Clinical Grade Manufacturing of Human Alloantigen-Reactive Regulatory T Cells for Use in Transplantation

作者：Amy L. Putnam, Niloufar Safinia, Andrew R. Medvec, Monika Laszkowska, M. Wray, Michelle A. Mintz, Eleonora Trotta, Gregory L. Szot, W Liu, Angela Lares, K. Lee, Adam G. Laing, Robert Ian Lechler, James L. Riley, Jeffrey A. Bluestone, Giulia Lombardi, Qizhi Tang · 发表于：American Journal of Transplantation · 年份：2013 · DOI：10.1111/ajt.12433 · 被引用次数：260 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Hematopoietic Stem Cell Transplantation

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.