Therapeutic effect of small extracellular vesicles from cytokine-induced memory-like natural killer cells on solid tumors

• Published in: Journal of nanobiotechnology Vol. 22; no. 1; pp. 447 - 17
• Main Authors: Shi, Yinghong, Chen, Yanxia, Wang, Yi, Mo, Dan, Ai, Huisheng, Zhang, Jianguo, Guo, Mei, Qian, Hui
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29.07.2024; BioMed Central; BMC
• Subjects: Analysis; Animals; Antigens; Antigens, Differentiation, T-Lymphocyte; Apoptosis; Apoptosis - drug effects; B cells; Cancer; Cancer therapy; Care and treatment; Cell Line, Tumor; Chemical tests and reagents; Comparative analysis; Cytokines; Cytokines - metabolism; Cytotoxicity; Diagnosis; Extracellular Vesicles - metabolism; Female; Granulysin; Health aspects; Humans; Killer cells; Killer Cells, Natural - drug effects; Memory-like natural killer cells; Mice; Mice, Inbred BALB C; Neoplasms - drug therapy; Pinocytosis - drug effects; Small extracellular vesicle; Testing; Tissue Distribution; Tumors; Xenograft Model Antitumor Assays; China; Memory-like natural killer cells; Cytotoxicity; Cancer therapy; Granulysin; Small extracellular vesicle
• DOI: 10.1186/s12951-024-02676-1
• ISSN: 1477-3155

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.