Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells

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 may 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, following 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.