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
CD133 靶向 CAR-NK92MI 细胞在结直肠癌中的抗肿瘤作用
英文原题：Anti-tumor effects of CD133-targeted CAR-NK92MI cells in colorectal cancer.
查看英文原题
Anti-tumor effects of CD133-targeted CAR-NK92MI cells in colorectal cancer.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
靶向 CD133 的 CAR-NK92MI 细胞对结直肠癌显示出有前景的抗肿瘤活性，并可能为开发针对 CRC 的现货型细胞治疗产品提供潜在策略。
研究思路结论见上方概要
背景
结直肠癌（CRC）是一种高度侵袭性的恶性肿瘤，持续威胁着许多人的生命。嵌合抗原受体NK 细胞（CAR-NK）疗法已成为CRC一种有前景的治疗方法。CD133是许多实体瘤尤其是CRC的重要标志物。
方法
在本研究中，我们利用慢病毒系统构建了靶向CD133的CAR-NK92MI细胞，并通过流式细胞术分析CAR表达。通过CCK-8实验评估导入CAR后NK92MI细胞的增殖情况。通过LDH释放、Calcein-AM/PI染色和TUNEL染色评估对靶细胞的体外细胞毒性，并通过检测IFN-分泌评估效应细胞活化。进一步通过Transwell侵袭实验、划痕愈合实验和3D肿瘤球体系评估CAR-NK92MI细胞对靶细胞侵袭和迁移的影响。同时还评估了体内抗肿瘤活性。
结果
CAR在NK92MI细胞中成功表达，且未显著影响细胞增殖。体外实验中，CAR-NK92MI细胞对靶细胞表现出增强的杀伤活性，并增加了IFN-分泌。CAR-NK92MI细胞还抑制了靶细胞侵袭和球体生长。体内实验结果与体外结果一致。
展开英文摘要原文
METHODS
In this study, we generated CD133-targeted CAR-NK92MI cells using a lentiviral system and analyzed CAR expression by flow cytometry. The proliferation of NK92MI cells after CAR introduction was evaluated by CCK-8 assay. In vitro cytotoxicity against target cells was assessed by LDH release, Calcein-AM/PI staining, and TUNEL staining, and effector cell activation was evaluated by measuring IFN- secretion. The effects of CAR-NK92MI cells on target-cell invasion and migration were further assessed by Transwell invasion assays, wound-healing assays, and a 3D tumor-spheroid system. In vivo antitumor activity was also evaluated.
RESULTS
CAR was successfully expressed in NK92MI cells without significantly affecting cell proliferation. In vitro, CAR-NK92MI cells showed enhanced killing activity against target cells and increased IFN- secretion. CAR-NK92MI cells also suppressed target-cell invasion and spheroid growth. The in vivo findings were consistent with the in vitro results.
CONCLUSION
CD133-targeted CAR-NK92MI cells showed promising antitumor activity against colorectal cancer and may provide a potential strategy for developing an off-the-shelf cell therapy product for CRC.
论文信息
- 作者
- Zhang Y、Huang Z、Tong C、Qi Z、Zhang S
- 第一作者单位
- Medical College, Guangxi University, Nanning, People's Republic of China.China
- 通讯作者单位
- Medical College, Guangxi University, Nanning, People's Republic of China; Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People's Republic of China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, People's Republic of China. Electronic address: cnfj@xmu.edu.cn.China
- 期刊
- Cytotherapy2026 Sep
- 原文标识
- PubMed 42462589 · DOI 10.1016/j.jcyt.2026.102123