RT Journal Article
SR Electronic
T1 Cryopreservation impairs cytotoxicity and migration of NK cells in 3-D tissue: Implications for cancer immunotherapy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 812172
DO 10.1101/812172
A1 Christoph Mark
A1 Tina Czerwinski
A1 Susanne Roessner
A1 Astrid Mainka
A1 Franziska Hörsch
A1 Lucas Heublein
A1 Alexander Winterl
A1 Sebastian Sanokowski
A1 Sebastian Richter
A1 Nina Bauer
A1 Gerold Schuler
A1 Ben Fabry
A1 Caroline J. Voskens
YR 2019
UL http://biorxiv.org/content/early/2019/10/21/812172.abstract
AB Natural killer (NK) cells are important effector cells in the immune response to cancer. Clinical trials on adoptively transferred NK cells in patients with solid tumors, however, have thus far been unsuccessful. As NK cells need to pass stringent safety evaluation for clinical use, the cells are cryopreserved to bridge the necessary evaluation time. While a degranulation assay confirms the ability of cryopreserved NK cells to kill target cells, we find a significant decrease of cytotoxicity after cryopreservation in a chromium release assay. We complement these standard assays with measurements of NK cell motility and cytotoxicity in 3-dimensional (3-D) collagen gels that serve as a substitute for connective tissue. We find a 5.6 fold decrease of cytotoxicity after cryopreservation and establish that this is mainly caused by a 6-fold decrease in the fraction of motile NK cells. These findings may explain the persistent failure of NK cell therapy in patients with solid tumors and highlight the crucial role of a 3-D environment for testing NK cell function.Synopsis Cryopreservation of natural killer (NK) cells dramatically impairs their motility and cytotoxicity in tissue. This finding may explain the persistent failure of clinical trials in which NK cell therapy is used for treating solid tumors.