK cell motility and killing functionality. Notably, a brief 1-day co-culture is sufficient to restore cryopreservation-impaired NK cell functionality in 3D environments. This enhancement requires direct contact between T cells and NK cells, which facilitates localized high concentrations of IL-2 at the cell contact sites. To develop a controled, donor-independent solution, we demonstrate that synthetic T cells with surface-bound IL-2 exhibit superior efficiency in revitalizing cryopreserved NK cells. These findings uncover a previously unrecognized role for physical contact-mediated local IL-2 signaling and provide an efficient, cost-effective, and tunable strategy to rescue NK cell functionality post-cryopreservation, paving the way for more scalable, potent, and clinically viable NK cell-based immunotherapies.

Advanced ScienceVol. 12(42)
Goethe University Frankfurt (DE), Osnabrück University (DE), Second Military Medical University (CN), Institute for Transfusion Medicine (US), Leibniz-Institute for New Materials (DE), Luxembourg Institute of Health (LU), Helmholtz Institute for Pharmaceutical Research Saarland (DE), Max Planck-Bristol Centre for Minimal Biology (GB), Hochschule Osnabrück (DE), Frankfurt Cancer Institute (DE), Saarland University (DE)
Fondation Cancer, Deutsche Forschungsgemeinschaft, Fonds National de la Recherche Luxembourg, Fonds De La Recherche Scientifique - FNRS, Universität des Saarlandes, Deutsche Krebshilfe, Dr. Rolf M. Schwiete Stiftung, Leibniz-Gemeinschaft
Openalex Percentile: Top 73%
Immune Cell Function and Interaction
DOIOpen Access PDFOpenAlex
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