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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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2017/8415205 |
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| author | Kannan P. Samy James R. Butler Ping Li David K. C. Cooper Burcin Ekser |
| author_facet | Kannan P. Samy James R. Butler Ping Li David K. C. Cooper Burcin Ekser |
| author_sort | Kannan P. Samy |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-0014832c2ca840c09b760d205d51384d |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-0014832c2ca840c09b760d205d51384d2025-08-20T02:01:46ZengWileyJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/84152058415205The Role of Costimulation Blockade in Solid Organ and Islet XenotransplantationKannan P. Samy0James R. Butler1Ping Li2David K. C. Cooper3Burcin Ekser4Division of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USADivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USADivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USAXenotransplantation Program, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USADivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USAPig-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.http://dx.doi.org/10.1155/2017/8415205 |
| spellingShingle | Kannan P. Samy James R. Butler Ping Li David K. C. Cooper Burcin Ekser The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation Journal of Immunology Research |
| 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 |
| url | http://dx.doi.org/10.1155/2017/8415205 |
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