Description du projet
Des cellules artificielles dotées d’une fonction de lymphocyte T anti-tumorale
Les lymphocytes T sont essentiels aux défenses anticancéreuses, mais les stratégies d’évasion des tumeurs limitent toutefois leur efficacité. Des décennies de recherche ont été consacrées au développement de thérapies par lymphocytes T à partir de cellules de donneurs pour le traitement des cancers chimiorésistants. Divers facteurs, tels que des considérations économiques et les effets secondaires potentiellement mortels, entravent toutefois le potentiel des lymphocytes T dérivés de donneurs et conçus pour lutter contre les tumeurs. Financé par le Conseil européen de l’innovation, le projet ArTCell entend surmonter ces limitations en développant des lymphocytes T artificiels qui imitent les propriétés de reconnaissance et d’élimination des tumeurs des lymphocytes T. Les chercheurs incorporeront les composants cytotoxiques et de reconnaissance des tumeurs des lymphocytes T activés dans des vésicules à base de lipides afin de fournir une alternative plus sûre, plus efficace et plus rentable, contournant les limitations qui entravent une utilisation plus large des thérapies cellulaires actuelles.
Objectif
T cells play a central role in anti-tumor immune protection. While their ability to target and eliminate emerging tumor cells is increasingly recognized, fully-established tumors can efficiently evade T cell response. Significant efforts spanning several decades of research have been made to develop T cell-based therapies manufactured from donor-derived T cells. The use of tumor-directed T cells engineered to express chimeric antigen receptors (CARs) represents, to date, one of the most successful applications for treatment of chemoresistant cancers. However, several major drawbacks, including economic factors, suboptimal functioning and life-threatening side effects, are still hindering the full potential of T cell-based therapies. To address this issue, we aim to generate Artificial T cells (ArTCell) that will mimic the anti-tumor function of a T cell-based therapy but in a safer, more efficient and less expensive product. ArTCells will incorporate two key features of activated T cells into Giant Unilamellar Vesicles (GUVs): the specificity of tumor cell recognition and the cytotoxic activity achieved through death ligands and cytolytic proteins. Functionalization of the GUVs will be confirmed by immunofluorescent labelling of membrane proteins (i.e. TRAIL, LFA-1 and CAR) and detection with flow cytometry. The morphology of ArTCell will be monitored via cryo-EM, SEM, and confocal microscopy. The ability of ArTCell to target and kill tumour cells will be thoroughly validated in vitro by a combination of functional and high resolution live imaging assays as well as in vivo with two cell line- and patient-xenografts mouse models. The ArTCell could allow to circumvent many of the current technological limitations that hinder a more wide-spread applicability of cell-based therapies, without being subject to tumor-mediated inactivation
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Régime de financement
HORIZON-EIC - HORIZON EIC GrantsCoordinateur
3000 Leuven
Belgique