Descripción del proyecto
Unos sueros antiofídicos seguros y asequibles están en el horizonte
Las mordeduras de serpientes venenosas afectan a 2,5 millones de personas y acaban con la vida de alrededor de 100 000 personas cada año. Los sueros antiofídicos convencionales a menudo provocan efectos secundarios graves y anafilaxia, y su producción resulta cara. El proyecto MABSTER, financiado con fondos europeos, desarrollará un método rentable para identificar y diseñar anticuerpos monoclonales humanos con propiedades especiales de enlace con toxinas que los haga sensibles a la regulación mediante el microentorno (como el pH). La investigación del proyecto aprovechará la selección de despliegue en fagos, la tecnología de micromatrices de péptidos de alta densidad y métodos de ingeniería de anticuerpos para descubrir y desarrollar anticuerpos monoclonales humanos que presenten una amplia reactividad cruzada, lo cual les permitirá neutralizar varias toxinas venenosas diferentes al mismo tiempo. Los buenos resultados del proyecto podrían generar nuevas formas de diseñar bioterapias para otras indicaciones complejas, como el cáncer, así como las enfermedades infecciosas y parasitarias.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
2800 Kongens Lyngby
Dinamarca