The ability of natural killer (NK) cells to mediate potent antitumor immunity in clinical adoptive transfer settings relies, in large part, on their ability to retain cytotoxic function following cryopreservation. To avoid potential systemic toxicities associated with infusions of NK cells into patients in the presence of dimethylsulfoxide (DMSO), interest in alternative cryoprotective agents (CPAs) with improved safety profiles has grown. Despite the development of various sugars, amino acids, polyols, and polyampholytes as cryoprotectants, their ability to promote protection from intracellular cryodamage is limited because they mostly act outside of the cell. Though ways to shuttle cryoprotectants intracellularly exist, NK cells' high aversity to manipulation and freezing has meant they are highly understudied as targets for the development of new cryopreservation approaches. Here, the first example of a safe and efficient platform for the intracellular delivery of non-DMSO CPAs to NK cells is presented. Biocompatible chitosan-based nanoparticles are engineered to mediate the efficient DMSO-free cryopreservation of NK cells. NK cells cryopreserved in this way retain potent cytotoxic, degranulation, and cytokine production functions against tumor targets. This not only represents the first example of delivering nanoparticles to NK cells, but illustrates the clinical potential in manufacturing safer allogeneic adoptive immunotherapies "off the shelf."

中文翻译：

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纳米颗粒介导的自然杀伤细胞的细胞内保护可避免冷冻损伤并保留有效的抗肿瘤功能。

自然杀伤 (NK) 细胞在临床过继转移环境中介导有效抗肿瘤免疫的能力在很大程度上依赖于它们在冷冻保存后保留细胞毒功能的能力。为了避免在二甲基亚砜 (DMSO) 存在的情况下将 NK 细胞输注到患者体内时可能产生的潜在全身毒性，人们对安全性更高的替代冷冻保护剂 (CPA) 的兴趣日益浓厚。尽管开发了各种糖、氨基酸、多元醇和聚两性电解质作为冷冻保护剂，但它们促进细胞内冷冻损伤保护的能力有限，因为它们主要在细胞外起作用。尽管存在在细胞内运送冷冻保护剂的方法，但 NK 细胞对操作和冷冻的高度厌恶意味着它们作为开发新冷冻保存方法的目标而受到高度重视。在此，提出了用于将非 DMSO CPA 细胞内递送至 NK 细胞的安全高效平台的第一个示例。生物相容性基于壳聚糖的纳米粒子经过精心设计，可介导 NK 细胞的高效无 DMSO 冷冻保存。以这种方式冷冻保存的 NK 细胞保留了针对肿瘤靶标的有效细胞毒性、脱颗粒和细胞因子产生功能。这不仅代表了将纳米粒子递送至 NK 细胞的第一个例子，而且说明了制造“现成的”更安全的同种异体过继免疫疗法的临床潜力。