RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
脐带血来源的 NK 细胞作为过继性细胞治疗可行且有效的来源
英文原题：Umbilical cord blood-derived natural killer cells as a viable and potent source for adoptive cell therapy.
查看英文原题
Umbilical cord blood-derived natural killer cells as a viable and potent source for adoptive cell therapy.
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研究思路按摘要原文分段
背景
自然杀伤（NK）细胞是固有免疫应答的关键组成部分，能够不依赖主要组织相容性复合体限制性杀伤多种肿瘤细胞和病毒感染细胞。脐带血（UCB）是NK细胞的一个有前景的来源，因其可获得性、较低的人类白细胞抗原要求以及较低的移植物抗宿主病风险。
方法
在本研究中，UCB来源的NK细胞在良好生产规范条件下使用CSTX002进行体外扩增14天。
结果
扩增的NK细胞在冷冻保存后表现出高活力（94.8 ± 1.3%），并在180天后（87.7 ± 1.1%）和365天后（91 ± 8.1%；n = 4）保持稳定。免疫表型（CD56⁺CD3⁻）得以保留，长期冷冻保存后超过90%的细胞维持该表型。使用calcein-AM法针对K562和HL-60白血病细胞系评估的细胞毒活性在冷冻保存后仍保持强效。在第14天，NK细胞在0.5:1效靶比下杀伤54.55 ± 10.92%的K562细胞，在40:1效靶比下杀伤98.60 ± 0.66%。冷冻保存的NK细胞表现出相当的活性，在相同效靶比下分别杀伤44.56 ± 11.98%和97.64 ± 2.36%的靶细胞。
结论
这些发现支持生产冷冻保存的UCB来源NK细胞作为稳定有效的“现货型”产品用于过继性免疫治疗的可行性，尤其是在急性髓系白血病的治疗中，具有可扩展性、标准化和快速临床部署的优势。
展开英文摘要原文
METHODS
In this study, UCB-derived NK cells were expanded ex vivo for 14 days using CSTX002 under Good Manufacturing Practice conditions.
RESULTS
The expanded NK cells exhibited high viability (94.8 ± 1.3%) cryopreservation, which remained stable after 180 days (87.7 ± 1.1%) and after 365 days (91 ± 8.1%; n = 4). The immunophenotype (CD56⁺CD3⁻) was preserved, with more than 90% of cells maintaining this profile after long-term cryopreservation. Cytotoxic activity, assessed using a calcein-AM assay against K562 and HL-60 leukemia cell lines, remained robust after cryopreservation. At day 14, NK cells killed 54.55 ± 10.92% of K562 cells at a 0.5:1 effector-to-target ratio and 98.60 ± 0.66% at a 40:1 ratio. Cryopreserved NK cells demonstrated comparable activity, killing 44.56 ± 11.98% and 97.64 ± 2.36% of target cells at the same respective ratios.
CONCLUSIONS
These findings support the feasibility of producing cryopreserved, UCB-derived NK cells as a stable and effective "off-the-shelf" product for adoptive immunotherapy, particularly in the treatment of acute myeloid leukemia, with advantages in scalability, standardization, and rapid clinical deployment.
论文信息
- 作者
- Alves-Paiva RM、Coa LL、Azevedo JT、da Silva JR、de Godoy JAP、Sielski MS、Zanetti LC、Oliveira DC
- 单位
- Department of Hemotherapy and Cell Therapy, Einstein Hospital Israelita, São Paulo, Brazil. Electronic address: raquel.paiva@einstein.br.Israel
- 期刊
- Cytotherapy2026 May
- 原文标识
- PubMed 41762953 · DOI 10.1016/j.jcyt.2026.102079