期刊
BIOMATERIALS
卷 125, 期 -, 页码 81-89出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.02.019
关键词
Cancer; Immunotherapy; Lipopolyplex; mRNA; Vaccine
资金
- National Institutes of Health [1R01CA193880-01A1, U54CA210181]
- U.S. Department of Defense [W81XWH-12-1-0414]
- Ernest Cockrell Jr. Distinguished Endowed Chair fund
- Italian Flagship Project NanoMax
- Consejo Nacional de Ciencia y Tecnologia, CONACyT from Mexico
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(beta-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-lamino(poly-ethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell. This core-shell structured mRNA vaccine enters dendritic cells through macropinocytosis. It displayed intrinsic adjuvant activity by potently stimulating interferon-13 and interleukin-12 expression in dendritic cells through Toll-like receptor 7/8 signaling. Dendritic cells treated with the mRNA vaccine displayed enhanced antigen presentation capability. Mice bearing lung metastatic B16-OVA tumors expressing the ovalbumin antigen were treated with the lipopolyplex mRNA, and over 90% reduction of tumor nodules was observed. Collectively, this core-shell structure offers a promising platform for mRNA vaccine development. (C) 2017 Elsevier Ltd. All rights reserved.
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