mRNA based immunotherapy of melanoma

Project Details

Description

Introduction: Researchers have focused on using the body's own immune system to tackle cancer cells, as this approach offers the promise of an effective non-toxic therapy. One strategy to educate T cells so as they destroy cancer cells, is the use of dendritic cells (DCs), the professional antigen-presenting cells of our immune system. Therefore, DCs need to be loaded with cancer antigens and need to be productively activated.
Previous research results: In the pursuit of an optimal DC vaccine we have developed mRNA electroporation of DCs to deliver not only cancer antigens, but also molecules necessary to enhance the T cell stimulatory potential of DCs (CD40Ligand, a constitutive active form of toll like receptor 4 and CD70, TriMix) (Bonehill 2008).
These TriMix-DCs were shown to be effective in treatment of melanoma (Bonehill 2009. Because this strategy is patient-specific, time and money consuming we now want to focus on in situ modification of DCs. This could provide a strategy for a much simplified maintenance therapy. Aim and preliminary data: We propose to evaluate the use of mRNA to modify DCs in situ in order to boost anti-cancer immune responses. To proof the feasibility of this strategy we first demonstrated that mRNA, which is injected in the lymph node or tumor is specifically taken up and translated by DCs. Moreover, we demonstrated that delivery of antigen mRNA and TriMix in the lymph node elicits strong antigenspecific CTL responses. These data are now translated in a human setting. Conclusion: Our preliminary data demonstrating the possibility to specifically target DCs in vivo together with the fact that mRNA has many advantages (off-the-shelf, safe, easy to produce, inexpensive) warrant an in depth evaluation and comparison of the mRNA-based vaccination strategy to DC vaccination.
AcronymFWOAL649
StatusFinished
Effective start/end date1/01/1231/12/15

Keywords

  • Tonic Pain
  • Dendritic Cells
  • Evoked Potentials
  • Bispecific Antibodies
  • Immunotherapy
  • Immunology
  • Oncology

Flemish discipline codes

  • Basic sciences
  • Biological sciences
  • Materials engineering