ASPIRE: adjuvant-driven induction of cancer Specific Immune Responses

Student thesis: Doctoral Thesis

Abstract

Our immune system can detect and destroy cancer cells. Nonetheless, some people still develop cancer, because growing cancer cells camouflage themselves as well as possible, blocking the attack of the immune system, or worse, they hijack certain cells of the immune system and turn them into cancer promoting cells. In an attempt to stop this process, scientists want to boost the immune system. This can be done through cancer immunization a.k.a. vaccination. The rationale is to provide the immune system with; (i) the identification card of cancer cells, tumor antigens as well as (ii) adjuvants, which serve as a wake-up call to alarm the immune system of the invading enemy, the cancer cells. Several cancer vaccination strategies have been developed, among which the use of cells engineered in the laboratory. Although promising so-called ex vivo engineered cell-based vaccines are patient-specific and therefore time and money consuming. To generate a widely applicable cancer vaccine, it is important to immediately activate the immune cells in the patient's body. In this regard, mRNA the chemical blueprint for protein production has shown great promise. Therefore, in this PhD project we evaluated two strategies to exploit mRNA for cancer immunization. We showed that mRNA can be delivered to cells in the tumor, and that mRNA encoding a potent adjuvant can boost the immune system, while incapacitating tumor-promoting cells. Moreover we evaluated lipid-based nanoparticles to deliver mRNA to cells systemically, showing activation of the immune system in part due to the inherent adjuvant-activity of the mRNA. As such we have set the first steps on a path to a widely applicable vaccination strategy.
Date of Award20 Oct 2016
Original languageEnglish
Awarding Institution
  • Vrije Universiteit Brussel
SupervisorKarine Breckpot (Promotor), Kris Thielemans (Promotor), Karin Vanderkerken (Jury), Leo van Grunsven (Jury), Eline Menu (Jury), Koen Van Raemdonck (Jury) & Steve Pascolo (Jury)

Keywords

  • immune system
  • cancer cells
  • vaccination

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