Frauke Koenig, a PhD student in Professor Christoph Bräuchle'd group, in the Department of Physical Chemistry at the Ludwig Maximilians University (LMU) Munich, was awarded this year's Society for Experimental Biology and Medicine European Prize for her work on live cell imaging of EGFR receptor targeting with short synthetic peptides. This multidisciplinary study was performed in collaboration with Professor Christoph Bräuchle, Professor Ernst Wagner and Dr Manfred Oris's groups in the departments of Physical chemistry and Pharmacy at LMU.
The work selected for oral presentation was described at the 2010 Annual Conference of the German society for Gene Therapy, held in October in Munich. In this study live-cell imaging experiments were used to examine cellular internalization and trafficking of artificial gene vectors carrying a short peptide ligand, GE11, for specific targeting of EGF receptor positive cells.
Frauke Koenig said "EGF receptor is a promising target for selective gene therapy of cancer cells as it is overexpressed in many human tumors. Previous studies have shown that full-length EGF can be coupled to artificial gene vectors, such as polyplexes, resulting in their fast endocytosis into cancer cells. However full-length EGF has limitations for clinical application, as it is expensive in production, has a high tendency to aggregate and most importantly is able to activate the EGFR mediated mitogenic signaling cascades in the target cells. In this study polyplexes displaying GE11, a short peptide ligand with high affinity for the EGF receptor, provided a potential alternative for targeted cancer therapy. Highly sensitive fluorescence microscopy with high spatial and temporal resolution was employed to follow the cellular internalization of single polyplexes in real time". The presented data demonstrated slower kinetics of internalization for GE11 polyplexes, compared to EGF polyplexes. However, GE11 polyplexes provided considerable advantages for clinical applications, including higher transduction efficiency, lower aggregation and reduced mitogenic activity."
Presenting the award on behalf of the Society for Experimental Biology and Medicine, Professor Farzin Farzaneh (European Editor of Experimental Biology and Medicine), pointed out the therapeutic potential of receptor targeting not just for the tumor specific delivery of genes but also other therapeutic applications. This study also demonstrates the tremendous potential of live cell imaging as a tool for screening of candidate molecules for detailed analysis of molecular interactions and the identification of new drugs. The panel of Judges commended Ms Koenig for her outstanding work, its clear presentation and the stimulating discussion of broader implications of this study.
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