Microfluidic T cell selection by cellular avidity.
Author(s)
Type
Journal Article
Abstract
No T cell receptor (TCR) T cell therapies have obtained clinical approval. The lack of strategies capable of selecting and recovering potent T cell candidates may be a contributor to this. Existing protocols for selecting TCR T cell clones for cell therapies such as peptide-MHC multimer methods have provided effective measurements on TCR affinities. However, these methods lack the ability to measure the collective strength of intercellular interactions (i.e., cellular avidity) and markers of T cell activation such as immunological synapse formation. This study describes a novel microfluidic fluid shear stress-based approach to identify and recover highly potent T cell clones based on the cellular avidity between living T cells and tumor cells. Our approach is capable of probing approximately up to 10,000 T cell-tumor cell interactions per run and can discriminate and recover highly potent T cells with up to 100% purity from mixed populations of T cells within 30 minutes. Markers of cytotoxicity, activation and binding avidity persisted when recovered high cellular avidity T cells were subsequently exposed to fresh tumor cells. These results demonstrate how microfluidic probing of cellular avidity may fast track the therapeutic T cell selection process and move us closer to precision cancer immunotherapy. This article is protected by copyright. All rights reserved.
Date Issued
2022-08-17
Date Acceptance
2022-06-03
Citation
Advanced Healthcare Materials, 2022, 11 (16), pp.1-14
ISSN
2192-2640
Publisher
Wiley-VCH Verlag
Start Page
1
End Page
14
Journal / Book Title
Advanced Healthcare Materials
Volume
11
Issue
16
Copyright Statement
© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35657072
Subjects
T cell receptor
avidity
cytotoxicity
immunotherapy
microfluidics
shear stress
synapse
Publication Status
Published
Coverage Spatial
Germany
Date Publish Online
2022-06-21