Dectin-1 Research – Prof Gordon Brown
- Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town
- Email: firstname.lastname@example.org
Title of the project
Role of Dectin-1 in beta-glucan mediated anti-cancer immunotherapy (Project ended 31 March 2009)
Highlights of the Project
We have made significant findings:
- We have fully characterized the Dectin-1 knockout mice, which has resulted in a publication in Nature Immunology and in the Journal of Immunology.
- We have determined the signalling mechanism by which beta-glucans mediate their immuno-modulatory activity in vitro. This work has been published in two papers in theEuropean Journal of Immunology.
- We have demonstrated that beta-glucans can drive anti-cancer responses through Dectin-1. This work was published in Blood.
How was the project of value in the struggle against cancer?
The use of monoclonal antibodies as immunotherapeutic agents for specific cancers is now an accepted clinical practice, although the mechanisms behind their beneficial effects are not fully understood. One mechanism involves complement-mediated cytotoxicity, whereby the monoclonal antibody induces complement deposition on the targeted cancer cells, leading to the stimulation of complement receptor 3 (CR3)-dependent leukocyte killing of the tumour cells. Triggering of this cytotoxicity, however, requires a second stimulus, such as that mediated by β-glucan carbohydrates, leading to proposals that these carbohydrates could be used as adjuvants for these treatments. β-Glucans can also directly potentiate host protective responses against cancer and there have been a number of clinical trials using these carbohydrates with promising results. Our project is laying the foundation for a better understanding of the molecular mechanisms by which β-glucans exert their anti-cancer effects, which will present novel therapeutic strategies for the treatment of cancer in the future.
- Faro-Trindade, I and G.D. Brown. Interaction of Candida albicans with phagocytes. In Russell, D.G. and S. Gordon (ed.), The Multiple Faces Of The Phagocyte. American Society for Microbiology, Washington, D.C. In Press. Click here to read the abstract on PubMed.
- Brown, G.D. and D.L. Williams. (1,3)-β-Glucans in innate immunity: Mammalian systems. In, Bacic, A., Fincher, G.B., and B.A. Stone (eds). Chemistry, biochemistry and biology of (1→3)-β-glucans & related polysaccharides. Chapter 4.5.2. Elsevier. In Press. Click here to read the publication (0.269166 MB)
- Werner, J.L., Metz, A.E., Horn, D., Schoeb, T.R., Hewitt, M.M., Schwiebert, L.M., Faro-Trindade, I., Brown, G.D., and C. Steele. Requisite role for the Dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus. The Journal of Immunology. In Press. Click here to read the abstract on PubMed.
- Dennehy, K.M., Willment, J.A., Williams, D.L., and G. D. Brown. Reciprocal regulation of IL-23 and IL-12 following co-activation of Dectin-1 and Toll-like receptor signaling pathways. European Journal of Immunology. In Press. Click here to read the publication (0.163754 MB)
- LeibundGut-Landmann, S., Osorio, F., Brown, G.D., Reis e Sousa, C. 2008.Stimulation of dendritic cells via the Dectin-1 / Syk pathway allows priming of cytotoxic T cell responses. Blood. 112:4971-80
- Dennehy, K.M., Ferwerda, G., et al and G.D. Brown. 2008. Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors.European Journal of Immunology. 38:500-6. Click here to read the publication (0.255079 MB)
- Willment, J.A. and G.D. Brown. 2008. C-type lectin receptors in anti-fungal immunity.Trends Microbiol. 16:27-32
- Taylor, P.R., Tsoni, S.V., Willment, J.A., Dennehy, K.M., Rosas, M., Findon, H., Haynes, K., Steele, C., Botto, M., Gordon, S. and G. D. Brown. 2007. A critical role for β-glucan recognition in the control of fungal infection. Nature Immunology. 8:31-38. Click here to read the publication (0.485332 MB)
- Dectin-1 Research