The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy
The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy
复制标题
DOI：
10.1016/j.jconrel.2014.08.011
复制
发表时间：
2014-11-28
影响因子：
10.8
通讯作者：
Lentacker, Ine
中科院分区：
文献类型：
--
作者：
Dewitte, Heleen;Van Lint, Sandra;Lentacker, Ine
树突状细胞（DC）为基础的癌症疫苗，其中患者自身的免疫系统被利用来靶向和破坏肿瘤组织，已成为一种有效的治疗策略。在这种DC疫苗的开发中，至关重要的是用肿瘤抗原加载DC，并同时激活它们以成为更有效的抗原呈递细胞。为此，我们报告了微泡，装载抗原mRNA以及免疫调节TriMix mRNA，可用于超声触发的DC转染。体外声穿孔DC的体内实验显示抗原特异性T细胞的有效诱导，导致抗原表达细胞的特异性裂解。特别是在治疗环境中，TriMix声致穿孔具有重要的附加价值，可显著减少肿瘤生长，显著增加总生存期。此外，在30%的抗原+ TriMix DC疫苗接种的动物中观察到完全肿瘤消退，其也显示出长期抗原特异性免疫记忆。因此，使用负载有抗原和TriMix mRNA的组合的微泡的DC声致穿孔可以在体内引发强大的免疫应答，并且可以用作进一步体内DC疫苗接种应用的潜在工具。(C)2014爱思唯尔有限公司版权所有。
Dendritic cell (DC)-based cancer vaccines, where the patient's own immune system is harnessed to target and destroy tumor tissue, have emerged as a potent therapeutic strategy. In the development of such DC vaccines, it is crucial to load the DCs with tumor antigens, and to simultaneously activate them to become more potent antigen-presenting cells. For this, we report on microbubbles, loaded with both antigen mRNA as well as immunomodulating TriMix mRNA, which can be used for the ultrasound-triggered transfection of DCs. In vivo experiments with in vitro sonoporated DCs show the effective induction of antigen-specific T cells, resulting in specific lysis of antigen-expressing cells. Especially in a therapeutic setting, sonoporation with TriMix has an important added value, resulting in a significant reduction of tumor outgrowth and a marked increase in overall survival. What is more, complete tumor regression was observed in 30% of the antigen + TriMix DC vaccinated animals, which also displayed long-term antigen-specific immunological memory. As a result, DC sonoporation using microbubbles loaded with a combination of antigen and TriMix mRNA can elicit powerful immune responses in vivo, and might serve as a potential tool for further in vivo DC vaccination applications. (C) 2014 Elsevier B.V. All rights reserved.