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Design and evaluation of immunotherapeutic imaging for cancer vaccination

Heleen Dewitte (UGent)
(2015)
Author
Promoter
(UGent) , Karine Breckpot and (UGent)
Organization
Abstract
Cancer immunotherapy, where a patient's immune system is harnessed in the battle against a tumor, is currently on the rise. One possible approach comprises the in vitro modulation of dendritic cells with tumor antigens, after which the cells are injected as a therapeutic cancer vaccine. Despite extensive progress and promising (pre)clinical results, such cancer vaccines often remain patient-specific, laborious in production and therefore very expensive. In this thesis, these issues are addressed by developing imageable biomaterials as cancer immunotherapeutics. Firstly, we highlight the use of antigen-loaded perfluorocarbon particles for 19F MRI tracking of dendritic cells is explored. Such imageable cellular vaccines could provide information on the fate and migratory potential of the cells after their injection, and therefore give important initial feedback on the vaccine efficacy. Secondly, we investigated an alternative strategy that makes use of mRNA-loaded microbubbles for ultrasound-guided and ultrasound-triggered immune activation. We demonstrated that this principle could indeed be used to induce antigen expression in dendritic cells in vitro. Moreover, by simultaneously delivering both antigen mRNA and adjuvant mRNA (TriMix), highly immunogenic dendritic cell vaccines could be produced, allowing complete tumor regression in 30% of the vaccinated animals, which were protected against tumor recurrence. Interestingly, these mRNA-loaded microbubbles show potential for the immediate in vivo delivery of mRNA to dendritic cells as they spontaneously migrate to the lymph nodes upon subcutaneous injection. What is more, the image feedback information provided by these contrast agents on the lymphatic anatomy underpins their interesting role as immunotheranostic agents.
Keywords
19F MRI, microbubbles, mRNA, dendritic cells, cancer vaccination, immunotherapy, sonoporation, ultrasound, gene delivery

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Citation

Please use this url to cite or link to this publication:

MLA
Dewitte, Heleen. “Design and Evaluation of Immunotherapeutic Imaging for Cancer Vaccination.” 2015 : n. pag. Print.
APA
Dewitte, H. (2015). Design and evaluation of immunotherapeutic imaging for cancer vaccination. Ghent University. Faculty of Pharmaceutical Sciences ; Vrije Universiteit Brussel. Faculty of Medicine and Pharmacy, Ghent ; Brussels, Belgium.
Chicago author-date
Dewitte, Heleen. 2015. “Design and Evaluation of Immunotherapeutic Imaging for Cancer Vaccination”. Ghent ; Brussels, Belgium: Ghent University. Faculty of Pharmaceutical Sciences ; Vrije Universiteit Brussel. Faculty of Medicine and Pharmacy.
Chicago author-date (all authors)
Dewitte, Heleen. 2015. “Design and Evaluation of Immunotherapeutic Imaging for Cancer Vaccination”. Ghent ; Brussels, Belgium: Ghent University. Faculty of Pharmaceutical Sciences ; Vrije Universiteit Brussel. Faculty of Medicine and Pharmacy.
Vancouver
1.
Dewitte H. Design and evaluation of immunotherapeutic imaging for cancer vaccination. [Ghent ; Brussels, Belgium]: Ghent University. Faculty of Pharmaceutical Sciences ; Vrije Universiteit Brussel. Faculty of Medicine and Pharmacy; 2015.
IEEE
[1]
H. Dewitte, “Design and evaluation of immunotherapeutic imaging for cancer vaccination,” Ghent University. Faculty of Pharmaceutical Sciences ; Vrije Universiteit Brussel. Faculty of Medicine and Pharmacy, Ghent ; Brussels, Belgium, 2015.
@phdthesis{5875557,
  abstract     = {Cancer immunotherapy, where a patient's immune system is harnessed in the battle against a tumor, is currently on the rise. One possible approach comprises the in vitro modulation of dendritic cells with tumor antigens, after which the cells are injected as a therapeutic cancer vaccine. Despite extensive progress and promising (pre)clinical results, such cancer vaccines often remain patient-specific, laborious in production and therefore very expensive. In this thesis, these issues are addressed by developing imageable biomaterials as cancer immunotherapeutics. Firstly, we highlight the use of antigen-loaded perfluorocarbon particles for 19F MRI tracking of dendritic cells is explored. Such imageable cellular vaccines could provide information on the fate and migratory potential of the cells after their injection, and therefore give important initial feedback on the vaccine efficacy. Secondly, we investigated an alternative strategy that makes use of mRNA-loaded microbubbles for ultrasound-guided and ultrasound-triggered immune activation. We demonstrated that this principle could indeed be used to induce antigen expression in dendritic cells in vitro. Moreover, by simultaneously delivering both antigen mRNA and adjuvant mRNA (TriMix), highly immunogenic dendritic cell vaccines could be produced, allowing complete tumor regression in 30% of the vaccinated animals, which were protected against tumor recurrence. Interestingly, these mRNA-loaded microbubbles show potential for the immediate in vivo delivery of mRNA to dendritic cells as they spontaneously migrate to the lymph nodes upon subcutaneous injection. What is more, the image feedback information provided by these contrast agents on the lymphatic anatomy underpins their interesting role as immunotheranostic agents.},
  author       = {Dewitte, Heleen},
  keywords     = {19F MRI,microbubbles,mRNA,dendritic cells,cancer vaccination,immunotherapy,sonoporation,ultrasound,gene delivery},
  language     = {eng},
  pages        = {205},
  publisher    = {Ghent University. Faculty of Pharmaceutical Sciences ; Vrije Universiteit Brussel. Faculty of Medicine and Pharmacy},
  school       = {Ghent University},
  title        = {Design and evaluation of immunotherapeutic imaging for cancer vaccination},
  year         = {2015},
}