title: Proteasome inhibitor therapy for antibody-mediated rejection.
abstract: AMR is being recognized with increasing efficiency, but continues to present a significant threat to renal allograft survival. Traditional therapies for AMR (IVIG, plasmapheresis, rituximab, and antilymphocyte preparations) in general have provided inconsistent results and do not deplete the source of antibody production, viz., the mature plasma cell. Recently, the first plasma cell-targeted therapy in humans has been developed using bortezomib (a first in class PI) for AMR treatment in kidney transplant recipients. Initial experience with bortezomib involved treatment of refractory AMR. Subsequently, the efficacy of bortezomib in primary therapy for AMR was demonstrated. In a multicenter collaborative effort, the initial results with bortezomib in AMR have been confirmed and expanded to pediatric and adult heart transplant recipients. More recently, results from a prospective, staged desensitization trial has shown that bortezomib alone can substantially reduce anti-HLA antibody levels. These results demonstrate the significant potential of proteasome inhibition in addressing humoral barriers. However, the major advantage of proteasome inhibition lies in the numerous potential strategies for achieving synergy.
authors: Department of Surgery, University of Cincinnati, Cincinnati, OH, USA. woodlees@uc.edu
authors: E S
authors: ES
authors: Woodle
authors: R C
authors: RC
authors: Walsh
authors: R R
authors: RR
authors: Alloway
authors: A
authors: A
authors: Girnita
authors: P
authors: P
authors: Brailey
mesh_terms: D000906:Antibodies / Q000737:chemistry*; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000379:methods*; D010950:Plasma Cells / Q000166:cytology; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease