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Liposomes loaded with a STING pathway ligand, cyclic di-GMP, enhance cancer immunotherapy against metastatic melanoma
This item is licensed under:Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
| Title: | Liposomes loaded with a STING pathway ligand, cyclic di-GMP, enhance cancer immunotherapy against metastatic melanoma |
| Authors: | Nakamura, Takashi Browse this author →KAKEN DB | | Miyabe, Hiroko Browse this author | | Hyodo, Mamoru Browse this author →KAKEN DB | | Sato, Yusuke Browse this author →KAKEN DB | | Hayakawa, Yoshihiro Browse this author →KAKEN DB | | Harashima, Hideyoshi Browse this author →KAKEN DB |
| Keywords: | STING | | c-di-GMP | | Liposome | | Adjuvant | | Melanoma | | Cancer immunotherapy |
| Issue Date: | 28-Oct-2015 |
| Publisher: | Elsevier |
| Journal Title: | Journal of controlled release |
| Volume: | 216 |
| Start Page: | 149 |
| End Page: | 157 |
| Publisher DOI: | 10.1016/j.jconrel.2015.08.026 |
| PMID: | 26282097 |
| Abstract: | Malignant melanomas escape immunosurveillance via the loss/down-regulation of MHC-I expression. Natural killer (NK) cells have the potential to function as essential effector cells for eliminating melanomas. Cyclic di-GMP (c-di-GMP), a ligand of the stimulator of interferon genes (STING) signal pathway, can be thought of as a new class of adjuvant against cancer. However, it is yet to be tested, because technologies for delivering c-di-GMP to the cytosol are required. Herein, we report that c-di-GMP efficiently activates NK cells and induces antitumor effects against malignant melanomas when loaded in YSK05 lipid containing liposomes, by assisting in the efficient delivery of c-di-GMP to the cytosol. The intravenous administration of c-di-GMP encapsulated with-in YSK05-liposomes (c-di-GMP/YSK05-Lip) into mice efficiently induced the production of type I interferon (IFN) as well as the activation of NK cells, resulting in a significant antitumor effect in a lung metastasis mouse model using B16-F10. This antitumor effect was dominated by NK cells. The infiltration of NK cells was observed in the lungs with B16-F10 melanomas. These findings indicate that the c-di-GMP/YSK05-Lip induces MHC-I nonrestricted antitumor immunity mediated by NK cells. Consequently, c-di-GMP/YSK05-Lip represents a potentially new adjuvant system for use in immunotherapy against malignant melanomas. (C) 2015 Elsevier B.V. All rights reserved. |
| Rights: | © 2015, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/63312 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 中村 孝司
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