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The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation

Pig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advanc...

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Autores principales: Samy, Kannan P., Butler, James R., Li, Ping, Cooper, David K. C., Ekser, Burcin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660816/
https://www.ncbi.nlm.nih.gov/pubmed/29159187
http://dx.doi.org/10.1155/2017/8415205
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author Samy, Kannan P.
Butler, James R.
Li, Ping
Cooper, David K. C.
Ekser, Burcin
author_facet Samy, Kannan P.
Butler, James R.
Li, Ping
Cooper, David K. C.
Ekser, Burcin
author_sort Samy, Kannan P.
collection PubMed
description Pig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials. However, as these humoral immune barriers to cross-species transplantation are overcome with advanced transgenics, cellular immunity to these novel xenografts remains an outstanding issue. Therefore, understanding and optimizing immunomodulation will be paramount for successful clinical xenotransplantation. Costimulation blockade agents have been introduced in xenotransplantation research in 2000 with anti-CD154mAb. Most recently, prolonged survival has been achieved in solid organ (kidney xenograft survival > 400 days with anti-CD154mAb, heart xenograft survival > 900 days, and liver xenograft survival 29 days with anti-CD40mAb) and islet xenotransplantation (>600 days with anti-CD154mAb) with the use of these potent experimental agents. As the development of novel genetic modifications and costimulation blocking agents converges, we review their impact thus far on preclinical xenotransplantation and the potential for future application.
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spelling pubmed-56608162017-11-20 The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation Samy, Kannan P. Butler, James R. Li, Ping Cooper, David K. C. Ekser, Burcin J Immunol Res Review Article Pig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials. However, as these humoral immune barriers to cross-species transplantation are overcome with advanced transgenics, cellular immunity to these novel xenografts remains an outstanding issue. Therefore, understanding and optimizing immunomodulation will be paramount for successful clinical xenotransplantation. Costimulation blockade agents have been introduced in xenotransplantation research in 2000 with anti-CD154mAb. Most recently, prolonged survival has been achieved in solid organ (kidney xenograft survival > 400 days with anti-CD154mAb, heart xenograft survival > 900 days, and liver xenograft survival 29 days with anti-CD40mAb) and islet xenotransplantation (>600 days with anti-CD154mAb) with the use of these potent experimental agents. As the development of novel genetic modifications and costimulation blocking agents converges, we review their impact thus far on preclinical xenotransplantation and the potential for future application. Hindawi 2017 2017-10-11 /pmc/articles/PMC5660816/ /pubmed/29159187 http://dx.doi.org/10.1155/2017/8415205 Text en Copyright © 2017 Kannan P. Samy et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Samy, Kannan P.
Butler, James R.
Li, Ping
Cooper, David K. C.
Ekser, Burcin
The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation
title The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation
title_full The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation
title_fullStr The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation
title_full_unstemmed The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation
title_short The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation
title_sort role of costimulation blockade in solid organ and islet xenotransplantation
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660816/
https://www.ncbi.nlm.nih.gov/pubmed/29159187
http://dx.doi.org/10.1155/2017/8415205
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