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

Author:

Burgstaller Anna123,Piernitzki Nils123,Küchler Nadja4,Koch Marcus1,Kister Thomas1,Eichler Hermann5,Kraus Tobias16,Schwarz Eva C.4,Dustin Michael L.7,Lautenschläger Franziska38,Staufer Oskar12379ORCID

Affiliation:

1. INM – Leibniz Institute for New Materials Campus D2 2 66123 Saarbrücken Germany

2. Helmholtz Institute for Pharmaceutical Research Saarland Helmholtz Center for Infection Research Campus E8 1 66123 Saarbrücken Germany

3. Center for Biophysics Saarland University Campus Saarland 66123 Saarbrücken Germany

4. Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM) School of Medicine, Saarland University Building 48 66421 Homburg Germany

5. Institute of Clinical Hemostaseology and Transfusion Medicine Saarland University and Saarland University Medical Center Homburg Germany

6. Saarland University, Colloid and Interface Chemistry 66123 Saarbrücken Germany

7. Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal Sciences University of Oxford Oxford UK

8. Experimental Physics, Faculty of Natural Science and Technology Saarland University Campus Saarbrücken 66123 Saarbrücken Germany

9. Max Planck Bristol Centre for Minimal Biology Cantock's Close Bristol BS8 1TS UK

Abstract

AbstractThe 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.

Funder

Deutsche Forschungsgemeinschaft

Joachim Herz Stiftung

Daimler und Benz Stiftung

Publisher

Wiley

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