MP30-04 INDUCTION OF DELAYED RENAL ALLOGRAFT TOLERANCE WITH CLINICAL AVAILABLE REAGENTS IN NON-HUMAN PRIMATES

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II1 Apr 2017MP30-04 INDUCTION OF DELAYED RENAL ALLOGRAFT TOLERANCE WITH CLINICAL AVAILABLE REAGENTS IN NON-HUMAN PRIMATES Kiyohiko Hotta, Tetsu Oura, Abbas Dehnadi, Gilles Benichou, A. Benedict Cosimi, and Tatsuo Kawai Kiyohiko HottaKiyohiko Hotta More articles by this author , Tetsu OuraTetsu Oura More articles by this author , Abbas DehnadiAbbas Dehnadi More articles by this author , Gilles BenichouGilles Benichou More articles by this author , A. Benedict CosimiA. Benedict Cosimi More articles by this author , and Tatsuo KawaiTatsuo Kawai More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.937AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We have previously reported successful induction of renal allograft tolerance following a period of conventional immunosuppression (Delayed tolerance) using a nonmyeloablative conditioning with anti-CD154 and anti-CD8 mAbs or LFA3-Ig in MHC-mismatched kidney transplantation (KTx). However, since these reagents are not currently clinically available, the protocol needs to be revised to apply this approach to clinical deceased donor transplantation. In this study, we tested clinically available reagents, CTLA4Ig(belatacept) and rabbit-ATG(Thymoglobulin), for induction of delayed tolerance. METHODS KTx was performed with a 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) with a nonmyeloablative conditioning regimen that consisted of 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×3) and belatacept (20mg/kg ×4). Although the recipient developed mixed chimerism (MC), he died due to lethal CMV on day 19 after BMT. Another recipient received a reduced dose of Thymoglobulin (10mg/kg×2) but increased dose of belatacept (20mg/kg ×6). The recipient developed MC but died due to lymphoma on day 49. All four recipients that received Thymoglobulin (10mg/kg×2) and belatacept (20mg/kg ×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 ischemic kidney injury caused by hypotension during the renal allograft biopsy. CONCLUSIONS Induction of delayed renal allograft tolerance is achieved in nonhuman primates by a nonmyeloablative conditioning with belatacept and Thymoglobulin. This protocol for delayed tolerance is directly applicable to clinical deceased donor kidney transplantation. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e390 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Kiyohiko Hotta More articles by this author Tetsu Oura More articles by this author Abbas Dehnadi More articles by this author Gilles Benichou More articles by this author A. Benedict Cosimi More articles by this author Tatsuo Kawai More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...