Project description
Artificial cells with anti-tumour T cell function
T cells are vital in anti-cancer defence, yet tumour evasion strategies limit their effectiveness. Decades of research have focused on developing T cell therapies from donor cells to treat chemoresistant cancers. However, various factors, such as economic considerations and life-threatening side effects, still hinder the potential of donor-derived T cells engineered against tumours. Funded by the European Innovation Council, the ArTCell project aims to overcome these limitations by developing artificial T cells that mimic the tumour-recognition and killing properties of T cells. Researchers will incorporate cytotoxic and tumour-recognising components of activated T cells into lipid-based vesicles to provide a safer, more efficient and cost-effective alternative, bypassing limitations hindering the wider use of current cell-based therapies.
Objective
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
Fields of science
Programme(s)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Funding Scheme
HORIZON-EIC - HORIZON EIC GrantsCoordinator
3000 Leuven
Belgium