Soft Synthetic Cells with Mobile Membrane Ligands for Ex Vivo Expansion of Therapy-Relevant T Cell Phenotypes.

Autor: Burgstaller A; INM - Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany.; Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Center for Infection Research, Campus E8 1, 66123, Saarbrücken, Germany.; Center for Biophysics, Saarland University, Campus Saarland, 66123, Saarbrücken, Germany., Piernitzki N; INM - Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany.; Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Center for Infection Research, Campus E8 1, 66123, Saarbrücken, Germany.; Center for Biophysics, Saarland University, Campus Saarland, 66123, Saarbrücken, Germany., Küchler N; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Building 48, 66421, Homburg, Germany., Koch M; INM - Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany., Kister T; INM - Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany., Eichler H; Institute of Clinical Hemostaseology and Transfusion Medicine, Saarland University and Saarland University Medical Center, Homburg, Germany., Kraus T; INM - Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany.; Saarland University, Colloid and Interface Chemistry, 66123, Saarbrücken, Germany., Schwarz EC; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Building 48, 66421, Homburg, Germany., Dustin ML; Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal Sciences, University of Oxford, Oxford, UK., Lautenschläger F; Center for Biophysics, Saarland University, Campus Saarland, 66123, Saarbrücken, Germany.; Experimental Physics, Faculty of Natural Science and Technology, Saarland University, Campus Saarbrücken, 66123, Saarbrücken, Germany., Staufer O; INM - Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany.; Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Center for Infection Research, Campus E8 1, 66123, Saarbrücken, Germany.; Center for Biophysics, Saarland University, Campus Saarland, 66123, Saarbrücken, Germany.; Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal Sciences, University of Oxford, Oxford, UK.; Max Planck Bristol Centre for Minimal Biology, Cantock's Close, Bristol, BS8 1TS, UK.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Sep; Vol. 20 (37), pp. e2401844. Date of Electronic Publication: 2024 May 15.
DOI: 10.1002/smll.202401844
Abstrakt: The expansion of T cells ex vivo is crucial for effective immunotherapy but currently limited by a lack of expansion approaches that closely mimic in vivo T cell activation. Taking inspiration from bottom-up synthetic biology, a new synthetic cell technology is introduced based on dispersed liquid-liquid phase-separated droplet-supported lipid bilayers (dsLBs) with tunable biochemical and biophysical characteristics, as artificial antigen presenting cells (aAPCs) for ex vivo T cell expansion. These findings obtained with the dsLB technology reveal three key insights: first, introducing laterally mobile stimulatory ligands on soft aAPCs promotes expansion of IL-4/IL-10 secreting regulatory CD8 + T cells, with a PD-1 negative phenotype, less prone to immune suppression. Second, it is demonstrated that lateral ligand mobility can mask differential T cell activation observed on substrates of varying stiffness. Third, dsLBs are applied to reveal a mechanosensitive component in bispecific Her2/CD3 T cell engager-mediated T cell activation. Based on these three insights, lateral ligand mobility, alongside receptor- and mechanosignaling, is proposed to be considered as a third crucial dimension for the design of ex vivo T cell expansion technologies.
(© 2024 The Authors. Small published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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