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

Journal article

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.

Authors: Burgstaller, A; Piernitzki, N; Küchler, N; Koch, M; Kister, T

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Small
• Article number: 2401844
• Publication date: 2024-05-15
• DOI: 10.1002/smll.202401844
• EISSN: 1613-6829
• ISSN: 1613-6829 and 1613-6810
• Language: English
• Keywords: bottom‐up synthetic biology; CD8 Treg; synthetic cells; cell mimics; elastomers; immunotherapy; supported lipid bilayers; synthetic immunology