Sandra Diebold, Dr. rer. nat.
Division of Immunology, Infection and Inflammatory Disease
Tel: +44(0)20 7188 1181
Our background is in viral recognition by dendritic cells and we have studied dendritic cell activation via several pattern recognition receptors in the past. The main viral pathogen-associated molecular patterns that are recognised by the innate immune system are viral nucleic acids and there are cytoplasmic and endosomal pattern recognition receptors with the ability to sense viral single-stranded RNA, viral double-stranded RNA and viral DNA. Dendritic cells are not the only cells expressing these pattern recognition receptors, but because of their crucial role in the instruction of adaptive immune responses, the mechanisms of their activation is of particular importance.
We have an interest in developing new vaccination approaches for tumour immunotherapy. Tumours can express tumour-associated antigens that are recognized by the adaptive immune system. Nevertheless, tumour cells are poor inducers of immune responses since they lack stimuli such as pathogen-associated molecular patterns that efficiently activate the innate immune system. Viral nucleic acids represent ideal, molecularly defined adjuvants to promote the induction of effective anti-tumour immune responses. Therefore, we explore the application of synthetic mimics of viral nucleic acids as adjuvants in the context of tumour immunotherapy. We study various vaccine approaches employing mimics of viral nucleic acids as adjuvants such as dendritic cell vaccines, tumour cell vaccines and direct targeting of dendritic cells in vivo. These different vaccination approaches are studied in vivo in mouse models and results are confirmed in vitro with human dendritic cells
Carlin, L. M., Stamatiades, E. G., Auffray, C., Hanna, R. N., Glover, L., Vizcay-Barrena, G., Hedrick, C. C., Cook, H. T., Diebold, S. S. and Geissmann, F. (2013). Nr4a1-dependent Ly6Clow monocytes monitor endothelial cells and orchestrate their disposal. Cell 153, 362-375.
Kreutz, M., Giquel, B., Hu, Q., Abuknesha, R., Uematsu, S., Akira, S., Nestle, F.O. and Diebold, S.S. (2012). Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity. PLoS ONE 7(7): e40208.
Tavaré R, Sagoo P, Varama G, Tanriver Y, Warely A, Diebold SS, Southworth R, Schaeffter T, Lechler RI, Razavi R, Lombardi G, Mullen GE. (2011). Monitoring of in vivo function of superparamagnetic iron oxide labelled murine dendritic cells during anti-tumour vaccination. PLoS One 6(5):e19662.
Rajagopal D, Paturel C, Morel Y, Uematsu S, Akira S, Diebold SS. (2010). Plasmacytoid dendritic cell-derived type I interferon is crucial for the adjuvant activity of Toll-like receptor 7 agonists. Blood 115, 1949-1957.
Brencicova, E., and Diebold, S. S. (2013). Nucleic acids and endosomal pattern recognition: how to tell friend from foe? Front. Cell. Infect. Microbiol. 3:37, 1-14.