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: Heleen Dewitte, Sandra Van Lint, Carlo Heirman, Kris Thielemans, Stefaan C De Smedt, Karine Breckpot, Ine Lentacker
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 194 Pg. 28-36 (Nov 28 2014) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 25151979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• RNA, Messenger
• Helium
• trimix
• Nitrogen
• Oxygen

Topics

• Animals
• Antigens, Neoplasm (chemistry)
• Cancer Vaccines (administration & dosage)
• Cell Proliferation (drug effects)
• Dendritic Cells (immunology)
• Helium (chemistry)
• Mice
• Mice, Inbred C57BL
• Microbubbles
• Neoplasms (drug therapy)
• Nitrogen (chemistry)
• Oxygen (chemistry)
• RNA, Messenger (administration & dosage, therapeutic use)
• T-Lymphocytes, Cytotoxic (drug effects)
• Transfection
• Ultrasonics
• Vaccination (methods)