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

TY - JOUR

T1 - Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation

AU - Putnam, A L

AU - Safinia, N

AU - Medvec, A

AU - Laszkowska, M

AU - Wray, M

AU - Mintz, M A

AU - Trotta, E

AU - Szot, G L

AU - Liu, W

AU - Lares, A

AU - Lee, K

AU - Laing, A

AU - Lechler, R I

AU - Riley, J L

AU - Bluestone, J A

AU - Lombardi, G

AU - Tang, Q

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

U2 - 10.1111/ajt.12433

DO - 10.1111/ajt.12433

M3 - Article

C2 - 24102808

SN - 1600-6135

VL - 13

SP - 3010

EP - 3020

JO - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

IS - 11

ER -