Description du projet
Des sérums antivenimeux sûrs et abordables à l’horizon
Les morsures de serpents venimeux affectent 2,5 millions de personnes et en tuent environ 100 000 chaque année. Les antivenins conventionnels provoquent souvent des effets secondaires graves et une anaphylaxie chez les patients, en plus d’être coûteux à fabriquer. Le projet MABSTER, financé par l’UE, développera une approche rentable pour identifier et concevoir des anticorps monoclonaux humains dotés de propriétés de liaison aux toxines spéciales les rendant sensibles à la régulation par le microenvironnement (par exemple le pH). La recherche du projet exploitera la sélection de l’affichage des phages, la technologie des puces à ADN peptidiques à haute densité et les méthodes d’ingénierie des anticorps pour découvrir et développer des anticorps monoclonaux humains largement réactifs, leur permettant de neutraliser plusieurs toxines de venin différentes en même temps. Les résultats positifs du projet pourraient générer de nouvelles façons de concevoir des produits biothérapeutiques pour d’autres indications complexes, comme le cancer ou les maladies infectieuses et parasitaires.
Objectif
Snakebite envenoming is a Neglected Tropical Disease (NTD) that each year affects 2.5 million victims and kills >100,000, unless they are treated with antivenom. Conventional antivenoms, derived from immunized animals, inflict serum sickness and anaphylaxis in patients, and are costly to manufacture. Monoclonal human antibodies with special toxin-binding properties that are sensitive towards regulation by their microenvironment (e.g. pH), which may be discovered using phage display selection, may solve this issue, providing significant societal impact by enabling the development of cost-effective antivenoms to victims in low and middle-income countries. In this project, phage display selection, high-density peptide microarray technology, and antibody engineering techniques will in three scientific objectives be harnessed in the pursuit of developing novel methodologies for discovery of therapeutic human monoclonal antibodies that are recyclable (can neutralize more than one snake toxin per antibody), broadly cross-reactive (can neutralize different types of snake toxins), and that are both broadly cross-reactive and recyclable at the same time. This will open up for entirely new ways of designing biotherapeutics against complex indications, such snakebite envenoming, but also cancer, infectious, and parasitic diseases, where the targets can be elusive due to hyper-mutability. The ERC Starting Grant offers a unique opportunity to consolidate me as an international key scientific researcher in this field of antibody discovery and NTDs. I have already independently led a research group in this area for 2 years, I have in-depth experience with toxin-targeted antibody discovery (my dr.tech dissertation similar to the German “habilitation” will be submitted during fall 2018), and I am already involved in high level policy in the field of snakebite envenoming via my role as a scientific advisor for the World Health Organization.
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ERC-STG - Starting GrantInstitution d’accueil
2800 Kongens Lyngby
Danemark