Receptor crosslinking – A General Method to Trigger Internalisation and Lysosomal Targeting of Therapeutic Receptor: Ligand Complexes

A major unmet clinical need is a universal method for sub-cellular targeting of bioactive molecules to lysosomes. Delivery to this organelle enables either degradation of oncogenic receptors that are overexpressed in cancers, or release of prodrugs from antibody-drug conjugates. Data is available here, which provides evidence that we can achieve targeting of therapeutics and other biological molecules to lysosomes by streptavidin-induced crosslinking. Stacks of images are provided in .tif format, for fluorescently labelled biological proteins that target 3 different membrane proteins (receptors). For each receptor, images are provided for both crosslinking and non-crosslinking conditions. ImageJ and python scripts are included to quantify and display these images, and quantified data is summarised in excel spreadsheets. Western blotting images are provided that demonstrate increased depletion of Her2 under crosslinking conditions. An excel file is provided that describes the experimental conditions for each image stack in the dataset. A published manuscript, with supporting information is included that describes in detail the rationalle behind data: "Receptor crosslinking – A General Method to Trigger Internalisation and Lysosomal Targeting of Therapeutic Receptor:Ligand Complexes".
Research results are published in http://dx.doi.org/10.1038/mt.2015.178