Research output: Contribution to journal › Article › peer-review
Applicability, Safety And Biological Activity Of Regulatory T Cell Therapy In Liver Transplantation. / Sánchez-Fueyo, Alberto; Whitehouse, Gavin; Grageda, Nathali et al.
In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 12.11.2019.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Applicability, Safety And Biological Activity Of Regulatory T Cell Therapy In Liver Transplantation
AU - Sánchez-Fueyo, Alberto
AU - Whitehouse, Gavin
AU - Grageda, Nathali
AU - Cramp, Matthew E
AU - Lim, Tiong Y
AU - Romano, Marco
AU - Thirkell, Sarah
AU - Lowe, Katie
AU - Fry, Laura
AU - Heward, Julie
AU - Kerr, Alex
AU - Ali, Jakia
AU - Fisher, Chris
AU - Lewis, Gillian
AU - Hope, Andrew
AU - Kodela, Elisavet
AU - Lyne, Mike
AU - Farzaneh, Farzin
AU - Kordasti, Shahram
AU - Rebollo-Mesa, Irene
AU - Jose Lozano, Juan
AU - Safinia, Niloufar
AU - Lechler, Robert
AU - Martínez-Llordella, Marc
AU - Lombardi, Giovanna
N1 - © 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.
PY - 2019/11/12
Y1 - 2019/11/12
N2 - Regulatory T cells (Tregs) are a lymphocyte subset with intrinsic immunosuppressive properties that can be expanded in large numbers ex vivo and have been shown to prevent allograft rejection and promote tolerance in animal models. To investigate the safety, applicability and biological activity of autologous Treg adoptive transfer in humans, we conducted an open-label, dose escalation, Phase I clinical trial in liver transplantation. Patients were enrolled while awaiting liver transplantation or 6-12 months post-transplant. Circulating Tregs were isolated from blood or leukapheresis, expanded under GMP conditions, and administered i.v at either 0.5-1 million Tregs/kg or 3-4.5 million Tregs/kg. The primary endpoint was the rate of dose limiting toxicities occurring within 4 weeks of infusion. The applicability of the clinical protocol was poor unless patient recruitment was deferred until 6-12 months post-transplantation. Thus, only 3 out of the 17 patients consented while awaiting liver transplantation were dosed. In contrast, all 6 patients consented 6-12 months post-transplantation received the cell infusion. Treg transfer was safe and transiently increased the pool of circulating Tregs and reduced anti-donor T cell responses. Our study opens the door to employing Treg immunotherapy to facilitate the reduction or complete discontinuation of immunosuppression following liver transplantation.
AB - Regulatory T cells (Tregs) are a lymphocyte subset with intrinsic immunosuppressive properties that can be expanded in large numbers ex vivo and have been shown to prevent allograft rejection and promote tolerance in animal models. To investigate the safety, applicability and biological activity of autologous Treg adoptive transfer in humans, we conducted an open-label, dose escalation, Phase I clinical trial in liver transplantation. Patients were enrolled while awaiting liver transplantation or 6-12 months post-transplant. Circulating Tregs were isolated from blood or leukapheresis, expanded under GMP conditions, and administered i.v at either 0.5-1 million Tregs/kg or 3-4.5 million Tregs/kg. The primary endpoint was the rate of dose limiting toxicities occurring within 4 weeks of infusion. The applicability of the clinical protocol was poor unless patient recruitment was deferred until 6-12 months post-transplantation. Thus, only 3 out of the 17 patients consented while awaiting liver transplantation were dosed. In contrast, all 6 patients consented 6-12 months post-transplantation received the cell infusion. Treg transfer was safe and transiently increased the pool of circulating Tregs and reduced anti-donor T cell responses. Our study opens the door to employing Treg immunotherapy to facilitate the reduction or complete discontinuation of immunosuppression following liver transplantation.
U2 - 10.1111/ajt.15700
DO - 10.1111/ajt.15700
M3 - Article
C2 - 31715056
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
SN - 1600-6135
ER -
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