El Assal Rami, Abou-Elkacem Lotfi, Tocchio Alessandro, Pasley Shannon, Matosevic Sandro, Kaplan David L, Zylberberg Claudia, Demirci Utkan
Bio-Acoustic-MEMS in Medicine (BAMM) Laboratories Canary Center at Stanford for Cancer Early Detection Department of Radiology Stanford University School of Medicine Palo Alto CA 94304 USA.
Molecular Imaging Program at Stanford (MIPS) Department of Radiology Stanford University School of Medicine Palo Alto CA 94304 USA.
Adv Sci (Weinh). 2019 Jan 27;6(6):1802045. doi: 10.1002/advs.201802045. eCollection 2019 Mar 20.
The ability to cryopreserve natural killer (NK) cells has a significant potential in modern cancer immunotherapy. Current cryopreservation protocols cause deterioration in NK cell viability and functionality. This work reports the preservation of human cytokine-activated NK cell viability and function following cryopreservation using a cocktail of biocompatible bioinspired cryoprotectants (i.e., dextran and carboxylated ε-poly-L-lysine). Results demonstrate that the recovered NK cells after cryopreservation and rewarming maintain their viability immediately after thawing at a comparable level to control (dimethyl sulfoxide-based cryopreservation). Although, their viability drops in the first day in culture compared to controls, the cells grow back to a comparable level to controls after 1 week in culture. In addition, the anti-tumor functional activity of recovered NK cells demonstrates higher cytotoxic potency against leukemia cells compared to control. This approach presents a new direction for NK cell preservation, focusing on function and potentially enabling storage and distribution for cancer immunotherapy.
在现代癌症免疫疗法中,冷冻保存自然杀伤(NK)细胞的能力具有巨大潜力。当前的冷冻保存方案会导致NK细胞活力和功能下降。这项工作报道了使用生物相容性仿生冷冻保护剂(即右旋糖酐和羧化ε-聚-L-赖氨酸)混合物冷冻保存后人细胞因子激活的NK细胞活力和功能得以保留。结果表明,冷冻保存和复温后回收的NK细胞在解冻后立即保持其活力,与对照(基于二甲基亚砜的冷冻保存)相当。尽管与对照相比,它们在培养的第一天活力下降,但在培养1周后细胞生长恢复到与对照相当的水平。此外,回收的NK细胞的抗肿瘤功能活性显示出比对照更高的对白血病细胞的细胞毒性效力。这种方法为NK细胞保存提供了一个新方向,专注于功能,并有可能实现癌症免疫疗法的储存和分配。