Descripción del proyecto
Células artificiales con función de linfocitos T antitumorales
Los linfocitos T tienen una gran importancia en la lucha contra el cáncer, pero las estrategias de evasión tumoral limitan su eficacia. Durante decenios, las investigaciones se han centrado en el desarrollo de terapias con linfocitos T a partir de células de donantes para tratar tumores quimiorresistentes. Sin embargo, diversos factores, como las consideraciones económicas o los efectos secundarios potencialmente mortales, siguen obstaculizando el potencial de los linfocitos T modificados derivados de donantes para combatir tumores. En el proyecto ArTCell, financiado por el Consejo Europeo de Innovación, se pretende superar estas limitaciones desarrollando linfocitos T artificiales que imiten las propiedades de reconocimiento y destrucción de tumores de los linfocitos T. Sus investigadores incorporarán componentes citotóxicos y de reconocimiento tumoral de los linfocitos T activados a vesículas lipídicas para, de este modo, ofrecer una alternativa más segura, eficaz y rentable, así como circunvenir las limitaciones al uso generalizado de las terapias celulares actuales.
Objetivo
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
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Convocatoria de propuestas
HORIZON-EIC-2023-PATHFINDEROPEN-01
Consulte otros proyectos de esta convocatoriaRégimen de financiación
HORIZON-EIC - HORIZON EIC GrantsCoordinador
3000 Leuven
Bélgica