CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
共表达 IL-21 增强型 NKG2D CAR-NK 细胞疗法治疗肺癌
英文原题：Co-expression of IL-21-Enhanced NKG2D CAR-NK cell therapy for lung cancer.
查看英文原题
Co-expression of IL-21-Enhanced NKG2D CAR-NK cell therapy for lung cancer.
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研究概要
我们的研究结果为使用 NKG2D-IL-21 CAR-NK 细胞疗法治疗肺癌提供了一种新的选择。
研究思路结论见上方概要
背景
过继性细胞疗法在治疗血液系统恶性肿瘤方面取得了巨大成功。然而，CAR-T（CAR-T）细胞疗法的生产仍面临各种困难。自然杀伤（NK）-92是一种可连续扩增的细胞系，为患者自身免疫细胞提供了一种有前景的替代选择。
方法
我们通过共表达NK 细胞2族成员D（NKG2D）和IL-21建立了CAR-NK细胞，并在体外和体内评估了NKG2D-IL-21 CAR-NK细胞治疗肺癌的疗效。
结果
我们的数据表明，IL-21的表达以剂量依赖的方式有效增强了NKG2D CAR-NK细胞对肺癌细胞的细胞毒性，并在体外和体内抑制了肿瘤生长。此外，NKG2D-IL-21 CAR-NK细胞的增殖得到增强，而这些细胞的凋亡和耗竭受到抑制。在机制上，IL-21介导的NKG2D CAR-NK细胞功能是通过激活AKT信号通路实现的。
展开英文摘要原文
BACKGROUND
Adoptive cell therapy has achieved great success in treating hematological malignancies. However, the production of chimeric antigen receptor T (CAR-T) cell therapy still faces various difficulties. Natural killer (NK)-92 is a continuously expandable cell line and provides a promising alternative for patient's own immune cells.
METHODS
We established CAR-NK cells by co-expressing natural killer group 2 member D (NKG2D) and IL-21, and evaluated the efficacy of NKG2D-IL-21 CAR-NK cells in treating lung cancer in vitro and in vivo.
RESULTS
Our data suggested that the expression of IL-21 effectively increased the cytotoxicity of NKG2D CAR-NK cells against lung cancer cells in a dose-dependent manner and suppressed tumor growth in vitro and in vivo. In addition, the proliferation of NKG2D-IL-21 CAR-NK cells were enhanced while the apoptosis and exhaustion of these cells were suppressed. Mechanistically, IL-21-mediated NKG2D CAR-NK cells function by activating AKT signaling pathway.
CONCLUSION
Our findings provide a novel option for treating lung cancer using NKG2D-IL-21 CAR-NK cell therapy.
论文信息
- 作者
- Zhang Y、Zhang C、He M、Xing W、Hou R、Zhang H
- 第一作者单位
- Department of Oncology, Shenyang 242 Hospital, 110034, Shenyang, China.China
- 通讯作者单位
- Department of Respiratory and Critical Care Medicine, Yidu Central Hospital of Weifang, 262500, Weifang, China. miniwolf1993@163.com.China
- 期刊
- BMC cancer2024 Jan 23
- 原文标识
- PubMed 38263004 · DOI 10.1186/s12885-023-11806-1
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