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Review

Emerging drugs for prevention of T-cell mediated rejection in liver and kidney transplantation

, &
Pages 123-136 | Received 31 May 2016, Accepted 12 May 2017, Published online: 22 May 2017

References

  • WHO. Global knowledge base on transplantation; 2008. Available from: http://www.who.int/transplantation/gkt/statistics/en/.
  • Sharing UNoO. OPTN/SRTR annual data report; 2012. Available from: http://srtr.transplant.hrsa.gov/annual_reports/2012/pdf/2012_SRTR_ADR_updated_full_intro.pdf
  • Vincenti F, Schena FP, Paraskevas S, et al. A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients. Am J Transplant. 2008;8(2):307–316.
  • Kramer BK, Klinger M, Vitko S, et al. Tacrolimus-based, steroid-free regimens in renal transplantation: 3-year follow-up of the ATLAS trial. Transplantation. 2012;94(5):492–498.
  • Liefeldt L, Brakemeier S, Glander P, et al. Donor-specific HLA antibodies in a cohort comparing everolimus with cyclosporine after kidney transplantation. Am J Transplant. 2012;12(5):1192–1198.
  • Isakova T, Xie H, Messinger S, et al. Inhibitors of mTOR and risks of allograft failure and mortality in kidney transplantation. Am J Transplant. 2013;13(1):100–110.
  • Guerra G, Ciancio G, Gaynor JJ, et al. Randomized trial of immunosuppressive regimens in renal transplantation. J Am Soc Nephrol. 2011;22(9):1758–1768.
  • Pascual J, Zamora J, Galeano C, et al. Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev. 2009;1:Cd005632.
  • Pascual J, Royuela A, Galeano C, et al. Very early steroid withdrawal or complete avoidance for kidney transplant recipients: a systematic review. Nephrol Dial Transplant. 2012;27(2):825–832.
  • Mujtaba MA, Taber TE, Goggins WC, et al. Early steroid withdrawal in repeat kidney transplantation. Clin J Am Soc Nephrol. 2011;6(2):404–411.
  • Thomusch O, Wiesener M, Opgenoorth M, et al. Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (Harmony): an open-label, multicentre, randomised controlled trial. Lancet. 2016;388(10063):3006–3016.
  • Hoshino J, Kaneku H, Everly MJ, et al. Using donor-specific antibodies to monitor the need for immunosuppression. Transplantation. 2012;93(11):1173–1178.
  • Delgado JC, Fuller A, Ozawa M, et al. No occurrence of de novo HLA antibodies in patients with early corticosteroid withdrawal in a 5-year prospective randomized study. Transplantation. 2009;87(4):546–548.
  • Campsen J, Zimmerman MA, Trotter JF, et al. Liver transplantation for autoimmune hepatitis and the success of aggressive corticosteroid withdrawal. Liver Transpl. 2008;14(9):1281–1286.
  • Gomez R, Moreno E, Colina F, et al. Steroid withdrawal is safe and beneficial in stable cyclosporine-treated liver transplant patients. J Hepatol. 1998;28(1):150–156.
  • Reding R. Steroid withdrawal in liver transplantation: benefits, risks, and unanswered questions. Transplantation. 2000;70(3):405–410.
  • Kim JM, Joh JW, Kim SJ, et al. Steroid withdrawal in adult liver transplantation: occurrence at a single center. Transplant Proc. 2010;42(10):4132–4136.
  • Lerut JP, Pinheiro RS, Lai Q, et al. Is minimal, [almost] steroid-free immunosuppression a safe approach in adult liver transplantation? Long-term outcome of a prospective, double blind, placebo-controlled, randomized, investigator-driven study. Ann Surg. 2014;260(5):886-91;discussion 91–2.
  • Fairfield C, Penninga L, Powell J, et al. Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients. Cochrane Database Syst Rev. 2015;12:Cd007606.
  • Karie-Guigues S, Janus N, Saliba F, et al. Long-term renal function in liver transplant recipients and impact of immunosuppressive regimens (calcineurin inhibitors alone or in combination with mycophenolate mofetil): the TRY study. Liver Transpl. 2009;15(9):1083–1091.
  • Boudjema K, Camus C, Saliba F, et al. Reduced-dose tacrolimus with mycophenolate mofetil vs. standard-dose tacrolimus in liver transplantation: a randomized study. Am J Transplant. 2011;11(5):965–976.
  • Gaston RS, Kaplan B, Shah T, et al. Fixed- or controlled-dose mycophenolate mofetil with standard- or reduced-dose calcineurin inhibitors: the opticept trial. Am J Transplant. 2009;9(7):1607–1619.
  • van Gelder TS, Tedesco H, de Fijter H, et al.; for FDCC Study Group. RA prospective, randomized study comparing fixed dose versus concentration controlled MMF regimens For de novo patients following renal transplantation (The FDCC trial). Transplantation. 2006;82(1):343.
  • Calne RY, White DJ, Thiru S, et al. Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet. 1978;2(8104–5):1323–1327.
  • Calne RY, Rolles K, White DJ, et al. Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet. 1979;2(8151):1033–1036.
  • Emmel EA, Verweij CL, Durand DB, et al. Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science. 1989;246(4937):1617–1620.
  • Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol. 2005;5(6):472–484.
  • Canadian Multicentre Transplant Study Group. A randomized clinical trial of cyclosporine in cadaveric renal transplantation. N Engl J Med. 1983;309(14):809–815.
  • Canadian Multicentre Transplant Study Group. A randomized clinical trial of cyclosporine in cadaveric renal transplantation. Analysis at three years. N Engl J Med. 1986;314(19):1219–1225.
  • Ponticelli C, Minetti L, Di Palo FQ, et al. The Milan clinical trial with cyclosporine in cadaveric renal transplantation. A three-year follow-up. Transplantation. 1988;45(5):908–913.
  • Isoniemi HM, Ahonen J, Tikkanen MJ, et al. Long-term consequences of different immunosuppressive regimens for renal allografts. Transplantation. 1993;55(3):494–499.
  • Pirsch JD, Miller J, Deierhoi MH, et al. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group. Transplantation. 1997;63(7):977–983.
  • Johnson C, Ahsan N, Gonwa T, et al. Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation. Transplantation. 2000;69(5):834–841.
  • Ahsan N, Johnson C, Gonwa T, et al. Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years. Transplantation. 2001;72(2):245–250.
  • Margreiter R. Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. Lancet. 2002;359(9308):741–746.
  • Gonwa T, Johnson C, Ahsan N, et al. Randomized trial of tacrolimus + mycophenolate mofetil or azathioprine versus cyclosporine + mycophenolate mofetil after cadaveric kidney transplantation: results at three years. Transplantation. 2003;75(12):2048–2053.
  • Kramer BK, Montagnino G, Del Castillo D, et al. Efficacy and safety of tacrolimus compared with cyclosporin A microemulsion in renal transplantation: 2 year follow-up results. Nephrol Dial Transplant. 2005;20(5):968–973.
  • Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med. 2007;357(25):2562–2575.
  • Webster A, Woodroffe RC, Taylor RS, et al. Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients. Cochrane Database Syst Rev. 2005;4:Cd003961.
  • O’Grady JG, Burroughs A, Hardy P, et al. Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial. Lancet. 2002;360(9340):1119–1125.
  • O’Grady JG, Hardy P, Burroughs AK, et al. Randomized controlled trial of tacrolimus versus microemulsified cyclosporin (TMC) in liver transplantation: poststudy surveillance to 3 years. Am J Transplant. 2007;7(1):137–141.
  • Haddad EM, McAlister VC, Renouf E, et al. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst Rev. 2006;4:Cd005161.
  • Kim W, Smith J, Skeans M, et al. OPTN/SRTR 2012 annual data report: liver. Am J Transplant. 2014;14(Suppl 1):69–98.
  • Matas AJ, Smith JM, Skeans MA, et al. OPTN/SRTR 2013 annual data report: kidney. Am J Transplant. 2015;15(Suppl 2):1–34.
  • Prendergast MB, Gaston RS. Optimizing medication adherence: an ongoing opportunity to improve outcomes after kidney transplantation. Clin J Am Soc Nephrol. 2010;5(7):1305–1311.
  • Patel P, Patel H, Panchal S, et al. Formulation strategies for drug delivery of tacrolimus: an overview. Int J Pharm Investig. 2012;2(4):169–175.
  • Ho ET, Wong G, Craig JC, et al. Once-daily extended-release versus twice-daily standard-release tacrolimus in kidney transplant recipients: a systematic review. Transplantation. 2013;95(9):1120–1128.
  • Beckebaum S, Iacob S, Sweid D, et al. Efficacy, safety, and immunosuppressant adherence in stable liver transplant patients converted from a twice-daily tacrolimus-based regimen to once-daily tacrolimus extended-release formulation. Transpl Int. 2011;24(7):666–675.
  • Doesch AO, Mueller S, Akyol C, et al. Increased adherence eight months after switch from twice daily calcineurin inhibitor based treatment to once daily modified released tacrolimus in heart transplantation. Drug Des Devel Ther. 2013;7:1253–1258.
  • Silva HT Jr., Yang HC, Abouljoud M, et al. One-year results with extended-release tacrolimus/MMF, tacrolimus/MMF and cyclosporine/MMF in de novo kidney transplant recipients. Am J Transplant. 2007;7(3):595–608.
  • Silva HT Jr., Yang HC, Meier-Kriesche HU, et al. Long-term follow-up of a phase III clinical trial comparing tacrolimus extended-release/MMF, tacrolimus/MMF, and cyclosporine/MMF in de novo kidney transplant recipients. Transplantation. 2014;97(6):636–641.
  • Kramer BK, Charpentier B, Backman L, et al. Tacrolimus once daily (ADVAGRAF) versus twice daily (PROGRAF) in de novo renal transplantation: a randomized phase III study. Am J Transplant. 2010;10(12):2632–2643.
  • Yang SS, Choi JY, Cho WT, et al. A single center, open-label, randomized pilot study to evaluate the safety and efficacy of tacrolimus modified release, Advagraf, versus tacrolimus twice daily, Prograf, in stable renal recipients (single). Transplant Proc. 2015;47(3):617–621.
  • Patel N, Cook A, Greenhalgh E, et al. Overview of extended release tacrolimus in solid organ transplantation. World J Transplant. 2016;6(1):144–154.
  • Trunecka P, Boillot O, Seehofer D, et al. Once-daily prolonged-release tacrolimus (ADVAGRAF) versus twice-daily tacrolimus (PROGRAF) in liver transplantation. Am J Transplant. 2010;10(10):2313–2323.
  • Adam R, Karam V, Delvart V, et al. Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European liver transplant registry. Am J Transplant. 2015;15(5):1267–1282.
  • Florman S, Alloway R, Kalayoglu M, et al. Conversion of stable liver transplant recipients from a twice-daily Prograf-based regimen to a once-daily modified release tacrolimus-based regimen. Transplant Proc. 2005;37(2):1211–1213.
  • Dopazo C, Rodriguez R, Llado L, et al. Successful conversion from twice-daily to once-daily tacrolimus in liver transplantation: observational multicenter study. Clin Transplant. 2012;26(1):E32–7.
  • Gaber AO, Alloway RR, Bodziak K, et al. Conversion from twice-daily tacrolimus capsules to once-daily extended-release tacrolimus (LCPT): a phase 2 trial of stable renal transplant recipients. Transplantation. 2013;96(2):191–197.
  • Alloway RR, Eckhoff DE, Washburn WK, et al. Conversion from twice daily tacrolimus capsules to once daily extended-release tacrolimus (LCP-Tacro): phase 2 trial of stable liver transplant recipients. Liver Transpl. 2014;20(5):564–575.
  • Budde K, Bunnapradist S, Grinyo JM, et al. Novel once-daily extended-release tacrolimus (LCPT) versus twice-daily tacrolimus in de novo kidney transplants: one-year results of Phase III, double-blind, randomized trial. Am J Transplant. 2014;14(12):2796–2806.
  • Rostaing L, Bunnapradist S, Grinyo JM, et al. Novel once-daily extended-release tacrolimus versus twice-daily tacrolimus in de novo kidney transplant recipients: two-year results of phase 3, double-blind, randomized trial. Am J Kidney Dis. 2016;67(4):648–659.
  • Bunnapradist S, Ciechanowski K, West-Thielke P, et al. Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial. Am J Transplant. 2013;13(3):760–769.
  • Bunnapradist S, Rostaing L, Alloway RR, et al. LCPT once-daily extended-release tacrolimus tablets versus twice-daily capsules: a pooled analysis of two phase 3 trials in important de novo and stable kidney transplant recipient subgroups. Transpl Int. 2016;29(5):603–611.
  • Kauffman HM, Cherikh WS, Cheng Y, et al. Maintenance immunosuppression with target-of-rapamycin inhibitors is associated with a reduced incidence of de novo malignancies. Transplantation. 2005;80(7):883–889.
  • Ventura-Aguiar P, Campistol JM, Diekmann F. Safety of mTOR inhibitors in adult solid organ transplantation. Expert Opin Drug Saf. 2016;15(3):303–319.
  • Flechner SM, Glyda M, Cockfield S, et al. The ORION study: comparison of two sirolimus-based regimens versus tacrolimus and mycophenolate mofetil in renal allograft recipients. Am J Transplant. 2011;11(8):1633–1644.
  • Buchler M, Caillard S, Barbier S, et al. Sirolimus versus cyclosporine in kidney recipients receiving thymoglobulin, mycophenolate mofetil and a 6-month course of steroids. Am J Transplant. 2007;7(11):2522–2531.
  • Nashan B, Curtis J, Ponticelli C, et al. Everolimus and reduced-exposure cyclosporine in de novo renal-transplant recipients: a three-year phase II, randomized, multicenter, open-label study. Transplantation. 2004;78(9):1332–1340.
  • Lim WH, Eris J, Kanellis J, et al. A systematic review of conversion from calcineurin inhibitor to mammalian target of rapamycin inhibitors for maintenance immunosuppression in kidney transplant recipients. Am J Transplant. 2014;14(9):2106–2119.
  • Croze LE, Tetaz R, Roustit M, et al. Conversion to mammalian target of rapamycin inhibitors increases risk of de novo donor-specific antibodies. Transpl Int. 2014;27(8):775–783.
  • Kawahara T, Asthana S, Kneteman NM. m-TOR inhibitors: what role in liver transplantation? J Hepatol. 2011;55(6):1441–1451.
  • De Simone P, Nevens F, De Carlis L, et al. Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial. Am J Transplant. 2012;12(11):3008–3020.
  • Saliba F, De Simone P, Nevens F, et al. Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study. Am J Transplant. 2013;13(7):1734–1745.
  • Fischer L, Saliba F, Kaiser GM, et al. Three-year outcomes in de novo liver transplant patients receiving everolimus with reduced tacrolimus: follow-up results from a randomized, multicenter study. Transplantation. 2015;99(7):1455–1462.
  • Sterneck M, Kaiser GM, Heyne N, et al. Everolimus and early calcineurin inhibitor withdrawal: 3-year results from a randomized trial in liver transplantation. Am J Transplant. 2014;14(3):701–710.
  • Matter MS, Decaens T, Andersen JB, et al. Targeting the mTOR pathway in hepatocellular carcinoma: current state and future trends. J Hepatol. 2014;60(4):855–865.
  • Masetti M, Montalti R, Rompianesi G, et al. Early withdrawal of calcineurin inhibitors and everolimus monotherapy in de novo liver transplant recipients preserves renal function. Am J Transplant. 2010;10(10):2252–2262.
  • Fischer L, Klempnauer J, Beckebaum S, et al. A randomized, controlled study to assess the conversion from calcineurin-inhibitors to everolimus after liver transplantation–PROTECT. Am J Transplant. 2012;12(7):1855–1865.
  • Duvoux C, Toso C. mTOR inhibitor therapy: does it prevent HCC recurrence after liver transplantation? Transplant Rev (Orlando). 2015;29(3):168–174.
  • Geissler EK, Schnitzbauer AA, Zulke C, et al. Sirolimus use in liver transplant recipients with hepatocellular carcinoma: a randomized, multicenter, open-label phase 3 trial. Transplantation. 2016;100(1):116–125.
  • Scientific registry of transplant recipients; 2015. Available from: http://www.SRTR.org
  • Barber K, Blackwell J, Collett D, et al. Life expectancy of adult liver allograft recipients in the UK. Gut. 2007;56(2):279–282.
  • Gelson W, Hoare M, Dawwas MF, et al. The pattern of late mortality in liver transplant recipients in the United Kingdom. Transplantation. 2011;91(11):1240–1244.
  • Ojo AO, Hanson JA, Wolfe RA, et al. Long-term survival in renal transplant recipients with graft function. Kidney Int. 2000;57(1):307–313.
  • Matas AJ, Gillingham KJ, Humar A, et al. 2202 Kidney transplant recipients with 10 years of graft function: what happens next? Am J Transplant. 2008;8(11):2410–2419.
  • Levitsky J. Operational tolerance: past lessons and future prospects. Liver Transpl. 2011;17(3):222–232.
  • Sellares J, de Freitas DG, Mengel M, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12(2):388–399.
  • El-Zoghby ZM, Stegall MD, Lager DJ, et al. Identifying specific causes of kidney allograft loss. Am J Transplant. 2009;9(3):527–535.
  • Hricik DE, Formica RN, Nickerson P, et al. Adverse outcomes of tacrolimus withdrawal in immune-quiescent kidney transplant recipients. J Am Soc Nephrol. 2015;26(12):3114–3122.
  • Vincenti F, Larsen C, Durrbach A, et al. Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005;353(8):770–781.
  • Vincenti F, Charpentier B, Vanrenterghem Y, et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant. 2010;10(3):535–546.
  • Vincenti F, Rostaing L, Grinyo J, et al. Belatacept and long-term outcomes in kidney transplantation. N Engl J Med. 2016;374(4):333–343.
  • Durrbach A, Pestana JM, Florman S, et al. Long-term outcomes in belatacept- versus cyclosporine-treated recipients of extended criteria donor kidneys: final results from BENEFIT-EXT, a phase III randomized study. Am J Transplant. 2016;16(11):3192–3201.
  • Masson P, Henderson L, Chapman JR, et al. Belatacept for kidney transplant recipients. Cochrane Database Syst Rev. 2014;11:Cd010699.
  • Klintmalm GB, Feng S, Lake JR, et al. Belatacept-based immunosuppression in de novo liver transplant recipients: 1-year experience from a phase II randomized study. Am J Transplant. 2014;14(8):1817–1827.
  • Knechtle SJ, Adams AB. Belatacept: is there BENEFIT for liver transplantation too? Am J Transplant. 2014;14(8):1717–1718.
  • Xia MQ, Hale G, Lifely MR, et al. Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis. Biochem J. 1993;293(Pt 3):633–640.
  • Laftavi MR, Sharma R, Feng L, et al. Induction therapy in renal transplant recipients: a review. Immunol Invest. 2014;43(8):790–806.
  • Morgan RD, O’Callaghan JM, Knight SR, et al. Alemtuzumab induction therapy in kidney transplantation: a systematic review and meta-analysis. Transplantation. 2012;93(12):1179–1188.
  • Haynes R, Harden P, Judge P, et al. Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet. 2014;384(9955):1684–1690.
  • Levitsky J, Thudi K, Ison MG, et al. Alemtuzumab induction in non-hepatitis C positive liver transplant recipients. Liver Transpl. 2011;17(1):32–37.
  • Aspeslet L, Freitag D, Trepanier D, et al. ISA(TX)247: a novel calcineurin inhibitor. Transplant Proc. 2001;33(1–2):1048–1051.
  • Vincenti F, Kirk AD. What’s next in the pipeline. Am J Transplant. 2008;8(10):1972–1981.
  • Busque S, Cantarovich M, Mulgaonkar S, et al. The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation. Am J Transplant. 2011;11(12):2675–2684.
  • Wojciechowski D, Vincenti F. Tofacitinib in kidney transplantation. Expert Opin Investig Drugs. 2013;22(9):1193–1199.
  • Busque S, Leventhal J, Brennan DC, et al. Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP-690,550: a pilot study in de novo kidney allograft recipients. Am J Transplant. 2009;9(8):1936–1945.
  • Vincenti F, Tedesco Silva H, Busque S, et al. Randomized phase 2b trial of tofacitinib (CP-690,550) in de novo kidney transplant patients: efficacy, renal function and safety at 1 year. Am J Transplant. 2012;12(9):2446–2456.
  • Vincenti F, Silva HT, Busque S, et al. Evaluation of the effect of tofacitinib exposure on outcomes in kidney transplant patients. Am J Transplant. 2015;15(6):1644–1653.
  • O’Connell PJ, Busque S, Vincenti F, et al. Tofacitinib in renal allograft recipients: long-term efficacy and safety in an active-comparator-controlled extension trial [abstract]. Transplantation. 2016;100(7s):S84-85.
  • Evenou JP, Wagner J, Zenke G, et al. The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activation. J Pharmacol Exp Ther. 2009;330(3):792–801.
  • Weckbecker G, Pally C, Beerli C, et al. Effects of the novel protein kinase C inhibitor AEB071 (Sotrastaurin) on rat cardiac allograft survival using single agent treatment or combination therapy with cyclosporine, everolimus or FTY720. Transpl Int. 2010;23(5):543–552.
  • Bigaud M, Wieczorek G, Beerli C, et al. Sotrastaurin (AEB071) alone and in combination with cyclosporine A prolongs survival times of non-human primate recipients of life-supporting kidney allografts. Transplantation. 2012;93(2):156–164.
  • Tedesco-Silva H, Kho MM, Hartmann A, et al. Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients. Am J Transplant. 2013;13(7):1757–1768.
  • Pascher A, De Simone P, Pratschke J, et al. Protein kinase C inhibitor sotrastaurin in de novo liver transplant recipients: a randomized phase II trial. Am J Transplant. 2015;15(5):1283–1292.
  • Andre P, Prasad KS, Denis CV, et al. CD40L stabilizes arterial thrombi by a beta3 integrin–dependent mechanism. Nat Med. 2002;8(3):247–252.
  • Okimura K, Maeta K, Kobayashi N, et al. Characterization of ASKP1240, a fully human antibody targeting human CD40 with potent immunosuppressive effects. Am J Transplant. 2014;14(6):1290–1299.
  • Vincenti FYH, Klintmalm G, Steinberg S, et al. Clinical outcomes in a Phase 1b, randomized, double blinded, parallel group, placebo-controlled, single dose study of ASKP1240 in de novo kidney transplantation [abstract]. Am J Transplant. 2013;13(Supp5):86.
  • Harland R, Klintmalm G, Yang H, et al. ASKP1240 in de novo kidney transplant recipients [abstract]. Am J Transplant. 2015;15(supp 3).
  • Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat Rev Immunol. 2003;3(3):199–210.
  • Trzonkowski P, Bieniaszewska M, Juscinska J, et al. First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+CD25+CD127- T regulatory cells. Clin Immunol. 2009;133(1):22–26.
  • Brunstein CG, Miller JS, Cao Q, et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2011;117(3):1061–1070.
  • Di Ianni M, Falzetti F, Carotti A, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011;117(14):3921–3928.
  • Martelli MF, Di Ianni M, Ruggeri L, et al. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014;124(4):638–644.
  • Marek-Trzonkowska N, Mysliwiec M, Dobyszuk A, et al. Administration of CD4+CD25highCD127- regulatory T cells preserves beta-cell function in type 1 diabetes in children. Diabetes Care. 2012;35(9):1817–1820.
  • Tang Q, Lee K. Regulatory T-cell therapy for transplantation: how many cells do we need? Curr Opin Organ Transplant. 2012;17(4):349–354.
  • Graca L, Thompson S, Lin CY, et al. Both CD4(+)CD25(+) and CD4(+)CD25(-) regulatory cells mediate dominant transplantation tolerance. J Immunol. 2002;168(11):5558–5565.
  • Hu M, Wang C, Zhang GY, et al. Infiltrating Foxp3(+) regulatory T cells from spontaneously tolerant kidney allografts demonstrate donor-specific tolerance. Am J Transplant. 2013;13(11):2819–2830.
  • Putnam AL, Safinia N, Medvec A, et al. Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation. Am J Transplant. 2013;13(11):3010–3020.
  • Geissler EK. The ONE Study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells. Transplant Res. 2012;1(1):11.
  • Benitez C, Londono MC, Miquel R, et al. Prospective multicenter clinical trial of immunosuppressive drug withdrawal in stable adult liver transplant recipients. Hepatology. 2013;58(5):1824–1835.
  • Todo S, Yamashita K, Goto R, et al. A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation. Hepatology. 2016;64(2):632–643.
  • Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363(9419):1439–1441.
  • Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371(9624):1579–1586.
  • Perico N, Casiraghi F, Introna M, et al. Autologous mesenchymal stromal cells and kidney transplantation: a pilot study of safety and clinical feasibility. Clin J Am Soc Nephrol. 2011;6(2):412–422.
  • Tan J, Wu W, Xu X, et al. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA. 2012;307(11):1169–1177.
  • Vanikar AV, Trivedi HL, Feroze A, et al. Effect of co-transplantation of mesenchymal stem cells and hematopoietic stem cells as compared to hematopoietic stem cell transplantation alone in renal transplantation to achieve donor hypo-responsiveness. Int Urol Nephrol. 2011;43(1):225–232.
  • Vanikar AV, Trivedi HL. Stem cell transplantation in living donor renal transplantation for minimization of immunosuppression. Transplantation. 2012;94(8):845–850.
  • Soeder Y, Loss M, Johnson CL, et al. First-in-human case study: multipotent adult progenitor cells for immunomodulation after liver transplantation. Stem Cells Transl Med. 2015;4(8):899–904.
  • Popp FC, Fillenberg B, Eggenhofer E, et al. Safety and feasibility of third-party multipotent adult progenitor cells for immunomodulation therapy after liver transplantation–a phase I study (MISOT-I). J Transl Med. 2011;9:124.
  • Adams DH, Sanchez-Fueyo A, Samuel D. From immunosuppression to tolerance. J Hepatol. 2015;62(1 Suppl):S170–85.
  • Vincenti F, Mendez R, Pescovitz M, et al. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Am J Transplant. 2007;7(7):1770–1777.
  • Rostaing L, Charpentier B, Glyda M, et al. Alefacept combined with tacrolimus, mycophenolate mofetil and steroids in de novo kidney transplantation: a randomized controlled trial. Am J Transplant. 2013;13(7):1724–1733.

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