Induction of Delayed Renal Allograft Tolerance Using Only Clinically Available Reagents in Non-Human Primates.
Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA
Meeting: 2017 American Transplant Congress
Abstract number: 206
Keywords: Graft survival, Kidney transplantation, Primates, Tolerance
Session Information
Session Name: Concurrent Session: Basic Transplant Tolerance I
Session Type: Concurrent Session
Date: Monday, May 1, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 2:42pm-2:54pm
Location: E350
Background: We have previously reported successful induction of renal allograft tolerance following a period of conventional immunosuppression (Delayed tolerance) using nonmyeloablative conditioning that included anti-CD154 and anti-CD8 mAbs or LFA3-Ig in MHC-mismatched kidney transplantation (KTx). Since these reagents are not currently clinically available, the protocol must be revised to be applicable to deceased donor allografts. In this study, we evaluated clinically available reagents, CTLA4Ig(belatacept) and rabbit-ATG (Thymoglobulin), for induction of delayed tolerance.
Methods: KTx was performed with triple drug immunosuppression (I.S.) (tacrolimus, mycophenolate mofetil and predonisone) in MHC mismatched cynomolgus monkeys. Four months after KTx, recipients received donor bone marrow transplant (BMT) after a nonmyeloablative conditioning regimen including low dose TBI, thymic irradiation, belatacept, Thymoglobulin and a one month course of CyA.
Results: The first monkey received the regimen with Thymoglobulin (20mg/kg[times]3) and belatacept (20mg/kg [times]4). Although the recipient developed mixed chimerism (MC), he developed lethal CMV infection by day 19 after BMT. Another recipient received a reduced dose of Thymoglobulin (10mg/kg[times]2) but increased dose of belatacept (20mg/kg [times]6). The recipient developed MC but died due to lymphoma on day 49. All four recipients that received Thymoglobulin (10mg/kg[times]2) and belatacept (20mg/kg [times]4) developed MC without infectious complications or lymphoma and 3/4 achieved long-term renal allograft survival without I.S. (>300 days). The last recipient in this group did not develop rejection but died on day 108 due to a renal allograft biopsy complication.
Conclusion: A clincial applicable conditioning regimen for induction of delayed renal allograft tolerance has been successfully defined in nonhuman primates. 
CITATION INFORMATION: Hotta K, Oura T, Dehnadi A, Boskovic S, Matsunami M, Rosales I, Smith N, Colvin R, Cosimi A, Kawai T. Induction of Delayed Renal Allograft Tolerance Using Only Clinically Available Reagents in Non-Human Primates. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Hotta K, Oura T, Dehnadi A, Boskovic S, Matsunami M, Rosales I, Smith N, Colvin R, Cosimi A, Kawai T. Induction of Delayed Renal Allograft Tolerance Using Only Clinically Available Reagents in Non-Human Primates. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/induction-of-delayed-renal-allograft-tolerance-using-only-clinically-available-reagents-in-non-human-primates/. Accessed November 25, 2024.« Back to 2017 American Transplant Congress