In Vivo CAR-T Generation Using scFv-Decorated Lipid Nanoparticles Targeting T-Lymphocytes for mRNA Delivery

Laura Molero Solis – R+D Scientist / PhD candidate, Pharmaceutical development, Reig Jofre; Jessica Malavia Muñoz – Analytical development technician, CDMO, Reig Jofre; Ferran Roig Roig – Galenical development technician, CDMO, Reig jofre; Manpreet Kaur – R+D Scientist, LEITAT; Julieta Carabelli – Principal Research Scientist, Health & Biomedicine Department, LEITAT; Laura Padilla – Principal Research Scientist, Health & Biomedicine Department, LEITAT; Anna Lagunas – Research Leader, Nanobioengineering, IBEC; Elisabet Rosell Vives – Science Liason, Reig Jofre; Josep Samitier – Director, Nanobioengineering, IBEC; Laia Montell Bonaventura – Science Liason, Science, Reig Jofre

Introduction: Multidrug-resistant bacteria cause severe hospital infections and represent a major global health threat. CAR-T therapy is a powerful immunotherapeutic strategy, but its clinical use relies on complex and expensive ex vivo T-cell manipulation. An alternative approach is the in vivo generation of CAR-T cells using lipid nanoparticles (LNPs) that deliver CAR-encoding mRNA. By surface-functionalizing LNPs with ligands or antibody fragments that recognize T-cell markers, selective targeting can be achieved. This work evaluates chemical strategies to decorate LNPs with targeting moieties as a step toward in vivo CAR-T therapies against multidrug-resistant pathogens.