title: The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy.
abstract: Dendritic cell (DC)-based cancer vaccines, where the patient's own immune system is harnessed to target and destroy tumor tissue, have emerged as a potent therapeutic strategy. In the development of such DC vaccines, it is crucial to load the DCs with tumor antigens, and to simultaneously activate them to become more potent antigen-presenting cells. For this, we report on microbubbles, loaded with both antigen mRNA as well as immunomodulating TriMix mRNA, which can be used for the ultrasound-triggered transfection of DCs. In vivo experiments with in vitro sonoporated DCs show the effective induction of antigen-specific T cells, resulting in specific lysis of antigen-expressing cells. Especially in a therapeutic setting, sonoporation with TriMix has an important added value, resulting in a significant reduction of tumor outgrowth and a marked increase in overall survival. What is more, complete tumor regression was observed in 30% of the antigen+TriMix DC vaccinated animals, which also displayed long-term antigen-specific immunological memory. As a result, DC sonoporation using microbubbles loaded with a combination of antigen and TriMix mRNA can elicit powerful immune responses in vivo, and might serve as a potential tool for further in vivo DC vaccination applications.
authors.affiliation: Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: Heleen.Dewitte@UGent.be.
authors.forename: Heleen
authors.initials: H
authors.lastname: Dewitte
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Department of Biomedical Sciences, Medical School of the Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1050 Jette, Belgium. Electronic address: sandra.van.lint@vub.ac.be.
authors.forename: Sandra
authors.initials: S
authors.lastname: Van Lint
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Department of Biomedical Sciences, Medical School of the Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1050 Jette, Belgium. Electronic address: carlo.heirman@vub.ac.be.
authors.forename: Carlo
authors.initials: C
authors.lastname: Heirman
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Department of Biomedical Sciences, Medical School of the Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1050 Jette, Belgium. Electronic address: Kris.Thielemans@vub.ac.be.
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.affiliation: Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: Stefaan.DeSmedt@UGent.be.
authors.forename: Stefaan C
authors.initials: SC
authors.lastname: De Smedt
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Department of Biomedical Sciences, Medical School of the Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1050 Jette, Belgium. Electronic address: karine.breckpot@vub.ac.be.
authors.forename: Karine
authors.initials: K
authors.lastname: Breckpot
authors.affiliation: Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: Ine.Lentacker@UGent.be.
authors.forename: Ine
authors.initials: I
authors.lastname: Lentacker
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology*; D006371:Helium / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D009369:Neoplasms / Q000188:drug therapy*; D009584:Nitrogen / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014162:Transfection; D014465:Ultrasonics; D014611:Vaccination / Q000379:methods
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D012333:RNA, Messenger; D006371:Helium; C045257:trimix; D009584:Nitrogen; D010100:Oxygen
keywords: CFSE (PubChem CID: 16211581); Cancer vaccination; DOPE (PubChem CID: 9546757); DOTAP (PubChem CID: 6437371); Dendritic cell; Immune modulation; Microbubble; SIINFEKL (PubChem CID: 71311993); Sonoporation; mRNA