title: In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer.
abstract: Nanotechnology has tremendous potential to contribute to cancer immunotherapy. The 'in situ vaccination' immunotherapy strategy directly manipulates identified tumours to overcome local tumour-mediated immunosuppression and subsequently stimulates systemic antitumour immunity to treat metastases. We show that inhalation of self-assembling virus-like nanoparticles from cowpea mosaic virus (CPMV) reduces established B16F10 lung melanoma and simultaneously generates potent systemic antitumour immunity against poorly immunogenic B16F10 in the skin. Full efficacy required Il-12, Ifn-γ, adaptive immunity and neutrophils. Inhaled CPMV nanoparticles were rapidly taken up by and activated neutrophils in the tumour microenvironment as an important part of the antitumour immune response. CPMV also exhibited clear treatment efficacy and systemic antitumour immunity in ovarian, colon, and breast tumour models in multiple anatomic locations. CPMV nanoparticles are stable, nontoxic, modifiable with drugs and antigens, and their nanomanufacture is highly scalable. These properties, combined with their inherent immunogenicity and demonstrated efficacy against a poorly immunogenic tumour, make CPMV an attractive and novel immunotherapy against metastatic cancer.
authors.affiliation: Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Lizotte
authors.affiliation: Biomedical Engineering, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Wen
authors.affiliation: Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Sheen
authors.affiliation: Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.
authors.forename: J
authors.initials: J
authors.lastname: Fields
authors.affiliation: Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.
authors.forename: P
authors.initials: P
authors.lastname: Rojanasopondist
authors.affiliation: Biomedical Engineering, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.|Department of Radiology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.|Department of Materials Science and Engineering, Case School of Engineering, Cleveland, Ohio 44106, USA.|Department of Macromolecular Science and Engineering, Case School of Engineering, Cleveland, Ohio 44106, USA.|Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: N F
authors.initials: NF
authors.lastname: Steinmetz
authors.affiliation: Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.|Department of Genetics, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.|Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA.
authors.forename: S
authors.initials: S
authors.lastname: Fiering
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D017798:Comovirus / Q000737:chemistry*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods; D014765:Viral Vaccines / Q000008:administration & dosage
chemical_list: D019496:Cancer Vaccines; D014765:Viral Vaccines