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Project

Interleukin-15 transpresentation and silencing of programmed-death ligands as attractive strategies in the optimization of a new generation therapeutic vaccines against leukemia.

Dendritic cell (DC)-based cancer vaccines have been shown to be safe and well tolerated. Although there is a growing body of evidence that DC-based vaccination can be of clinical benefit, there is still room for improvement to enhance the potency and efficacy of the currently used DC vaccine preparations. In this context, new DC generation protocols that boost their immunogenic properties may provide an improved clinical benefit by a more powerful activation of T cells and natural killer (NK) cells, which could then optimally control or eliminate residual cancer cells. Therefore, a novel monocyte-derived DC generation protocol is being developed in vitro in this study focusing on two different strategies. First, conventional monocyte-derived IL 4 DC are being modified to express interleukin (IL )15 on their membrane by using IL-15 and IL 15Rα mRNA electroporation. I have shown that IL-15 can enhance the antitumor capacity of DC (Van den Bergh et al, J Cell Mol Med 2014) and that the IL-15/IL-15Rα-expressing designer DC have an improved capacity to activate NK cells (Van den Bergh et al, Oncotarget 2015). Now, I will investigate if this strategy also results in improved T cell activation. As a second innovation, the expression of programmed death ligands 1 and 2 (PD-L1 and PD-L2) will be inhibited, since both IL-15 and PD-L-silencing might be able to increase the antigen-specific T cell-stimulatory properties of the DC. To test this, the ability of the DC will be examined to induce or enhance the proliferation, degranulation, cytokine-producing capacity and cytotoxic profile of antigen-specific T cells. Overall, this study will generate valuable new insights into approaches to improve clinical outcome of DC-based cancer immunotherapy.
Date:1 Jan 2017 →  30 Jun 2017
Keywords:LEUKEMIA
Disciplines:Morphological sciences, Oncology