title: Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination.
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.
authors.affiliation: 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.
authors.forename: Stefano
authors.initials: S
authors.lastname: Persano
authors.affiliation: 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.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Guevara
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Zhaoqi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Junhua
authors.initials: J
authors.lastname: Mai
authors.affiliation: 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.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Nanobiointeractions & Nanodiagnostics, Istituto Italiano di Tecnologia (IIT), Via Morego, 30, 16163, Genova, Italy.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pompa
authors.affiliation: 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.
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005260:Female; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000008:administration & dosage*; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D008081:Liposomes; D012333:RNA, Messenger
keywords: Cancer; Immunotherapy; Lipopolyplex; Vaccine; mRNA