Inhibition of acute graft-versus-host disease with retention of graft-versus-tumor effects by the proteasome inhibitor bortezomib. Academic Article uri icon


  • Graft-versus-host disease (GVHD) represents a major hurdle impeding the efficacy of allogeneic bone marrow transplantation (BMT). Bortezomib is a proteasome inhibitor that was recently approved for treatment of myeloma. We found that bortezomib potently inhibited in vitro mixed lymphocyte responses and promoted the apoptosis of alloreactive T cells. Bortezomib given at the time of allogeneic BMT in mice resulted in significant protection from acute GVHD. Reductions in GVHD-associated parameters and biological evidence of proteasome inhibition were observed with this regimen but with no adverse effects on long-term donor reconstitution. Assessment of graft-versus-tumor responses in advanced leukemia-bearing mice demonstrated that only the combination of allogeneic BMT and T cells with bortezomib promoted significant increases in survival. Increased cytotoxic T cell killing of the tumor was also observed. Thus, the combination of proteasome inhibition with selective immune attack can markedly increase the efficacy of BMT in cancer.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 6

author list (cited authors)

  • Sun, K., Welniak, L. A., Panoskaltsis-Mortari, A., O'Shaughnessy, M. J., Liu, H., Barao, I., ... Murphy, W. J.

citation count

  • 218

complete list of authors

  • Sun, Kai||Welniak, Lisbeth A||Panoskaltsis-Mortari, Angela||O'Shaughnessy, Matthew J||Liu, Haiyan||Barao, Isabel||Riordan, William||Sitcheran, Raquel||Wysocki, Christian||Serody, Jonathan S||Blazar, Bruce R||Sayers, Thomas J||Murphy, William J

publication date

  • May 2004