Enhanced activation and expansion of T cells using mechanically soft elastomer fibers.

摘要

Practical deployment of cellular therapies requires effective platforms for producing clinically relevant numbers of high-quality cells. This report introduces a materials-based approach to improving activation and expansion of T cells, which are rapidly emerging as an agent for treating cancer and a range of other diseases. Electrospinning is used to create a mesh of poly(ε-caprolactone) fibers, which is used to present activating ligands to CD3 and CD28, which activate T cells for expansion. Incorporation of poly(dimethyl siloxane) elastomer into the fibers reduces substrate rigidity and enhances expansion of mixed populations of human CD4⁺ and CD8⁺ T cells. Intriguingly, 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, compared to current bead-based platforms, and improving T cell expansion, the system introduced here may accelerate development of cellular immunotherapy.