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Use of monoclonal antibodies in renal transplantation
Martijn W F van den Hoogen1, Luuk B Hilbrands
1Department of Nephrology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Monoclonal antibodies are applied in various settings in renal transplantation. Depleting T-cell antibodies are used for treatment of steroid-resistant acute rejection and as induction therapy to reduce the intensity of concomitant immunosuppressive drug therapy. Induction therapy with the nondepleting IL-2 receptor antagonists basiliximab and daclizumab, added to cyclosporine-based regimens, reduces the incidence of acute rejection without side effects. However, an increase in long-term graft and patient survival has not been demonstrated yet. The B-cell-targeting antibody rituximab is used in blood group ABO-incompatible transplantation, in desensitization protocols, and for treatment of antibody-mediated rejection. Eculizumab interrupts the complement pathway and is a promising tool for the treatment of antibody-mediated rejection and post-transplant hemolytic-uremic syndrome. Future options are monoclonal antibodies with new molecular targets and antibodies that can be used for maintenance immunosuppression in order to avoid the toxicity of existing drugs. However, in several cases, the development of new monoclonal antibodies has been hampered by safety issues.
Monoclonal antibodies are applied in various settings in renal transplantation. Depleting T-cell antibodies are used for treatment of steroid-resistant acute rejection and as induction therapy to reduce the intensity of concomitant immunosuppressive drug therapy. Induction therapy with the nondepleting IL-2 receptor antagonists basiliximab and daclizumab, added to cyclosporine-based regimens, reduces the incidence of acute rejection without side effects. However, an increase in long-term graft and patient survival has not been demonstrated yet. The B-cell-targeting antibody rituximab is used in blood group ABO-incompatible transplantation, in desensitization protocols, and for treatment of antibody-mediated rejection. Eculizumab interrupts the complement pathway and is a promising tool for the treatment of antibody-mediated rejection and post-transplant hemolytic-uremic syndrome. Future options are monoclonal antibodies with new molecular targets and antibodies that can be used for maintenance immunosuppression in order to avoid the toxicity of existing drugs. However, in several cases, the development of new monoclonal antibodies has been hampered by safety issues.
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