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Applicability, Safety And Biological Activity Of Regulatory T Cell Therapy In Liver Transplantation

Research output: Contribution to journalArticle

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Applicability, Safety And Biological Activity Of Regulatory T Cell Therapy In Liver Transplantation. / Sánchez-Fueyo, Alberto; Whitehouse, Gavin; Grageda, Nathali; Cramp, Matthew E; Lim, Tiong Y; Romano, Marco; Thirkell, Sarah; Lowe, Katie; Fry, Laura; Heward, Julie; Kerr, Alex; Ali, Jakia; Fisher, Chris; Lewis, Gillian; Hope, Andrew; Kodela, Elisavet; Lyne, Mike; Farzaneh, Farzin; Kordasti, Shahram; Rebollo-Mesa, Irene; Jose Lozano, Juan; Safinia, Niloufar; Lechler, Robert; Martínez-Llordella, Marc; Lombardi, Giovanna.

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 journalArticle

Harvard

Sánchez-Fueyo, A, Whitehouse, G, Grageda, N, Cramp, ME, Lim, TY, Romano, M, Thirkell, S, Lowe, K, Fry, L, Heward, J, Kerr, A, Ali, J, Fisher, C, Lewis, G, Hope, A, Kodela, E, Lyne, M, Farzaneh, F, Kordasti, S, Rebollo-Mesa, I, Jose Lozano, J, Safinia, N, Lechler, R, Martínez-Llordella, M & Lombardi, G 2019, 'Applicability, Safety And Biological Activity Of Regulatory T Cell Therapy In Liver Transplantation', American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. https://doi.org/10.1111/ajt.15700

APA

Sánchez-Fueyo, A., Whitehouse, G., Grageda, N., Cramp, M. E., Lim, T. Y., Romano, M., ... Lombardi, G. (2019). Applicability, Safety And Biological Activity Of Regulatory T Cell Therapy In Liver Transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. https://doi.org/10.1111/ajt.15700

Vancouver

Sánchez-Fueyo A, Whitehouse G, Grageda N, Cramp ME, Lim TY, Romano M et al. Applicability, Safety And Biological Activity Of Regulatory T Cell Therapy In Liver Transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2019 Nov 12. https://doi.org/10.1111/ajt.15700

Author

Sánchez-Fueyo, Alberto ; Whitehouse, Gavin ; Grageda, Nathali ; Cramp, Matthew E ; Lim, Tiong Y ; Romano, Marco ; Thirkell, Sarah ; Lowe, Katie ; Fry, Laura ; Heward, Julie ; Kerr, Alex ; Ali, Jakia ; Fisher, Chris ; Lewis, Gillian ; Hope, Andrew ; Kodela, Elisavet ; Lyne, Mike ; Farzaneh, Farzin ; Kordasti, Shahram ; Rebollo-Mesa, Irene ; Jose Lozano, Juan ; Safinia, Niloufar ; Lechler, Robert ; Martínez-Llordella, Marc ; Lombardi, Giovanna. / Applicability, Safety And Biological Activity Of Regulatory T Cell Therapy In Liver Transplantation. In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2019.

Bibtex Download

@article{dd60e6e0165d4e1b9f482cc8924f4e0b,
title = "Applicability, Safety And Biological Activity Of Regulatory T Cell Therapy In Liver Transplantation",
abstract = "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.",
author = "Alberto S{\'a}nchez-Fueyo and Gavin Whitehouse and Nathali Grageda and Cramp, {Matthew E} and Lim, {Tiong Y} and Marco Romano and Sarah Thirkell and Katie Lowe and Laura Fry and Julie Heward and Alex Kerr and Jakia Ali and Chris Fisher and Gillian Lewis and Andrew Hope and Elisavet Kodela and Mike Lyne and Farzin Farzaneh and Shahram Kordasti and Irene Rebollo-Mesa and {Jose Lozano}, Juan and Niloufar Safinia and Robert Lechler and Marc Mart{\'i}nez-Llordella and Giovanna Lombardi",
note = "{\circledC} 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.",
year = "2019",
month = "11",
day = "12",
doi = "10.1111/ajt.15700",
language = "English",
journal = "American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons",
issn = "1600-6135",
publisher = "Wiley-Blackwell",

}

RIS (suitable for import to EndNote) Download

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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