Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells
Menée in vitro et à l'aide de modèles murins, cette étude met en évidence l'intérêt d'un dispositif macroporeux implantable, comportant des cellules mononucléées du sang périphérique et des particules rétrovirales, pour fabriquer et libérer dans la circulation sanguine des lymphocytes CAR-T
Despite their clinical success, chimeric antigen receptor (CAR)-T cell therapies for B cell malignancies are limited by lengthy, costly and labor-intensive ex vivo manufacturing procedures that might lead to cell products with heterogeneous composition. Here we describe an implantable Multifunctional Alginate Scaffold for T Cell Engineering and Release (MASTER) that streamlines in vivo CAR-T cell manufacturing and reduces processing time to a single day. When seeded with human peripheral blood mononuclear cells and CD19-encoding retroviral particles, MASTER provides the appropriate interface for viral vector-mediated gene transfer and, after subcutaneous implantation, mediates the release of functional CAR-T cells in mice. We further demonstrate that in vivo-generated CAR-T cells enter the bloodstream and control distal tumor growth in a mouse xenograft model of lymphoma, showing greater persistence than conventional CAR-T cells. MASTER promises to transform CAR-T cell therapy by fast-tracking manufacture and potentially reducing the complexity and resources needed for provision of this type of therapy.
Nature Biotechnology 2022