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Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs

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Pages 651-665 | Received 11 Apr 2021, Accepted 31 Jul 2021, Published online: 20 Aug 2021

References

  • Castelli R, Cannavò A, Conforti F, et al. Immunomodulatory drugs in multiple myeloma: from molecular mechanisms of action to clinical practice. Immunopharmacol Immunotoxicol. 2012;34(5):740–753.
  • Pastural M, Abtahi M, Lang P. The benefits of new immunosuppressive treatments in adult kidney transplantation. Presse Med. 2002;31(9):421–426.
  • Roussey ‐Kesler G, Giral M, Moreau A, et al. Clinical operational tolerance after kidney transplantation. Am J Transplant. 2006;6(4):736–746.
  • Kumbala D, Zhang R. Essential concept of transplant immunology for clinical practice. World J Transplant. 2013;3(4):113–118.
  • Halloran P. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004;351(26):2715–2729.
  • Lakkis FG, Sayegh M. Memory T cells: a hurdle to immunologic tolerance. J Am Soc Nephrol. 2003;14(9):2402–2410.
  • Dinavahi R, George A, Tretin A, et al. Antibodies reactive to non-HLA antigens in transplant glomerulopathy. J Am Soc Nephrol. 2011;22(6):1168–1178.
  • Porcheray F, DeVito J, Yeap BY, et al. Chronic humoral rejection of human kidney allografts associates with broad autoantibody responses. Transplantation. 2010;89(10):1239–1246.
  • Montgomery R. Renal transplantation across HLA and ABO antibody barriers: integrating paired donation into desensitization protocols. Am J Transplant. 2010;10(3):449–457.
  • Warren EH, Greenberg PD, Riddell SRJB. The journal of the American society of hematology. Cytotoxic T-lymphocyte–defined human minor histocompatibility antigens with a restricted tissue distribution. Blood. 1998;91(6):2197–2207.
  • Oynebraten I. Involvement of autophagy in MHC class I antigen presentation. Scand J Immunol. 2020;92(5):e12978.
  • Schutz C, Zoso A, Peng S, et al. MHC-Ig induces memory T cell formation in vivo and inhibits tumour growth. Immun Inflamm Dis. 2014;2(3):181–192.
  • Korkmaz D, Kum S. Investigation of the antigen recognition and presentation capacity of pecteneal hyalocytes in the chicken (Gallus gallus domesticus). Biotech Histochem. 2016;91(3):212–219.
  • Abolnezhadian F, Dehghani R, Dehnavi S, et al. A novel mutation in RFXANK gene and low B cell count in a patient with MHC class II deficiency: a case report. Immunol Res. 2020;68(4):225–231.
  • Janeway C, Murphy KP, Travers P, et al. Janeway's immuno biology. New York, NY: Garland Science; 2008.
  • Tasdemir S, Parlakpinar H, Vardi N, et al. Effect of endogen-exogenous melatonin and erythropoietin on dinitrobenzene sulfonic acid-induced colitis. Fundam Clin Pharmacol. 2013;27(3):299–307.
  • Omodho B, Miao T, Symonds ALJ, et al. Transcription factors early growth response gene (Egr) 2 and 3 control inflammatory responses of tolerant T cells. Immun Inflamm Dis. 2018;6(2):221–233.
  • Thomson AW, Geller DA, Gandhi C, et al. Hepatic antigen-presenting cells and regulation of liver transplant outcome. Immunol Res. 2011;50(2–3):221–227.
  • Hassan SB, Sørensen JF, Olsen BN, et al. Anti-CD40-mediated cancer immunotherapy: an update of recent and ongoing clinical trials. Immunopharmacol Immunotoxicol. 2014;36(2):96–104.
  • Lazaro E, Caubet O, Menard F, et al. Large granular lymphocyte leukemia. Presse Med. 2007;36(11 Pt 2):1694–1700.
  • Mizuiri S, Iwamoto M, Miyagi M, et al. Activation of nuclear factor-kappa B and macrophage invasion in cyclosporin A-and tacrolimus-treated renal transplants. Clin Transplant. 2004;18(1):14–20.
  • Srinivas NR. Pharmacology of pimasertib, a selective MEK1/2 inhibitor. Eur J Drug Metab Pharmacokinet. 2018;43(4):373–382.
  • Wang Y, Tang Q, Duan P, et al. Curcumin as a therapeutic agent for blocking NF-κB activation in ulcerative colitis. Immunopharmacol Immunotoxicol. 2018;40(6):476–482.
  • Kaul D, Sasikala M, Raina A. Regulatory role of miR-2909 in cell-mediated immune response. Cell Biochem Funct. 2012;30(6):500–504.
  • Wang N, Liang S, Jin J, et al. CD226 attenuates Treg suppressive capacity via CTLA-4 and TIGIT during EAE. Immunol Res. 2019;67(6):486–496.
  • Ahmad SH, Smith R, Camilleri B. Belatacept, kidney transplantation and COVID-19: successful management of the first reported case within the United Kingdom. Clin Transplant. 2020;34(9):e14026.
  • Vanhove B, Soulillou JP. Technology evaluation: Belatacept, Bristol-Myers squibb. Curr Opin Mol Ther. 2005;7(4):384–393.
  • Leichner TM, Satake A, Kambayashi T. TCR signaling by conventional CD4+ T cells is required for optimal maintenance of peripheral regulatory T cell numbers. Immun Inflamm Dis. 2016;4(2):148–154.
  • Ge Z, Wu S, Zhang Z, et al. Mechanism of tumor cells escaping from immune surveillance of NK cells. Immunopharmacol Immunotoxicol. 2020;42(3):187–198.
  • Ensor CR, Goehring KC, Iasella CJ, et al. Belatacept for maintenance immunosuppression in cardiothoracic transplantation: the potential frontier. Clin Transplant. 2018;32(10):e13363.
  • Snanoudj R, Frangie C, Deroure B, et al. The blockade of T-cell co-stimulation as a therapeutic stratagem for immunosuppression: focus on belatacept. Biol-Targets Ther. 2007;1(3):203–213.
  • Vincenti F, Larsen C, Durrbach A, Belatacept Study Group, et al. Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005;353(8):770–781.
  • Altmeyer MD, Kerisit KG, Boh EE. Therapeutic hotline. Abatacept: our experience of use in two patients with refractory psoriasis and psoriatic arthritis. Dermatol Ther. 2011;24(2):287–290.
  • Heninger AK, Wentrup S, Al-Saeedi M, et al. Immunomodulation of human intestinal T cells by the synthetic CD80 antagonist RhuDex®. Immun Inflamm Dis. 2014;2(3):166–180.
  • Biancone L. Belatacept: new prospects related to immunosuppression. G Ital Nefrol. 2007;24(5):365.
  • Azuma H, Chandraker A, Nadeau K, et al. Blockade of T-cell costimulation prevents development of experimental chronic renal allograft rejection. Proc Natl Acad Sci U S A. 1996;93(22):12439–12444.
  • 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.
  • Florman S, Vincenti F, Durrbach A, et al. Outcomes at 7 years post-transplant in black vs nonblack kidney transplant recipients administered belatacept or cyclosporine in BENEFIT and BENEFIT-EXT. Clin Transplant. 2018;32(4):e13225.
  • Grinyo J, Alberu J, Contieri FL, et al. Improvement in renal function in kidney transplant recipients switched from cyclosporine or tacrolimus to belatacept: 2-year results from the long-term extension of a phase II study. Transplant Int. 2012;25(10):1059–1064.
  • 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.
  • Bassil N, Rostaing L, Mengelle C, et al. Prospective monitoring of cytomegalovirus, Epstein-Barr virus, BK virus, and JC virus infections on belatacept therapy after a kidney transplant. Exp Clin Transplant. 2014;12(3):212–219.
  • Selmi C, Generali E, Massarotti M, et al. New treatments for inflammatory rheumatic disease. Immunol Res. 2014;60(2–3):277–288.
  • Khan WN, Wright JA, Kleiman E, et al. B-lymphocyte tolerance and effector function in immunity and autoimmunity. Immunol Res. 2013;57(1–3):335–353.
  • Willen D, Uhl W, Wolna P, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of atacicept in a randomized trial in healthy Caucasian and Japanese subjects. Eur J Drug Metab Pharmacokinet. 2020;45(1):27–40.
  • Gottenberg JE, Lorenzo N, Sordet C, et al. When biologics should be used in systemic lupus erythematosus? Presse Med. 2014;43(6 Pt 2):e181–e185.
  • Ding C. Belimumab, an anti-BLyS human monoclonal antibody for potential treatment of inflammatory autoimmune diseases. Expert Opin Biol Ther. 2008;8(11):1805–1814.
  • Wallace DJ, Navarra S, Petri MA, BLISS-52 and -76, and LBSL02 Study Groups, et al. Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus. Lupus. 2013;22(2):144–154.
  • Amoura Z, Piette JC. New therapeutic approaches to autoimmune diseases. Presse Med. 2006;35(4):709–713.
  • Baker KP, Edwards BM, Main SH, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum. 2003;48(11):3253–3265.
  • 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(10):2754–2762.
  • Zachary AA, Kopchaliiska D, Jackson AM, et al. Immunogenetics and immunology in transplantation. Immunol Res. 2010;47(1–3):232–239.
  • Engür S, Dikmen M, Öztürk Y. Comparison of antiproliferative and apoptotic effects of a novel proteasome inhibitor MLN2238 with bortezomib on K562 chronic myeloid leukemia cells. Immunopharmacol Immunotoxicol. 2016;38(2):87–97.
  • Chen D, Frezza M, Schmitt S, et al. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets. 2011;11(3):239–253.
  • Perry DK, Burns JM, Pollinger HS, et al. Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. Am J Transplant. 2009;9(1):201–209.
  • San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359(9):906–917.
  • Reece DE, Sullivan D, Lonial S, et al. Pharmacokinetic and pharmacodynamic study of two doses of bortezomib in patients with relapsed multiple myeloma. Cancer Chemother Pharmacol. 2011;67(1):57–67.
  • Venkatakrishnan K, Rader M, Ramanathan RK, et al. Effect of the CYP3A inhibitor ketoconazole on the pharmacokinetics and pharmacodynamics of bortezomib in patients with advanced solid tumors: a prospective, multicenter, open-label, randomized, two-way crossover drug-drug interaction study. Clin Ther. 2009; 31 Pt 2:2444–2458.
  • Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348(26):2609–2617.
  • Pour L, Adam Z, Buresova L, et al. Varicella-zoster virus prophylaxis with low-dose acyclovir in patients with multiple myeloma treated with bortezomib. Clin Lymphoma Myeloma. 2009;9(2):151–153.
  • Dennis M, Maoz A, Hughes D, et al. Bortezomib ocular toxicities: outcomes with ketotifen. Am J Hematol. 2019;94(3):E80–E82.
  • Ingvar A, Smedby KE, Lindelof B, et al. Immunosuppressive treatment after solid organ transplantation and risk of post-transplant cutaneous squamous cell carcinoma. Nephrol Dial Transplant. 2010;25(8):2764–2771.
  • Curran MP, McKeage K. Bortezomib: a review of its use in patients with multiple myeloma. Drugs. 2009;69(7):859–888.
  • Holt CD. Overview of immunosuppressive therapy in solid organ transplantation. Anesthesiol Clin. 2017;35(3):365–380.
  • Khan ML, Stewart A. Carfilzomib: a novel second-generation proteasome inhibitor. Future Oncol. 2011;7(5):607–612.
  • Tremblay S, Driscoll JJ, Rike ‐Shields A, et al. A prospective, iterative, adaptive trial of carfilzomib-based desensitization. Am J Transplant. 2020;20(2):411–421.
  • Ensor C, Yousem S, Marrari M, et al. Proteasome inhibitor carfilzomib‐based therapy for antibody‐mediated rejection of the pulmonary allograft: use and short‐term findings. Am J Transplant. 2017;17(5):1380–1388.
  • Yuan N, Yu G, Liu D, et al. An emerging role of interleukin-23 in rheumatoid arthritis. Immunopharmacol Immunotoxicol. 2019;41(2):185–191.
  • Khabbazi S, Jacques RO, Moyano Cardaba C, et al. Janus kinase 2 and signal transducer and activator of transcription 3 activation is not essential for CCL3-, CCL5- or CCL8-induced chemotaxis. Cell Biochem Funct. 2013;31(4):312–318.
  • Schwartz DM, Kanno Y, Villarino A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;17(1):78–862.
  • Borie DC, O'Shea JJ, Changelian PS. JAK3 inhibition, a viable new modality of immunosuppression for solid organ transplants. Trends Mol Med. 2004;10(11):532–541.
  • Changelian PS, Flanagan ME, Ball DJ, et al. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science. 2003;302(5646):875–878.
  • Chang ZY, Sun R, Ma YS, et al. Differential gene expression of the key signalling pathway in Para-carcinoma, carcinoma and relapse human pancreatic cancer. Cell Biochem Funct. 2014;32(3):258–267.
  • Hvas CL, Bendix M, Dige A, et al. Current, experimental, and future treatments in inflammatory bowel disease: a clinical review. Immunopharmacol Immunotoxicol. 2018;40(6):446–460.
  • Zand MS. Tofacitinab in renal transplantation. Transplant Rev (Orlando). 2013;27(3):85–89.
  • Kontzias A, Kotlyar A, Laurence A, et al. Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease. Curr Opin Pharmacol. 2012;12(4):464–470.
  • Fiocco U, Accordi B, Martini V, et al. JAK/STAT/PKCδ molecular pathways in synovial fluid T lymphocytes reflect the in vivo T helper-17 expansion in psoriatic arthritis. Immunol Res. 2014;58(1):61–69.
  • Ghoreschi K, Jesson MI, Li XO, et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol. 2011;186(7):4234–4243.
  • Winthrop KL, Curtis JR, Lindsey S, et al. Herpes zoster and tofacitinib: clinical outcomes and the risk of concomitant therapy. Arthritis Rheumatol. 2017;69(10):1960–1968.
  • Higuchi T, Shiraishi T, Shirakusa T, et al. Prevention of acute lung allograft rejection in rat by the janus kinase 3 inhibitor, tyrphostin AG490. J Heart Lung Transplant. 2005;24(10):1557–1564.
  • Deuse T, Hua X, Taylor V, et al. Significant reduction of acute cardiac allograft rejection by selective janus kinase-1/3 inhibition using R507 and R545. Transplantation. 2012;94(7):695–702.
  • Rousvoal G, Si MS, Lau M, et al. Janus kinase 3 inhibition with CP-690,550 prevents allograft vasculopathy. Transplant Int. 2006;19(12):1014–1021.
  • Thoma G, Drückes P, Zerwes H-G. Selective inhibitors of the Janus kinase Jak3-are they effective? Bioorg Med Chem Lett. 2014;24(19):4617–4621.
  • Wojciechowski D, Vincenti F. Tofacitinib in kidney transplantation. Expert Opin Investig Drugs. 2013;22(9):1193–1199.
  • Harada T, Nakamura H. Pharmacology profile and clinical findings of tofacitinib citrate (Xeljanz® tablet 5 mg). Nihon Yakurigaku Zasshi. 2014;144(3):133–141.
  • 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.
  • Ostojic A, Vrhovac R, Verstovsek S. Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol. 2011;7(9):1035–1043.
  • Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787–798.
  • Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807.
  • Santos FP, Verstovsek S. Efficacy of ruxolitinib for myelofibrosis. Expert Opin Pharmacother. 2014;15(10):1465–1473.
  • Yang LP, Keating GM. Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012;72(16):2117–2127.
  • Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426–435.
  • Hobbs G, Rampal R. JAK2 mutations and JAK inhibitors in the management of myeloproliferative neoplasms. Contemp Oncol. 2015;7:22–28.
  • Barnett AN, Asgari E, Chowdhury P, et al. The use of eculizumab in renal transplantation. Clin Transplant. 2013;27(3):E216–E229.
  • Coppo P. Thrombotic microangiopathies: from empiricism to targeted therapies. Presse Med. 2012;41(3 Pt 2):e101–e104.
  • Thomson N, Ulrickson M. Maintenance eculizumab dose adjustment in the treatment of atypical hemolytic uremic syndrome: a case report and review of the literature. Clin Case Rep. 2016;4(8):773–776.
  • Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008;111(4):1840–1847.
  • Gonzalez-Roncero F, Suner M, Bernal G, et al. Eculizumab treatment of acute antibody-mediated rejection in renal transplantation: case reports. Transplant Proc. 2012;44(9):2690–2694.
  • Stewart Z, Collins T, Schlueter A, et al. Case report: eculizumab rescue of severe accelerated antibody-mediated rejection after ABO-incompatible kidney transplant. Transplant Proc. 2012;44(10):3033–3036.
  • Zeevi A, Girnita A, Duquesnoy R. HLA antibody analysis: sensitivity, specificity, and clinical significance in solid organ transplantation. Immunol Res. 2006;36(1–3):255–264.
  • Kaya Aksoy G, Comak E, Koyun M, et al. Tacrolimus variability: a cause of donor-specific anti-HLA antibody formation in children. Eur J Drug Metab Pharmacokinet. 2019;44(4):539–548.
  • Orandi BJ, Zachary AA, Dagher NN, et al. Eculizumab and splenectomy as salvage therapy for severe antibody-mediated rejection after HLA-incompatible kidney transplantation. Transplantation. 2014;98(8):857–863.
  • Stegall MD, Diwan T, Raghavaiah S, et al. Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients. Am J Transplant. 2011;11(11):2405–2413.
  • Kulkarni S, Kirkiles-Smith NC, Deng YH, et al. Eculizumab therapy for chronic antibody-mediated injury in kidney transplant recipients: a pilot randomized controlled trial. Am J Transplant. 2017;17(3):682–691.
  • Yeung MY, Gabardi S, Sayegh MH. Use of polyclonal/monoclonal antibody therapies in transplantation. Expert Opin Biol Ther. 2017;17(3):339–352.
  • Iliopoulou BP, Huber BT. Emergence of chronic lyme arthritis: putting the breaks on CD28 costimulation. Immunopharmacol Immunotoxicol. 2009;31(2):180–185.
  • Kurlberg G, Haglind E, Schon K, et al. Blockade of the B7-CD28 pathway by CTLA4-Ig counteracts rejection and prolongs survival in small bowel transplantation. Scand J Immunol. 2000;51(3):224–230.
  • Liu D, Krummey SM, Badell IR, et al. 2B4 (CD244) induced by selective CD28 blockade functionally regulates allograft-specific CD8+ T cell responses. J Exp Med. 2014;211(2):297–311.
  • Shi R, Honczarenko M, Zhang S, et al. Pharmacokinetic, pharmacodynamic, and safety profile of a novel anti-CD28 domain antibody antagonist in healthy subjects. J Clin Pharmacol. 2017;57(2):161–172.
  • Poirier N, Blancho G, Hiance M, et al. First-in-human study in healthy subjects with FR104, a pegylated monoclonal antibody fragment antagonist of CD28. J Immunol. 2016;197(12):4593–4602.
  • Adams AB, Ford ML, Larsen CP. Costimulation blockade in autoimmunity and transplantation: the CD28 pathway. J Immunol. 2016;197(6):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(1):88–100.
  • Ville S, Poirier N, Branchereau J, et al. Anti-CD28 antibody and belatacept exert differential effects on mechanisms of renal allograft rejection. J Am Soc Nephrol. 2016;27(12):3577–3588.
  • Suchard SJ, Davis PM, Kansal S, et al. A monovalent anti-human CD28 domain antibody antagonist: preclinical efficacy and safety. J Immunol. 2013;191(9):4599–4610.
  • Sellberg F, Berglund D, Binder C, et al. Pharmacokinetic and pharmacodynamic study of a clinically effective anti-CD2 monoclonal antibody. Scand J Immunol. 2020;91(1):e12839.
  • Van Der Merwe PA, Barclay AN, Mason DW, et al. Human cell-adhesion molecule CD2 binds CD58 (LFA-3) with a very low affinity and an extremely fast dissociation rate but does not bind CD48 or CD59. Biochemistry. 1994;33(33):10149–10160.
  • Suthanthiran M, editor. Signaling via the T-cell antigen receptor heterodimer and the CD2 antigen: a novel, synergistic pathway for activation of T-cells. Transplant Proc. 1989:21(1 Pt 1): 340–341.
  • Kapur S, Khanna A, Sharma VK, et al. CD2 antigen targeting reduces intragraft expression of mRNA-encoding granzyme B and IL-10 and induces tolerance. Transplantation. 1996;62(2):249–255.
  • Przepiorka D, Phillips GL, Ratanatharathorn V, et al. A phase II study of BTI-322, a monoclonal anti-CD2 antibody, for treatment of steroid-resistant acute graft-versus-host disease. Blood. 1998;92(11):4066–4071.
  • Kawai T, Cosimi AB, Spitzer TR, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008;358(4):353–361.
  • Larsen CP, Pearson TC. The CD40 pathway in allograft rejection, acceptance, and tolerance. Curr Opin Immunol. 1997;9(5):641–647.
  • Mohammadi A, Mehrzad J, Mahmoudi M, et al. Effect of culture and maturation on human monocyte-derived dendritic cell surface markers, necrosis and antigen binding. Biotech Histochem. 2015;90(6):445–452.
  • Das ND, Jung KH, Choi MR, et al. Gene networking and inflammatory pathway analysis in a JMJD3 knockdown human monocytic cell line. Cell Biochem Funct. 2012;30(3):224–232.
  • Yang B, Tan X, Xiong X, et al. Effect of CD40/CD40L signaling on IL-10-producing regulatory B cells in Chinese children with Henoch-Schönlein purpura nephritis. Immunol Res. 2017;65(3):592–604.
  • Notarangelo LD, Peitsch MC, Abrahamsen TG, et al. CD40lbase: a database of CD40L gene mutations causing X-linked hyper-IgM syndrome. Immunol Today. 1996;17(11):511–516.
  • Legany N, Berta L, Kovacs L, et al. The role of B7 family costimulatory molecules and indoleamine 2,3-dioxygenase in primary Sjögren's syndrome and systemic sclerosis. Immunol Res. 2017;65(3):622–629.
  • Esposito P, Grosjean F, Rampino T, et al. Costimulatory pathways in kidney transplantation: pathogenetic role, clinical significance and new therapeutic opportunities. Int Rev Immunol. 2014;33(3):212–233.
  • Vincenti F, Yang H, Klintmalm G, et al. Clinical outcomes in a phase 1b, randomized, double-blind, parallel group, placebo-controlled, single-dose study of ASKP1240 in de novo kidney transplantation.: abstract# 181. Am J Transplant. 2013;13.
  • Oura T, Yamashita K, Suzuki T, et al. Long-term hepatic allograft acceptance based on CD40 blockade by ASKP1240 in nonhuman primates. Am J Transplant. 2012;12(7):1740–1754.
  • Cordoba F, Wieczorek G, Audet M, et al. A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion. Am J Transplant. 2015;15(11):2825–2836.
  • Ulrich P, Flandre T, Espie P, et al. Nonclinical safety assessment of CFZ533, a Fc-silent anti-CD40 antibody, in cynomolgus monkeys. Toxicol Sci. 2018;166(1):192–202.
  • Ristov J, Espie P, Ulrich P, et al. Characterization of the in vitro and in vivo properties of CFZ533, a blocking and non-depleting anti-CD40 monoclonal antibody . Am J Transplant. 2018;18(12):2895–2904.
  • Nashan B, Tedesco H, Van Den Hoogen M, et al. CFZ533, a new anti-CD40 mAB demonstrates comparable efficacy and better renal function versus tacrolimus in de-novo CNI-free kidney transplantation. Am J Transplant. 2018;18:400.
  • Yalcin AD, Yalcin AN. Future perspective: biologic agents in patients with severe COVID-19. Immunopharmacol Immunotoxicol. 2021;43(1):1–7.
  • Wang XF, van Velkinburgh JC, Zhang Y, et al. Effects of immunosuppressive agents on Th17 cells involved in transplantation. Clin Transplant. 2013;27(1):E12–E20.
  • Genovese MC, McKay JD, Nasonov EL, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 2008;58(10):2968–2980.
  • Choi J, Aubert O, Vo A, et al. Assessment of tocilizumab (anti-interleukin-6 receptor monoclonal) as a potential treatment for chronic antibody-mediated rejection and transplant glomerulopathy in HLA-sensitized renal allograft recipients. Am J Transplant. 2017;17(9):2381–2389.
  • Abel M, Aspeslet L, Freitag D. ISATX247: a novel calcineurin inhibitor with minimal renal toxicity. Am J Transplant. 2001;1(Suppl 1): 161.
  • ISA 247: trans-ISA 247, trans-R 1524, ISA(TX)247, ISAtx 247, ISATx247, LX 211, LX211, R 1524, R-1524. Drugs R D. 2007. 8(2):103–112.
  • Bîrsan T, Dambrin C, Freitag DG, et al. The novel calcineurin inhibitor ISA247: a more potent immunosuppressant than cyclosporine in vitro. Transplant Int. 2004;17(12):767–771.
  • Busque S, Cantarovich M, Mulgaonkar S, PROMISE Investigators, 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.
  • Schultz C. Voclosporin as a treatment for noninfectious uveitis. Ophthalmol Eye Dis. 2013;5:5–10.
  • Blasco H, Chatelut E, de Bretagne IB, et al. Pharmacokinetics of rituximab associated with CHOP chemotherapy in B-cell non-Hodgkin lymphoma. Fundam Clin Pharmacol. 2009;23(5):601–608.
  • De Virgilio A, de Vincentiis M, Inghilleri M, et al. Idiopathic hypertrophic pachymeningitis: an autoimmune IgG4-related disease. Immunol Res. 2017;65(1):386–394.
  • Raffray L, Guillevin L. Updates for the treatment of EGPA. Presse Med. 2020;49(3):104036.
  • Bachelet T, Visentin J, Davis P, et al. The incidence of post-transplant malignancies in kidney transplant recipients treated with rituximab. Clin Transplant. 2021;35(2):e14171.
  • Lapointe R, Bellemare-Pelletier A, Housseau F, et al. CD40-stimulated B lymphocytes pulsed with tumor antigens are effective antigen-presenting cells that can generate specific T cells. Cancer Res. 2003;63(11):2836–2843.
  • Hoffman W, Lakkis FG, Chalasani G. B cells, antibodies, and more. Clin J Am Soc Nephrol. 2016;11(1):137–154.
  • Cherukuri A, Rothstein DM, Clark B, et al. Immunologic human renal allograft injury associates with an altered IL-10/TNF-α expression ratio in regulatory B cells . J Am Soc Nephrol. 2014;25(7):1575–1585.
  • Taylor RP, Lindorfer MA. Drug insight: the mechanism of action of rituximab in autoimmune disease – the immune complex decoy hypothesis. Nat Clin Pract Rheumatol. 2007;3(2):86–95.
  • Genberg H, Hansson A, Wernerson A, et al. Pharmacodynamics of rituximab in kidney allotransplantation. Am J Transplant. 2006;6(10):2418–2428.
  • Salar A, Avivi I, Larouche J-F, et al. Final results of the BP22333 study demonstrate non-inferior pharmacokinetics (PK) and safety of subcutaneous (SC) administration of rituximab compared with intravenous (IV) administration as maintenance therapy in patients with follicular lymphoma (FL). Am Soc Hematol. 2012;120:1641.
  • Muller C, Murawski N, Wiesen MH, et al. The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood. 2012;119(14):3276–3284.
  • Patel J, Ho M, Ho V, et al. Rapid infusion rituximab for maintenance therapy: is it feasible? Leuk Res Treatment. 2013;2013:629283.
  • Kamar N, Milioto O, Puissant-Lubrano B, et al. Incidence and predictive factors for infectious disease after rituximab therapy in kidney-transplant patients. Am J Transplant. 2010;10(1):89–98.
  • Grim SA, Pham T, Thielke J, et al. Infectious complications associated with the use of rituximab for ABO-incompatible and positive cross-match renal transplant recipients. Clin Transplant. 2007;21(5):628–632.
  • Faguer S, Kamar N, Guilbeaud-Frugier C, et al. Rituximab therapy for acute humoral rejection after kidney transplantation. Transplantation. 2007;83(9):1277–1280.
  • Lefaucheur C, Nochy D, Andrade J, et al. Comparison of combination plasmapheresis/IVIg/anti-CD20 versus high-dose IVIg in the treatment of antibody-mediated rejection. Am J Transplant. 2009;9(5):1099–1107.
  • Kaposztas Z, Podder H, Mauiyyedi S, et al. Impact of rituximab therapy for treatment of acute humoral rejection. Clin Transplant. 2009;23(1):63–73.
  • 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(2):391–399.
  • Shiu KY, Stringer D, McLaughlin L, et al. Effect of optimized immunosuppression (including rituximab) on anti-donor alloresponses in patients with chronically rejecting renal allografts. Front Immunol. 2020;11:79.
  • Reddy V, Klein C, Isenberg DA, et al. Obinutuzumab induces superior B-cell cytotoxicity to rituximab in rheumatoid arthritis and systemic lupus erythematosus patient samples. Rheumatology (Oxford). 2017;56(7):1227–1237.
  • Jordan SC, Ammerman N, Choi J, et al. Novel therapeutic approaches to allosensitization and antibody-mediated rejection. Transplantation. 2019;103(2):262–272.
  • Mössner E, Brünker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010;115(22):4393–4402.
  • Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101–1110.
  • Redfield RR, Jordan SC, Busque S, et al. Safety, pharmacokinetics, and pharmacodynamic activity of obinutuzumab, a type 2 anti-CD20 monoclonal antibody for the desensitization of candidates for renal transplant. Am J Transplant. 2019;19(11):3035–3045.
  • Choi J, Vo A, Huang E, et al. Experience with obinutuzumab (Type II anti-CD20) in kidney transplant patients with donor specific antibody (DSA plus) antibody mediated rejection. 2017 American Transplant Congress. Abstract # 293.
  • Parlakpinar H, Tasdemir S, Polat A, et al. Protective effect of chelerythrine on gentamicin-induced nephrotoxicity. Cell Biochem Funct. 2006;24(1):41–48.
  • Yanashima K, Chieosilapatham P, Yoshimoto E, et al. Innate defense regulator IDR-1018 activates human mast cells through G protein-, phospholipase C-, MAPK- and NF-ĸB-sensitive pathways. Immunol Res. 2017;65(4):920–931.
  • Sommerer C, Zeier M. AEB071 – a promising immunosuppressive agent. Clin Transplant. 2009;23(Suppl 21):15–18.
  • Matz M, Naik M, Mashreghi MF, et al. Evaluation of the novel protein kinase C inhibitor sotrastaurin as immunosuppressive therapy after renal transplantation. Expert Opin Drug Metab Toxicol. 2011;7(1):103–113.
  • Spitaler M, Cantrell DA. Protein kinase C and beyond. Nat Immunol. 2004;5(8):785–790.
  • Guo B, Su TT, Rawlings DJ. Protein kinase C family functions in B-cell activation. Curr Opin Immunol. 2004;16(3):367–373.
  • Bigaud M, Wieczorek G, Riesen S, et al. Nvp-Aeb071 (aeb), a novel oral inhibitor of early T-Cell activation, prolongs the survival of non-human primate (nhp) kidney allografts when used as monotherapy or at non-effective doses combined with a non-effective dose of cyclosporine (csa). Transplantation. 2006;82(1):250.
  • Friman S, Arns W, Nashan B, et al. Sotrastaurin, a novel small molecule inhibiting protein-kinase C: randomized phase II study in renal transplant recipients. Am J Transplant. 2011;11(7):1444–1455.
  • Tedesco ‐Silva H, Kho M, 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.
  • Skvara H, Dawid M, Kleyn E, et al. The PKC inhibitor AEB071 may be a therapeutic option for psoriasis. J Clin Invest. 2008;118(9):3151–3159.
  • Sanders ML, Langone A, Management R. Drugs in development for prophylaxis of rejection in kidney-transplant recipients. Transplant Res Risk Manag. 2015;7:59–69.
  • Zhang W, Egashira N. Masuda S. Recent topics on the mechanisms of immunosuppressive therapy-related neurotoxicities. Int J Mol Sci. 2019;20(13):3210.
  • Stephen DM. New immunosuppressants in pediatric solid organ transplantation. Curr Opin Organ Transplant. 2012;17(5):503–508.
  • Enderby C, Keller C. An overview of immunosuppression in solid organ transplantation. Am J Manag Care. 2015;21(1 Suppl):S12–S23.
  • White SL, Hirth R, Mahillo B, et al. The global diffusion of organ transplantation: trends, drivers and policy implications. Bull World Health Organ. 2014;92(11):826–835.

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