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Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation.

  • Author(s): Putnam, AL
  • Safinia, N
  • Medvec, A
  • Laszkowska, M
  • Wray, M
  • Mintz, MA
  • Trotta, E
  • Szot, GL
  • Liu, W
  • Lares, A
  • Lee, K
  • Laing, A
  • Lechler, RI
  • Riley, JL
  • Bluestone, JA
  • Lombardi, G
  • Tang, Q
  • et al.

Published Web Location

https://doi.org/10.1111/ajt.12433
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.

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