Proteasome inhibitors as immunosuppressants: biological rationale and clinical experience.
Accumulating evidence supports the potential of proteasome inhibitors as immunosuppressants. Proteasome inhibitors interfere with antigen processing and presentation, as well as with the signaling cascades involved in immune cell function and survival. Both myeloma and healthy plasma cells appear to be highly susceptible to proteasome inhibitors due to impaired proteasomal activity in both cell types. As a consequence, these agents can be used to reduce antibody production and thus prevent antibody-induced tissue damage. Several clinical studies have explored the potential of bortezomib, a peptide boronate proteasome inhibitor, for treating immune disorders, such as antibody-mediated organ rejection and graft-versus-host disease (GVHD), with encouraging results. Here, we discuss the biological rationale for the use of proteasome inhibitors as immunosuppressive agents and review the clinical experience with bortezomib in immune-mediated diseases.
Department of Internal Medicine, University of Genoa, Genoa, Italy.
Eva
E
Moran
Federico
F
Carbone
Valeria
V
Augusti
Franco
F
Patrone
Alberto
A
Ballestrero
Alessio
A
Nencioni
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001897:Boronic Acids / Q000276:immunology / Q000627:therapeutic use; D000069286:Bortezomib; D006084:Graft Rejection / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000276:immunology* / Q000627:therapeutic use*; D011719:Pyrazines / Q000276:immunology / Q000627:therapeutic use
D000906:Antibodies; D001897:Boronic Acids; D007166:Immunosuppressive Agents; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex