Targeted LNPs deliver IL-15 superagonists mRNA for precision cancer therapy

被引:0
|
作者
Yu, Juntao [1 ]
Li, Qian [2 ]
Zhang, Chaoting [4 ]
Wang, Qiu [2 ]
Luo, Shenggen [1 ]
Wang, Xiaona [1 ]
Hu, Rongkuan [1 ]
Cheng, Qiang [2 ,3 ]
机构
[1] Starna Therapeut Co Ltd, Suzhou 215123, Peoples R China
[2] Peking Univ, Coll Future Technol, Dept Biomed Engn, Beijing 100871, Peoples R China
[3] Peking Univ, Beijing Adv Ctr RNA Biol BEACON, Beijing 100871, Peoples R China
[4] Peking Univ Canc Hosp & Inst, Minist Educ Beijing, Lab Biochem & Mol Biol,, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China
关键词
IL-15; superagonists; mRNA delivery; Lipid nanoparticles; Lung-targeting; Cytokine therapy; INTERLEUKIN-15; COMPLEX; BIOLOGY; PROLIFERATION; CELLS;
D O I
10.1016/j.biomaterials.2024.123047
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Interleukin-15 (IL-15) emerges as a promising immunotherapeutic candidate, but the therapeutic utility remains concern due to the unexpected systematic stress. Here, we propose that the mRNA lipid nanoparticle (mRNALNP) system can balance the issue through targeted delivery to increase IL-15 concentration in the tumor area and reduce leakage into the circulation. In the established Structure-driven TARgeting (STAR) platform, the LNPLocal and LNPLung can effectively and selectively deliver optimized IL-15 superagonists mRNAs to local and lungs, respectively, in relevant tumor models. As a result, such superagonists exhibited well-balanced efficacy and side-effects, demonstrating the better anti-tumor activity, less systematic exposure, and less cytokine related risks. We finally verified the selective delivery and well tolerability of LNPLung in non-human primates (NHPs), confirming the potential for clinical application. This finding provides new potentials for cancers treatment on lung cancers or lung metastasis cancers.
引用
收藏
页数:11
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