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Clinically Available Immunosuppressive Agents Prolong Pig-to-Primate Kidney Xenograft Survival

I. J. Anwar1, Q. Gao1, I. DeLaura1, J. Yoon1, R. Baldi1, M. Youd2, K. Stiede2, K. Hall2, S. Knechtle1, J. Kwun1

1Surgery, Duke Transplant Center, Durham, NC, 2eGenesis Inc, Cambridge, MA

Meeting: 2022 American Transplant Congress

Abstract number: 1532

Keywords: Antilymphocyte antibodies, Co-stimulation, Immunosuppression, Kidney transplantation

Topic: Basic Science » Basic Science » 13 - Xenotransplantation

Session Information

Session Name: Xenotransplantation

Session Type: Poster Abstract

Date: Tuesday, June 7, 2022

Session Time: 7:00pm-8:00pm

 Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: Most immunosuppressive regimens used in Pig-To-Primate Xenotransplantation contain anti-CD154 agents, compounds that are currently not FDA-approved. The aim of this study was to assess whether a regimen made up of clinically available immunosuppressive agents prolonged xenograft survival.

*Methods: Cynomolgus macaques received life-sustaining kidney transplants from triple-knockout pigs with 7 additional human genes (provided by eGenesis; n=6). Animals received Thymoglobulin® as induction therapy and maintenance regimen consisted of either Belatacept/Rapamycin/MMF/Steroids (n=2) or anti-human CD154 mAb (5C8H1 clone)/MMF/Steroids (n=2). Two animals were excluded from post-transplant analysis due to technical complications.

*Results: All animals tolerated xeno-kidney transplantation well with no cases of hyperacute rejection. Animals treated with Belatacept/Rapamycin showed a trend towards prolonged graft survival compared to animals treated with anti-CD154 mAb (median survival time 35d vs. 24d, Figure 1A). One animal in the Belatacept/Rapamycin group developed class II pig-donor specific antibodies, while both animals in the anti-CD154 mAb developed both class I and class II pig-donor specific antibodies (Figure 1B).

*Conclusions: A regimen consisting of Thymoglobulin® /Belatacept/Rapamycin prolonged xenograft survival while preventing class I pig-donor specific antibodies formation. Surprisingly, both animals treated with anti-CD154 mAb developed class I and II pig-donor specific antibodies. Further studies are warranted to further characterize the efficacy of this clinically available regimen in xenotransplantation.

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To cite this abstract in AMA style:

Anwar IJ, Gao Q, DeLaura I, Yoon J, Baldi R, Youd M, Stiede K, Hall K, Knechtle S, Kwun J. Clinically Available Immunosuppressive Agents Prolong Pig-to-Primate Kidney Xenograft Survival [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/clinically-available-immunosuppressive-agents-prolong-pig-to-primate-kidney-xenograft-survival/. Accessed May 29, 2025.

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