Enhanced Activation and Expansion of T Cells Using Mechanically Soft Elastomer Fibers

Emerging cellular therapies require effective platforms for producing clinically relevant numbers of high‐quality cells. This report introduces a materials‐based approach to improving expansion of T cells, a compelling agent for treatment of cancer and a range of other diseases. The system consists of electrospun fibers, which present activating antibodies to CD3 and CD28. These fibers are effective in activating T cells, initiating expansion, and simplify processing of the cellular product, compared to current bead‐base platforms. In addition, reducing the mechanical rigidity of these fibers enhances expansion of mixed populations of human CD4+ and CD8+ T cells, providing eightfold greater production of cells in each round of cell growth. This platform also rescues expansion of T cells isolated from CLL patients, which often show limited responsiveness and other features resembling exhaustion. By simplifying the process of cell expansion and improving T cell expansion, the system introduced here provides a powerful tool for the development of cellular immunotherapy. Cellular mechanosensing can be leveraged to improve systems for producing living cells. This report introduces a system of mechanically soft fibers of micro‐ and nanoscale dimension that enhances activation and expansion of T cells. By improving expansion of these cells, including those from patients undergoing treatment for cancer, this platform may provide a key capability for emerging immunotherapy strategies.