Project description
Profiling extracellular proteases supports protease-based diagnostics and targeted tumour therapies
Proteases are enzymes, themselves proteins, that cleave or break down other proteins. They have essential functions in the healthy body. Some extracellular proteases also play a key role in tumour progression. Monitoring protease activity in vivo would support diagnostics, prognostics and therapeutics, yet it is very difficult to do with high sensitivity and selectivity. The EU-funded PROTECT project will tackle this challenge with a unique and comprehensive platform for diagnostics and personalised cancer therapy. It will enable monitoring of protease activity, leading to tumour specific protease profiles and targeted release of drugs.
Objective
Proteases are involved in all hallmarks of cancer and are key regulators of tumor progression. The difficulties to monitor protease activity in vivo with sufficient sensitivity and selectivity make development of protease targeting cancer drugs and implementation of protease activity as a diagnostic and prognostic biomarker very challenging. The aim of PROTECT is to develop a novel comprehensive protease activity profiling platform for cancer-associated extracellular proteases that can address the main limitations of current strategies for in vivo protease activity monitoring with the ambition to enable a dramatic increase in sensitivity and multiplexing capabilities. We will design Liposomal Activity-Based Sensors (LABS) that can amplify proteolytic cleavage by triggering release of liposome encapsulated synthetic biomarkers. We will further leverage the possibilities to extract tumor specific protease profiles for development of personalized protease-triggered liposomal drug delivery vehicles (PROVES) for precision medicine. Sophisticated protease-responsive membrane active peptides (proMAPs) will be developed to couple protease activity to biomarker and drug release. Methods to correlate biomarker release patterns to protease activity profiles in 3D breast cancer models will be explored. The PROTECT platform can then rapidly be repurposed for precision drug delivery. The PROVES concept will combine the excellent properties of liposomes for drug delivery and the optimal combination of proMAPs, based on the protease activity profile retrieved from the LABS, for optimized protease-triggered liposomal drug release. Combined, the LABS and PROVES concepts represent a unique and comprehensive platform for diagnostics and personalized cancer therapy. The proposed work goes far beyond stat-of-the-art and will address a significant and real bottleneck that hampers drug development and exploitation of proteases as diagnostics and prognostic cancer biomarkers.
Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-AG - HORIZON Action Grant Budget-BasedHost institution
581 83 Linkoping
Sweden