细胞毒性T细胞
免疫系统
佐剂
癌症免疫疗法
抗原
免疫疗法
癌症疫苗
细胞内
T细胞
生物
癌症研究
化学
免疫学
细胞生物学
体外
生物化学
作者
Matthias A. Oberli,Andreas M. Reichmuth,J. Robert Dorkin,Michael J. Mitchell,Owen S. Fenton,Ana Jaklenec,Daniel G. Anderson,Robert Langer,Daniel Blankschtein
出处
期刊:Nano Letters
[American Chemical Society]
日期:2016-12-05
卷期号:17 (3): 1326-1335
被引量:490
标识
DOI:10.1021/acs.nanolett.6b03329
摘要
The induction of a strong cytotoxic T cell response is an important prerequisite for successful immunotherapy against many viral diseases and tumors. Nucleotide vaccines, including mRNA vaccines with their intracellular antigen synthesis, have been shown to be potent activators of a cytotoxic immune response. The intracellular delivery of mRNA vaccines to the cytosol of antigen presenting immune cells is still not sufficiently well understood. Here, we report on the development of a lipid nanoparticle formulation for the delivery of mRNA vaccines to induce a cytotoxic CD 8 T cell response. We show transfection of dendritic cells, macrophages, and neutrophils. The efficacy of the vaccine was tested in an aggressive B16F10 melanoma model. We found a strong CD 8 T cell activation after a single immunization. Treatment of B16F10 melanoma tumors with lipid nanoparticles containing mRNA coding for the tumor-associated antigens gp100 and TRP2 resulted in tumor shrinkage and extended the overall survival of the treated mice. The immune response can be further increased by the incorporation of the adjuvant LPS. In conclusion, the lipid nanoparticle formulation presented here is a promising vector for mRNA vaccine delivery, one that is capable of inducing a strong cytotoxic T cell response. Further optimization, including the incorporation of different adjuvants, will likely enhance the potency of the vaccine.
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