Project description DEENESFRITPL What if we could kill diseased cells without harming normal tissues? Scientists have been searching for a ‘magic bullet’ to selectively target disease causing cells for decades, but current treatments for cancer and chronic inflammatory diseases fall short of this ideal. Monoclonal antibodies, while providing specific targeting, are often not curative as single agents, and attempts to ‘arm’ them with drugs or cytokines have resulted in unacceptable toxicities. In this context, the ground-breaking European Research Council-funded ZAUBERKUGEL project proposes a solution that could change the game entirely. This involves the controlled release of cytotoxic drugs or stepwise non-covalent assembly of cytokines. Innovative proteomic methodologies, based on human leucocyte antigen-peptidome analysis, will be used to profile response to therapy. This approach holds considerable potential for treating serious diseases with ‘activity on demand’ pharmaceutical agents. Show the project objective Hide the project objective Objective "Paul Ehrlich was the first scientist to postulate that if a compound could be made that selectively targeted disease-causing cells, then this agent could be used for the delivery of a toxin, which would enable a pharmacotherapy of unprecedented potency and selectivity. With this procedure, a ""magic bullet"" (Zauberkugel, his term for an ideal therapeutic agent) would be created, that killed diseased cells while sparing normal tissues.The concept of a ""magic bullet"" was to some extent realized by the invention of monoclonal antibodies, as these molecules provide a very specific binding affinity to their cognate target. However, monoclonal antibodies used as single agents are typically not able to induce cures for cancer or chronic inflammatory diseases. More recently, intense academic and industrial research activities have aimed at “arming” monoclonal antibodies with drugs or cytokines, in order to preferentially deliver these therapeutic payloads to the site of disease. Unfortunately, in most cases, ""armed"" antibody products still cause unacceptable toxicities, which prevent escalation to potentially curative dose regimens.In this Project, I outline a therapeutic strategy, which relies on the use of extremely specific tumor targeting agents, for the selective delivery of payloads, which can be conditionally activated at the site of disease. Methodologies for the conditional generation of active payloads include the stepwise non-covalent assembly of cytokines and the controlled release of cytotoxic drugs at suitable time points after injection, when the concentration of therapeutic agent in normal organs is acceptably low. Response to therapy will be profiled using innovative proteomic methodologies, based on HLA-peptidome analysis.Pharmaceutical agents with “activity on demand” hold a considerable potential not only for the therapy of cancer, but also for the treatment of other serious diseases, including certain highly debilitating chronic inflammatory condition" Fields of science medical and health scienceshealth sciencesinflammatory diseasesmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsmedical and health sciencesclinical medicineoncologylung cancermedical and health sciencesclinical medicineoncologyskin cancermelanomamedical and health sciencesbasic medicineimmunology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-ADG-2014 - ERC Advanced Grant Call for proposal ERC-2014-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Net EU contribution € 2 000 000,00 Address Raemistrasse 101 8092 Zuerich Switzerland See on map Region Schweiz/Suisse/Svizzera Zürich Zürich Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 000 000,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Switzerland Net EU contribution € 2 000 000,00 Address Raemistrasse 101 8092 Zuerich See on map Region Schweiz/Suisse/Svizzera Zürich Zürich Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 000 000,00
