1. Therapeutic effect of small extracellular vesicles from cytokine-induced memory-like natural killer cells on solid tumors.
- Author
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Shi, Yinghong, Chen, Yanxia, Wang, Yi, Mo, Dan, Ai, Huisheng, Zhang, Jianguo, Guo, Mei, and Qian, Hui
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EXTRACELLULAR vesicles , *TREATMENT effectiveness , *KILLER cells , *CANCER cells , *APOPTOSIS , *KILLER cell receptors , *CELL culture , *PINOCYTOSIS - Abstract
Small extracellular vesicles (sEV) derived from diverse natural killer (NK) cell lines have proven their exceptional antitumor activities. However, sEV from human primary NK cells, especially memory-like NK cells, are rarely utilized for cancer treatment. In this study, we obtained sEV from IL-12, IL-15 and IL-18 cultured human memory-like NK cells (mNK-sEV) that showed strong cytokine-secretory ability. It was uncovered that mNK-sEV entered cancer cells via macropinocytosis and induced cell apoptosis via caspase-dependent pathway. Compared to sEV from conventionally cultured NK cells (conNK-sEV), mNK-sEV inhibited tumor growth to a greater extent. Concomitantly, pharmacokinetics and biodistribution results validated a higher accumulation of mNK-sEV than conNK-sEV in tumors of xenografted murine models. Notably, elevated containment of granulysin (GNLY) within mNK-sEV, at least in part, may contribute to the enhanced therapeutic effect. Herein our results present that mNK-sEV can be a novel class of therapeutic reagent for effective cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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