Journal Article

DKFZ-2025-01926

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Restoring NK Cell Cytotoxicity Post-Cryopreservation via Synthetic Cells.

Zhou, X. ; Zhang, S. ; Yang, W. ; Gonder, S. ; Sadjadi, Z. ; Piernitzki, N. ; Moter, A. ; Sharma, S. ; Largeot, A. ; Küchler, N. ; Kaschek, L. ; Schäfer, G. ; Schwarz, E. C. ; Eichler, H. ; Ullrich, E.DKFZ* ; Rieger, H. ; Staufer, O. ; Paggetti, J. ; Moussay, E. ; Hoth, M. ; Qu, B.

2025
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.1002/advs.202505731

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.

Keyword(s): 3D ; IL‐2 ; NK cells ; T cells ; cryopreservation ; cytotoxicity ; synthetic cells

Note: 2025 Nov;12(42):e05731

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Frankfurt (FM01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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