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ZUTPHEN, Netherlands

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Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.2-1 | Award Amount: 8.32M | Year: 2012

Chemotherapy is slowly being supplemented by a new generation of drugs that recognize specific targets in or on cancer cells and has proven to be more effective with markedly fewer side effects. During the course of the disease alternative oncogenic signaling pathways take over inevitably leading to drug resistance. As a consequence renewed tumor analysis is required to redefine the optimal treatment regiment. However a biopsy can frequently not be obtained without risk and or discomfort to the patient. Circulating tumor cells (CTC) may circumvent this problem. CTC refer to cells that detach from a primary tumor or metastatic site, circulate in the peripheral blood and may form metastasis. CTC represent a liquid biopsy that can be used to tailor treatment for individual patients. CTC are however rare and can only be obtained for further characterization in a small fraction of patients. In the CTCtrap consortium universities, research institutions and SMEs are linked in a common effort, starting from the simple, but innovative view of using Therapeutic Apheresis (TA), as a way to collect CTC from peripheral blood in cancer patients. A new TA column will be developed to capture CTC and then reintroduce the blood devoid of tumor cells back into the body with the promise to obtain CTC in all patients at risk for recurrence or diagnosed with metastatic disease. The molecular characterization of these CTC is expected to gather new knowledge on metastasis mechanism, provide a risk assessment and the optimal therapy choice during the course of the disease of cancer patients. The new knowledge on CTC heterogeneity within cancer type and within individuals will allow for the tuning of CTCapheresis to specific cancer types. Prospective pilot studies will be setup to investigate the feasibility of the CTCapheresis in the clinic and their potential therapeutic benefit. Success of CTCapheresis will lead to a radical change in the diagnosis and treatment of solid tumors.


There is strong interest in the development of novel functionalized membranes which can be used as microsieves, as a component of integrated analytical systems, in food processing, drug discovery and diagnostic applications. This project is based on a combination of three break-through technologies, developed by the applicants in the past, with high impact for nano(bio)technological application: (i) the S-layer technology allowing the construction of nanoporous protein lattices, (ii) the biocatalytic formation of inorganic materials by silicatein, a group of unique enzymes capable to catalyze the formation of porous silica from soluble precursors, and (iii) the sol-gel technique for encapsulation (immobilization) of biomolecules serving as biocatalyst or as a component of sensors. The goal of this project is to design and fabricate - based on molecular biology inspired approaches - nano-porous bio-inorganic membranes with novel functionalities for industrial application. These membranes will be formed by S-layer proteins, which are able to assemble to highly ordered structures of defined pore-size, and recombinant silicateins or silicatein fusion proteins. The hydrated silica glass layer formed by silicatein will be used to encase biocatalysts (enzymes) or antibodies against small molecules as sample prep- or sensor components of integrated systems. The innovative type of the functionalized membranes developed in this project thus exploits two principles: (i) protein self-assembly and - and this has not been done before - (ii) enzymatic (silicatein-mediated) deposition of inorganic material used for reinforcement of the membranes as well as for encasing biomolecules, providing the membranes with new functionalities. The new technique will be exploited by three research-based SMEs and the enduser involved in the project, in microfluidics based sample processing and micro-array development, in industrial nanosieves, as well as in sensors in drinking water systems.

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