IL-21 增强的 NKG2D CAR-NK 细胞疗法治疗肺癌。

Co-expression of IL-21-Enhanced NKG2D CAR-NK cell therapy for lung cancer.

机构信息

Department of Oncology, Shenyang 242 Hospital, 110034, Shenyang, China.

Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, 610072, Chengdu, China.

出版信息

BMC Cancer. 2024 Jan 23;24(1):119. doi: 10.1186/s12885-023-11806-1.

DOI:10.1186/s12885-023-11806-1

PMID:38263004

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10807083/

Abstract

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.

摘要

背景

过继细胞疗法在治疗血液恶性肿瘤方面取得了巨大成功。然而，嵌合抗原受体 T（CAR-T）细胞疗法的生产仍然面临各种困难。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有前途的替代方案。

方法

我们通过共表达自然杀伤组 2 成员 D（NKG2D）和白细胞介素 21（IL-21）来构建 CAR-NK 细胞，并评估 NKG2D-IL-21 CAR-NK 细胞在体外和体内治疗肺癌的疗效。

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，并抑制了体外和体内的肿瘤生长。此外，NKG2D-IL-21 CAR-NK 细胞的增殖增强，而这些细胞的凋亡和耗竭受到抑制。机制上，IL-21 通过激活 AKT 信号通路介导 NKG2D CAR-NK 细胞的功能。