View in EDS

Enhancement of antitumor potency of extracellular vesicles derived from natural killer cells by IL-15 priming.

Saved in:
Bibliographic Details
Title: Enhancement of antitumor potency of extracellular vesicles derived from natural killer cells by IL-15 priming.
Authors: Zhu, Liya1, Kalimuthu, Senthilkumar1, Oh, Ji Min1, Gangadaran, Prakash1, Baek, Se Hwan1, Jeong, Shin Young1, Lee, Sang-Woo1, Lee, Jaetae1, Ahn, Byeong-Cheol1 abc2000@knu.ac.kr
Source: Biomaterials. Jan2019, Vol. 190, p38-50. 13p.
Subjects: Antineoplastic agents, Extracellular matrix, Vesicles (Cytology), Organelles, Killer cells, Priming (Psychology)
Abstract: Abstract Purpose Natural killer (NK) cells are the key subset of innate-immunity lymphocytes; they possess antitumor activities and are used for cancer immunotherapy. In a previous study, extracellular vehicles (EVs) from NK-92MI cells were isolated and exploited for their ability to kill human cancer cells in vitro and in vivo (multiple injection methods). Here, the potential of NK-cell–derived EVs (NK-EVs) for immunotherapy was improved by priming with interleukin (IL)-15. Methods NK-EVs were isolated from the culture medium without or with IL-15 (NK-EVs IL-15) by ultracentrifugation and were purified via density gradient ultracentrifugation. In addition, NK-EVs and NK-EVs IL-15 were characterized by transmission electron microscopy, nanoparticle-tracking analysis, and western blotting. Flow cytometry, bioluminescence imaging, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed for apoptosis, protein expression, cell proliferation, and cytotoxicity analyses. Furthermore, xenograft tumor–bearing mice were injected with PBS, NK-EVs, or NK-EVs IL-15 intravenously five times. Tumor growth was monitored using calipers and bioluminescence imaging. Toxicity of the nanoparticles was evaluated by measuring the body weight of the mice. Results NK-EVs IL-15 showed significantly higher cytolytic activity toward human cancer cell lines (glioblastoma, breast cancer, and thyroid cancer) and simultaneously increased the expression of molecules associated with NK-cell cytotoxicity. When compared with NK-EVs, NK-EVs IL-15 significantly inhibited the growth of glioblastoma xenograft cells in mice. In addition, both NK-EVs and NK-EVs IL-15 were not significantly toxic to either normal cells or mice. Conclusion IL-15 may improve the immunotherapeutic effects of NK-EVs, thus improving the applications of NK-EVs in the future. [ABSTRACT FROM AUTHOR]
Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
Description
Abstract:Abstract Purpose Natural killer (NK) cells are the key subset of innate-immunity lymphocytes; they possess antitumor activities and are used for cancer immunotherapy. In a previous study, extracellular vehicles (EVs) from NK-92MI cells were isolated and exploited for their ability to kill human cancer cells in vitro and in vivo (multiple injection methods). Here, the potential of NK-cell–derived EVs (NK-EVs) for immunotherapy was improved by priming with interleukin (IL)-15. Methods NK-EVs were isolated from the culture medium without or with IL-15 (NK-EVs IL-15) by ultracentrifugation and were purified via density gradient ultracentrifugation. In addition, NK-EVs and NK-EVs IL-15 were characterized by transmission electron microscopy, nanoparticle-tracking analysis, and western blotting. Flow cytometry, bioluminescence imaging, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed for apoptosis, protein expression, cell proliferation, and cytotoxicity analyses. Furthermore, xenograft tumor–bearing mice were injected with PBS, NK-EVs, or NK-EVs IL-15 intravenously five times. Tumor growth was monitored using calipers and bioluminescence imaging. Toxicity of the nanoparticles was evaluated by measuring the body weight of the mice. Results NK-EVs IL-15 showed significantly higher cytolytic activity toward human cancer cell lines (glioblastoma, breast cancer, and thyroid cancer) and simultaneously increased the expression of molecules associated with NK-cell cytotoxicity. When compared with NK-EVs, NK-EVs IL-15 significantly inhibited the growth of glioblastoma xenograft cells in mice. In addition, both NK-EVs and NK-EVs IL-15 were not significantly toxic to either normal cells or mice. Conclusion IL-15 may improve the immunotherapeutic effects of NK-EVs, thus improving the applications of NK-EVs in the future. [ABSTRACT FROM AUTHOR]
ISSN:01429612
DOI:10.1016/j.biomaterials.2018.10.034