Clinical Grade Manufacturing of Human Alloantigen‐Reactive Regulatory T Cells for Use in Transplantation. Issue 11 (18th September 2013) - Putnam, A. L.
Abstract: Regulatory T cell (Treg) therapy has the potential to induce transplantation tolerance so that immunosuppression and associated morbidity can be minimized. Alloantigen‐reactive Tregs (arTregs) are more effective at preventing graft rejection than polyclonally expanded Tregs (PolyTregs) in murine models. We have developed a manufacturing process to expand human arTregs in short‐term cultures using good manufacturing practice‐compliant reagents. This process uses CD40L‐activated allogeneic B cells to selectively expand arTregs followed by polyclonal restimulation to increase yield. Tregs expanded 100‐ to 1600‐fold were highly alloantigen reactive and expressed the phenotype of stable Tregs. The alloantigen‐expanded Tregs had a diverse TCR repertoire. They were more potent than PolyTregs in vitro and more effective at controlling allograft injuries in vivo in a humanized mouse model. Abstract : This study details a good manufacturing practice‐compliant process for short‐term selective expansion of donoralloantigen‐reactive regulatory T cells for therapeutic applications in transplantation.