Open AccessBioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells
Author(s) -
Pritha Agarwalla,
Edikan A. Ogunnaike,
Sarah Ahn,
Kristen Froehlich,
Anton Jansson,
Frances S. Ligler,
Gianpietro Dotti,
Yevgeny Brudno
Publication year - 2022
Publication title -
nature biotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.358
H-Index - 445
eISSN - 1546-1696
pISSN - 1087-0156
DOI - 10.1038/s41587-022-01245-x
Subject(s) - chimeric antigen receptor , in vivo , cd19 , ex vivo , cell therapy , peripheral blood mononuclear cell , viral vector , cell , t cell , immunology , microbiology and biotechnology , cancer research , in vitro , antigen , biology , stem cell , gene , immune system , genetics , recombinant dna
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.