3D Centrifugation‐Enabled Priming of Synaptic Activation Promotes Primary T Cell Expansion

Abstract

Autologous cell therapy depends on T lymphocyte expansion efficiency and is hindered by suboptimal interactions between T cell receptors and peptide‐MHC molecules. Various artificial antigen presenting cell systems that enhance these interactions are often labor‐intensive, fabrication costly, highly variable, and potentially unscalable towards clinical setting. Here, 3D centrifugation‐enabled priming of T cell immune‐synapse junctions was performed to generate tight T cell–Dynabead aggregates at a rate 200‐fold faster than that of conventional 24‐h bulk shaking. Furthermore, by forming T cell–Dynabead aggregates in the starting culture, two‐ to six‐fold greater T cell expansion was achieved over conventional T cell expansion for cancer patient‐derived primary T cells while limiting over‐activation. Creating 3D T cell–Dynabead aggregates as the “booster” material enables highly efficient polyclonal T cell expansion without the need for complex surface modification of artificial antigen‐presenting cells. This method can be modularly adapted to existing T cell expansion processes for various applications, including adoptive cell therapies (ACTs).This article is protected by copyright. All rights reserved