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

Autor: Agarwalla P; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA.; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA., Ogunnaike EA; Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Ahn S; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Froehlich KA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA.; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA., Jansson A; Analytical Instrumentation Facility, North Carolina State University, Raleigh, NC, USA., Ligler FS; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA.; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA., Dotti G; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Brudno Y; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. ybrudno@ncsu.edu.; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA. ybrudno@ncsu.edu.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. ybrudno@ncsu.edu.
Jazyk: angličtina
Zdroj: Nature biotechnology [Nat Biotechnol] 2022 Aug; Vol. 40 (8), pp. 1250-1258. Date of Electronic Publication: 2022 Mar 24.
DOI: 10.1038/s41587-022-01245-x
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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