TY  - JOUR
AU  - Zhou, Xiangda
AU  - Zhang, Sijia
AU  - Yang, Wenjuan
AU  - Gonder, Susanne
AU  - Sadjadi, Zeinab
AU  - Piernitzki, Nils
AU  - Moter, Alina
AU  - Sharma, Shulagna
AU  - Largeot, Anne
AU  - Küchler, Nadja
AU  - Kaschek, Lea
AU  - Schäfer, Gertrud
AU  - Schwarz, Eva C
AU  - Eichler, Hermann
AU  - Ullrich, Evelyn
AU  - Rieger, Heiko
AU  - Staufer, Oskar
AU  - Paggetti, Jérôme
AU  - Moussay, Etienne
AU  - Hoth, Markus
AU  - Qu, Bin
TI  - Restoring NK Cell Cytotoxicity Post-Cryopreservation via Synthetic Cells.
JO  - Advanced science
VL  - nn
SN  - 2198-3844
CY  - Weinheim
PB  - Wiley-VCH
M1  - DKFZ-2025-01926
SP  - nn
PY  - 2025
N1  - epub
AB  - 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.
KW  - 3D (Other)
KW  - IL‐2 (Other)
KW  - NK cells (Other)
KW  - T cells (Other)
KW  - cryopreservation (Other)
KW  - cytotoxicity (Other)
KW  - synthetic cells (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40966444
DO  - DOI:10.1002/advs.202505731
UR  - https://inrepo02.dkfz.de/record/304817
ER  -