Proteasome Inhibitors as Immunosuppressants: Biological Rationale and Clinical Experience

Eva Moran, Federico Carbone, Valeria Augusti, Franco Patrone, Alberto Ballestrero, Alessio Nencioni

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)270-276
Number of pages7
JournalSeminars in Hematology
Volume49
Issue number3
DOIs
Publication statusPublished - Jul 2012

ASJC Scopus subject areas

  • Hematology

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