Armored IL15 or IL15 receptor adaptors enhance proliferation and anti-tumor activity of CD19-targeted CAR-NK cells
10.16016/j.2097-0927.202507093
- VernacularTitle:装甲IL15或IL15受体连接体增强靶向CD19的CAR-NK细胞增殖与抗肿瘤活性
- Author:
Mengyuan YU
1
;
Xiuying LIU
;
Xiaotian ZHANG
;
Jiaying WANG
;
Zhiming LING
;
Jianxun WANG
Author Information
1. 北京中医药大学生命科学学院
- Keywords:
chimeric antigen receptor NK cells;
interleukin 15;
anti-tumor activity;
proliferation
- From:
Journal of Army Medical University
2025;47(23):2903-2912
- CountryChina
- Language:Chinese
-
Abstract:
Objective To construct CD19-targeted chimeric antigen receptor natural killer(CAR-NK)cells armored with interleukin15(IL15)or IL15 receptor-linker(RLI)and preliminarily validate their proliferative capacity and anti-tumor activity in vitro.Methods Natural killer cells(NK92 and NK92MI)from patients with human malignant non-Hodgkin lymphoma were cultured,and CD19-targeted CAR-NK cells armored with IL15 or RLI were prepared using retroviral vector particles.IL15 secretion was measured by ELISA,and proliferative capacity was assessed via CFSE dilution assays.Human B-lymphocytic leukemia cells(Nalm6-GFP-Luc)and human colon cancer cells overexpressing CD19(hCD19-SW620-GFP-Luc)were cultured,with surface CD19 expression confirmed(>99%positivity for both).Anti-tumor activity was evaluated by measuring cytotoxicity at effector-to-target(E:T)ratios using luciferase-based assays(4/12 h),detecting surface CD107a expression via flow cytometry,and quantifying cytokine release using CBA assays.Results NK92/NK92MI-CD19 CAR cells armored with IL15 or RLI were successfully generated.IL15 secretion was significantly higher in armored groups versus non-armored controls(P<0.01).Without IL-2 stimulation,IL15/RLI enhanced CAR-NK proliferation(P<0.05).Both armored designs significantly increased tumor-killing efficiency(P<0.05)and CD107a degranulation.IL15/RLI-armored NK92-CD19 CAR cells exhibited elevated release of IL2,IL10,IL6,TNF-α,sFas,IFN-γ,and Granulysin(P<0.05),while armored NK92MI-CD19 CAR cells showed additional increases in Granzyme A,Granzyme B,and Perforin(P<0.05).Conclusion IL15/RLI-armored NK92/NK92MI-CD19 CAR cells demonstrate potent anti-tumor activity,supporting their combined clinical therapeutic potential for tumors.
