- Universität Zürich > Medizinische Fakultät > Kinderspital Zürich > Infektiologie, Abteilung > Prof. Dr. David Nadal
- Nadal
Current Research Project
- Title / Titel
- TLR9 agonist cancer therapy is rather detrimental than beneficial in EBV-harboring tumors
- Summary / Zusammenfassung
- Multiple phase II and phase III clinical trials using TLR9 agonists as adjuvants for cancer vaccines or conventional chemotherapy have been commenced. TLR9 triggering is regarded as promising strategy to combat cancer, since it induces innate and adaptive immunity. Nevertheless, we have shown that TLR9 triggering results in decreased activation of lytic Epstein-Barr virus (EBV) in primary cells and in EBV-harboring Burkitt’s lymphoma (BL) cells, thus forcing EBV to remain in its potentially oncogenic latent form. This prompts us to hypothesize that cancer therapy with TLR9 agonists is rather detrimental than beneficial for EBV-harboring BL by shutting off lytic EBV. Thus, we will investigate the impact of TLR9 agonists on EBV-harboring cancers using BL Akata cells as a model system. BL Akata cells can be induced to switch EBV from its latent to its lytic form, and we have established clones of Akata cells exhibiting either increased or reduced susceptibility to lytic EBV induction. We will therefore investigate the impact of TLR9 triggering on growth, proliferation, cell cycle, and tumor formation capacity of these BL cells with distinct potential of reactivating EBV in vitro and by using SCID mice xenotransplanted with the distinct BL cells in vivo. For comparison, we will conduct similar investigations using BL BJAB cells which do not harbor EBV and have undergone analogue genetic modifications as their Akata counterparts. This project addresses an utmost important but as yet poorly investigated aspect of the biology and pathogenesis of EBV-harboring BL. The results are essential for assessing the safety of therapies inducing innate immunity for the subset of EBV-harboring cancers.
- Project Leadership and Contacts /
Projektleitung und Kontakte Prof. Dr. med. David Nadal (Project Leader) david.nadal@kispi.uzh.ch
- Funding Source(s) /
Unterstützt durch - Foundation
- Duration of Project / Projektdauer
- Apr 2008 to Sep 2010