Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells. Academic Article uri icon


  • 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.

published proceedings

  • Nat Biotechnol

author list (cited authors)

  • Agarwalla, P., Ogunnaike, E. A., Ahn, S., Froehlich, K. A., Jansson, A., Ligler, F. S., Dotti, G., & Brudno, Y.

complete list of authors

  • Agarwalla, Pritha||Ogunnaike, Edikan A||Ahn, Sarah||Froehlich, Kristen A||Jansson, Anton||Ligler, Frances S||Dotti, Gianpietro||Brudno, Yevgeny

publication date

  • August 2022