Advertisement
Review Article| Volume 39, ISSUE 1, P157-169, March 2019

Novel Targets of Immunosuppression in Transplantation

Published:December 17, 2018DOI:https://doi.org/10.1016/j.cll.2018.10.008

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Agarwal A.
        • Ally W.
        • Brayman K.
        The future direction and unmet needs of transplant immunosuppression.
        Expert Rev Clin Pharmacol. 2016; 9: 873-876
        • Lamb K.E.
        • Lodhi S.
        • Meier-Kriesche H.U.
        Long-term renal allograft survival in the United States: a critical reappraisal.
        Am J Transplant. 2011; 11: 450-462
        • Stegall M.D.
        • Gaston R.S.
        • Cosio F.G.
        • et al.
        Through a glass darkly: seeking clarity in preventing late kidney transplant failure.
        J Am Soc Nephrol. 2015; 26: 20-29
        • Vella J.P.
        • Sayegh M.H.
        Current and future immunosuppressive therapies: impact on chronic allograft dysfunction.
        J Nephrol. 1997; 10: 229-231
        • Aspeslet L.
        • Freitag D.
        • Trepanier D.
        • et al.
        ISA(TX)247: a novel calcineurin inhibitor.
        Transpl Proc. 2001; 33: 1048-1051
        • 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: 2675-2684
        • Wojciechowski D.
        • Vincenti F.
        Tofacitinib in kidney transplantation.
        Expert Opin Investig Drugs. 2013; 22: 1193-1199
        • Busque S.
        • Leventhal J.
        • Brennan D.C.
        • 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: 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: 2446-2456
        • Vincenti F.
        • Silva H.T.
        • Busque S.
        • et al.
        Evaluation of the effect of tofacitinib exposure on outcomes in kidney transplant patients.
        Am J Transplant. 2015; 15: 1644-1653
        • O’Connell P.J.
        • Vincenti B.S.
        Tofacitinib in renal allograft recipients: long-term efficacy and safety in an active-comparator-controlled extension trial.
        Transplantation. 2016; 100: S84-S85
        • Evenou J.P.
        • 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: 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: 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: 156-164
        • Tedesco-Silva H.
        • Kho M.M.
        • Hartmann A.
        • et al.
        Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients.
        Am J Transplant. 2013; 13: 1757-1768
        • Russ G.R.
        • Tedesco-Silva H.
        • Kuypers D.R.
        • et al.
        Efficacy of sotrastaurin plus tacrolimus after de novo kidney transplantation: randomized, phase II trial results.
        Am J Transplant. 2013; 13: 1746-1756
        • Andre P.
        • Prasad K.S.
        • Denis C.V.
        • et al.
        CD40L stabilizes arterial thrombi by a beta3 integrin--dependent mechanism.
        Nat Med. 2002; 8: 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: 1290-1299
        • Vincenti F.Y.H.
        • Klintmalm G.
        • Steinberg S.
        • et al.
        Clinical outcomes in a Phase 1b, randomized, double blinded, parallel group, placebocontrolled, single dose study of ASKP1240 in de novo kidney transplantation.
        Am J Transplant. 2013; 13: 86
        • Harland R.
        • Klintmalm G.
        • Yang H.
        • et al.
        ASKP1240 in de novo kidney transplant recipients.
        Am J Transplant. 2015; 15
        • Liu D.
        • Krummey S.M.
        • Badell I.R.
        • et al.
        2B4 (CD244) induced by selective CD28 blockade functionally regulates allograft-specific CD8+ T cell responses.
        J Exp Med. 2014; 211: 297-311
        • Adams A.B.
        • Ford M.L.
        • Larsen C.P.
        Costimulation blockade in autoimmunity and transplantation: the CD28 pathway.
        J Immunol. 2016; 197: 2045-2050
        • Poirier N.
        • Dilek N.
        • Mary C.
        • et al.
        FR104, an antagonist anti-CD28 monovalent fab' antibody, prevents alloimmunization and allows calcineurin inhibitor minimization in nonhuman primate renal allograft.
        Am J Transplant. 2015; 15: 88-100
        • Kawai T.
        • Cosimi A.B.
        • Spitzer T.R.
        • et al.
        HLA-mismatched renal transplantation without maintenance immunosuppression.
        N Engl J Med. 2008; 358: 353-361
        • Pruett T.L.
        • McGory R.W.
        • Wright F.H.
        • et al.
        Safety profile, pharmacokinetics, and pharmacodynamics of siplizumab, a humanized anti-CD2 monoclonal antibody, in renal allograft recipients.
        Transplant Proc. 2009; 41: 3655-3661
        • Getts D.R.
        • Kramer W.G.
        • Wiseman A.C.
        • et al.
        The pharmacokinetics and pharmacodynamics of TOL101, a murine IgM anti-human alphabeta T cell receptor antibody, in renal transplant patients.
        Clin Pharmacokinet. 2014; 53: 649-657
        • Flechner S.M.
        • Mulgoankar S.
        • Melton L.B.
        • et al.
        First-in-human study of the safety and efficacy of TOL101 induction to prevent kidney transplant rejection.
        Am J Transplant. 2014; 14: 1346-1355
        • 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: 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: 1724-1733
        • Sautenet B.
        • Blancho G.
        • Buchler M.
        • et al.
        One-year results of the effects of rituximab on acute antibody-mediated rejection in renal transplantation: RITUX ERAH, a multicenter double-blind randomized placebo-controlled trial.
        Transplantation. 2016; 100: 391-399
        • Ai J.
        • Advani A.
        Current status of antibody therapy in ALL.
        Br J Haematol. 2015; 168: 471-480
        • Bachanova V.
        • Frankel A.E.
        • Cao Q.
        • et al.
        Phase I study of a bispecific ligand-directed toxin targeting CD22 and CD19 (DT2219) for refractory B-cell malignancies.
        Clin Cancer Res. 2015; 21: 1267-1272
        • Mancianti N.
        • Monaci G.
        • Rollo F.
        • et al.
        First case report of using Ofatumumab in kidney transplantation AB0 incompatible.
        G Ital Nefrol. 2017; 34 ([pii:2017-vol6])
        • Ye Q.
        • Wang L.
        • Wells A.D.
        • et al.
        BAFF binding to T cell-expressed BAFF-R costimulates T cell proliferation and alloresponses.
        Eur J Immunol. 2004; 34: 2750-2759
        • Parsons R.F.
        • Yu M.
        • Vivek K.
        • et al.
        Murine islet allograft tolerance upon blockade of the B-lymphocyte stimulator, BLyS/BAFF.
        Transplantation. 2012; 93: 676-685
        • Thibault-Espitia A.
        • Foucher Y.
        • Danger R.
        • et al.
        BAFF and BAFF-R levels are associated with risk of long-term kidney graft dysfunction and development of donor-specific antibodies.
        Am J Transplant. 2012; 12: 2754-2762
        • Banham G.
        • Prezzi D.
        • Harford S.
        • et al.
        Elevated pretransplantation soluble BAFF is associated with an increased risk of acute antibody-mediated rejection.
        Transplantation. 2013; 96: 413-420
        • Banham G.D.
        • Flint S.M.
        • Torpey N.
        • et al.
        Belimumab in kidney transplantation: an experimental medicine, randomised, placebo-controlled phase 2 trial.
        Lancet. 2018; 391: 2619-2630
        • Dorner T.
        • Kaufmann J.
        • Wegener W.A.
        • et al.
        Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus.
        Arthritis Res Ther. 2006; 8: R74
        • Winstedt L.
        • Jarnum S.
        • Nordahl E.A.
        • et al.
        Complete removal of extracellular IgG antibodies in a randomized dose-escalation phase I study with the bacterial enzyme IdeS--a novel therapeutic opportunity.
        PLoS One. 2015; 10: e0132011
        • Jarnum S.
        • Bockermann R.
        • Runstrom A.
        • et al.
        The bacterial enzyme IdeS cleaves the IgG-type of B cell receptor (BCR), abolishes BCR-mediated cell signaling, and inhibits memory B cell activation.
        J Immunol. 2015; 195: 5592-5601
        • Lonze B.E.
        • Tatapudi V.S.
        • Weldon E.P.
        • et al.
        IdeS (Imlifidase): a novel agent that cleaves human IgG and permits successful kidney transplantation across high-strength donor-specific antibody.
        Ann Surg. 2018; 268: 488-496
        • Vincenti F.
        • Rostaing L.
        • Grinyo J.
        • et al.
        Belatacept and long-term outcomes in kidney transplantation.
        N Engl J Med. 2016; 374: 333-343
        • de Graav G.N.
        • Dieterich M.
        • Hesselink D.A.
        • et al.
        Follicular T helper cells and humoral reactivity in kidney transplant patients.
        Clin Exp Immunol. 2015; 180: 329-340
        • Topp M.S.
        • Gokbuget N.
        • Zugmaier G.
        • et al.
        Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL.
        Blood. 2012; 120: 5185-5187
        • Fichou N.
        • Gouard S.
        • Maurel C.
        • et al.
        Single-dose anti-CD138 radioimmunotherapy: bismuth-213 is more efficient than Lutetium-177 for treatment of multiple myeloma in a preclinical model.
        Front Med (Lausanne). 2015; 2: 76
        • Vo A.A.
        • Choi J.
        • Kim I.
        • et al.
        A phase I/II trial of the interleukin-6 receptor-specific humanized monoclonal (Tocilizumab) + intravenous immunoglobulin in difficult to desensitize patients.
        Transplantation. 2015; 99: 2356-2363
        • Chu V.T.
        • Frohlich A.
        • Steinhauser G.
        • et al.
        Eosinophils are required for the maintenance of plasma cells in the bone marrow.
        Nat Immunol. 2011; 12: 151-159
        • Pavord I.D.
        • Korn S.
        • Howarth P.
        • et al.
        Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial.
        Lancet. 2012; 380: 651-659
        • Varricchi G.
        • Bagnasco D.
        • Borriello F.
        • et al.
        Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs.
        Curr Opin Allergy Clin Immunol. 2016; 16: 186-200
        • Kwun J.
        • Page E.
        • Hong J.J.
        • et al.
        Neutralizing BAFF/APRIL with atacicept prevents early DSA formation and AMR development in T cell depletion induced nonhuman primate AMR model.
        Am J Transplant. 2015; 15: 815-822
        • Mujtaba M.A.
        • Komocsar W.J.
        • Nantz E.
        • et al.
        Effect of treatment with tabalumab, a B Cell-activating factor inhibitor, on highly sensitized patients with end-stage renal disease awaiting transplantation.
        Am J Transplant. 2016; 16: 1266-1275
        • Stegall M.D.
        • Chedid M.F.
        • Cornell L.D.
        The role of complement in antibody-mediated rejection in kidney transplantation.
        Nat Rev Nephrol. 2012; 8: 670-678
        • Ward P.A.
        The harmful role of c5a on innate immunity in sepsis.
        J Innate Immun. 2011; 2: 439-445
        • Stegall M.D.
        • Diwan T.
        • Raghavaiah S.
        • et al.
        Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients.
        Am J Transplant. 2011; 11: 2405-2413
        • Bentall A.
        • Tyan D.B.
        • Sequeira F.
        • et al.
        Antibody-mediated rejection despite inhibition of terminal complement.
        Transpl Int. 2014; 27: 1235-1243
        • Eskandary F.
        • Jilma B.
        • Muhlbacher J.
        • et al.
        Anti-C1s monoclonal antibody BIVV009 in late antibody-mediated kidney allograft rejection-results from a first-in-patient phase 1 trial.
        Am J Transplant. 2018; 18: 916-926
        • Davis 3rd, A.E.
        • Lu F.
        • Mejia P.
        C1 inhibitor, a multi-functional serine protease inhibitor.
        Thromb Haemost. 2010; 104: 886-893
        • Montgomery R.A.
        • Orandi B.J.
        • Racusen L.
        • et al.
        Plasma-derived C1 esterase inhibitor for acute antibody-mediated rejection following kidney transplantation: results of a randomized double-blind placebo-controlled pilot study.
        Am J Transplant. 2016; 16: 3468-3478
      1. Behring C. Efficacy and safety of human plasma-derived C1-esterase inhibitor as add-on to standard of care for the treatment of refractory Antibody Mediated Rejection (AMR) in adult renal transplant recipients (NCT03221842). 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03221842.

      2. Shire. A multicenter study to evaluate the efficacy and safety of Cinryze® for the treatment of acute antibody-mediated rejection in participants with kidney transplant(ClinicalTrials.gov Identifier: NCT02547220). 2015. Available at: https://clinicaltrials.gov/ct2/show/NCT02547220.