title: Intranasal mRNA nanoparticle vaccination induces prophylactic and therapeutic anti-tumor immunity.
abstract: Direct in vivo administration of messenger RNA (mRNA) delivered in both naked and nanoparticle formats are actively investigated because the use of dendritic cells transfected ex vivo with mRNA for cancer therapy is expensive and needs significant infrastructure. Notably, intravenous and subcutaneous injections are the only routes of administration tested for mRNA nanoparticle tumor vaccination. In this report, we demonstrate that tumor immunity can be achieved via nasal administration of mRNA. Mice nasally immunized with mRNA delivered in nanoparticle format demonstrate delayed tumor progression in both prophylactic and therapeutic immunization models. The observed tumor immunity correlates with splenic antigen-specific CD8+ T cells and is achieved only when mRNA is delivered in nanoparticle but not in naked format. In conclusion, we demonstrate, as a proof-of-concept, a non-invasive approach to mRNA tumor vaccination, increasing its potential as a broadly applicable and off-the-shelf therapy for cancer treatment.
authors.affiliation: 1] Department of Biomedical Engineering, Duke University, USA [2] Department of Chemical & Biomolecular Engineering, National University of Singapore, Singapore.
authors.forename: Kyle K L
authors.initials: KK
authors.lastname: Phua
authors.affiliation: Department of Pathology, Duke University Medical Center, USA.
authors.forename: Herman F
authors.initials: HF
authors.lastname: Staats
authors.affiliation: 1] Department of Biomedical Engineering, Duke University, USA [2] Department of Surgery, Duke University Medical Center, USA.
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
authors.affiliation: Department of Surgery, Duke University Medical Center, USA.
authors.forename: Smita K
authors.initials: SK
authors.lastname: Nair
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D004339:Drug Compounding / Q000379:methods; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D012333:RNA, Messenger