作者
Yining Zhu, Jingyao Ma, Ruochen Shen, Jinghan Lin, Shuyi Li, Xiaoya Lu, Jessica L Stelzel, Jiayuan Kong, Leonardo Cheng, Ivan Vuong, Zhi-Cheng Yao, Christine Wei, Nicole M Korinetz, Wu Han Toh, Joseph Choy, Rebekah A Reynolds, Melanie J Shears, Won June Cho, Natalie K Livingston, Gregory P Howard, Yizong Hu, Stephany Y Tzeng, Donald J Zack, Jordan J Green, Lei Zheng, Joshua C Doloff, Jonathan P Schneck, Sashank K Reddy, Sean C Murphy, Hai-Quan Mao
发表日期
2023/12/11
期刊
Nature biomedical engineering
页码范围
1-17
出版商
Nature Publishing Group UK
简介
Lipid nanoparticles (LNPs) can be designed to potentiate cancer immunotherapy by promoting their uptake by antigen-presenting cells, stimulating the maturation of these cells and modulating the activity of adjuvants. Here we report an LNP-screening method for the optimization of the type of helper lipid and of lipid-component ratios to enhance the delivery of tumour-antigen-encoding mRNA to dendritic cells and their immune-activation profile towards enhanced antitumour activity. The method involves screening for LNPs that enhance the maturation of bone-marrow-derived dendritic cells and antigen presentation in vitro, followed by assessing immune activation and tumour-growth suppression in a mouse model of melanoma after subcutaneous or intramuscular delivery of the LNPs. We found that the most potent antitumour activity, especially when combined with immune checkpoint inhibitors, resulted from a …
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