標題: Combination of fucoidan-based magnetic nanoparticles and immunomodulators enhances tumour-localized immunotherapy
作者: Chiang, Chih-Sheng
Lin, Yu-Jung
Lee, Rachel
Lai, Yen-Ho
Cheng, Hung-Wei
Hsieh, Chia-Hung
Shyu, Woei-Cherng
Chen, San-Yuan
交大名義發表
材料科學與工程學系
National Chiao Tung University
Department of Materials Science and Engineering
公開日期: 1-Aug-2018
摘要: Checkpoint immunotherapy that inhibits tumour immune evasion has demonstrated significant clinical success. However, the therapeutic response is limited to certain patient populations, and immunotoxicity as well as autoimmunity have compromised the therapeutic benefits. Here, we report on an inherently therapeutic fucoidan-dextran-based magnetic nanomedicine (IO@FuDex(3)) conjugated with a checkpoint inhibitor (anti-PD-L1) and T-cell activators (anti-CD3 and anti-CD28). IO@FuDex(3 )can repair the immunosuppressive tumour microenvironment by reinvigorating tumour-infiltrating lymphocytes, while targeting the nanomedicine via magnetic navigation to the tumour to minimize off-target effects. Treatment that combines IO@FuDex(3) and magnetic navigation reduces the occurrence of adverse events and extends the median survival from 32 to 63 days with less than 1per cent dose compared with soluble anti-PD-L1. Thus, we demonstrate the potential of integrating anti-PD-L1 and T-cell activators as a form of inherently therapeutic nanomedicine to augment the therapeutic index of combination checkpoint immunotherapy.
URI: http://dx.doi.org/10.1038/s41565-018-0146-7
http://hdl.handle.net/11536/147962
ISSN: 1748-3387
DOI: 10.1038/s41565-018-0146-7
期刊: NATURE NANOTECHNOLOGY
Volume: 13
起始頁: 746
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