Bortezomib for the prevention and treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

• Published in: Experimental hematology Vol. 44; no. 9; pp. 771 - 777
• Main Authors: Al-Homsi, Ahmad Samer, Feng, Yuxin, Duffner, Ulrich, Al Malki, Monzr M, Goodyke, Austin, Cole, Kelli, Muilenburg, Marlee, Abdel-Mageed, Aly
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-09-2016
• Subjects: Advanced Basic Science; Animals; Apoptosis - drug effects; Bortezomib - pharmacology; Bortezomib - therapeutic use; Clinical Trials as Topic; Cytokines - biosynthesis; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Disease Models, Animal; Graft vs Host Disease - diagnosis; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Lymphocyte Activation - drug effects; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Transplantation, Homologous; Treatment Outcome
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2016.05.005

Allogeneic hematopoietic stem cell transplantation is the standard treatment for a variety of benign and malignant conditions. However, graft-versus-host disease (GvHD) continues to present a major barrier to the success and wide applicability of this procedure. Although current GvHD prevention and treatment regimens exclusively target T cells, bortezomib, a reversible proteasome inhibitor, possesses unique immune regulatory activities that span a wide variety of cellular processes of T and dendritic cells essential for the development of GvHD. Herein, we review the current understanding of the effects of bortezomib in vitro and in animal models and summarize the clinical data relevant to its use in the prevention and treatment of GvHD. We conclude with an outline of the remaining challenges and opportunities to optimize bortezomib's potential role in this setting.