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Biomaterials. 2017 May;125:81-89. doi: 10.1016/j.biomaterials.2017.02.019. Epub 2017 Feb 21.

Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination.

Author information

1
Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA; Nanobiointeractions & Nanodiagnostics, Istituto Italiano di Tecnologia (IIT), Via Morego, 30, 16163, Genova, Italy; Università del Salento, Via Provinciale Monteroni, 73100, Lecce, Italy.
2
Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA; Escuela de Ingenieria y Ciencias, Tecnologico de Monterrey, Monterrey, NL, 64849, Mexico.
3
Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
4
Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA; Department of Medicine, Weill Cornell Medical College, 1330 York Ave, New York, NY, 10065, USA.
5
Nanobiointeractions & Nanodiagnostics, Istituto Italiano di Tecnologia (IIT), Via Morego, 30, 16163, Genova, Italy.
6
Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA; Department of Cell and Developmental Biology, Weill Cornell Medical College, 1330 York Ave, New York, NY, 10065, USA. Electronic address: hshen@houstonmethodist.org.

Abstract

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-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene 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-β 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.

KEYWORDS:

Cancer; Immunotherapy; Lipopolyplex; Vaccine; mRNA

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