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Clinical Grade Manufacturing of Human Alloantigen‐Reactive Regulatory T Cells for Use in Transplantation |
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| Authors: | A Medvec M Laszkowska M Wray M A Mintz E Trotta G L Szot W Liu A Lares K Lee A Laing R I Lechler J L Riley J A Bluestone G Lombardi Q Tang |
| Institution: | 1. Department of Microbiology, University of Pennsylvania, , Philadelphia, PA;2. Department of Surgery, University of California, , San Francisco, San Francisco, CA;3. UCSF Diabetes Center, University of California, , San Francisco, San Francisco, CA;4. MRC Centre for Transplantation, King's College London, , London, UK |
| 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. |
| Keywords: | Cellular therapy clinical application regulatory T cells tolerance induction |