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Journal of Immunology Research
Volume 2017, Article ID 8415205, 11 pages
https://doi.org/10.1155/2017/8415205
Review Article

The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation

1Division of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
2Xenotransplantation Program, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence should be addressed to Burcin Ekser; ude.iupui@reskeb

Received 17 July 2017; Accepted 17 September 2017; Published 11 October 2017

Academic Editor: Vered Padler-Karavani

Copyright © 2017 Kannan P. Samy et al. 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.

Abstract

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.