| Autor: |
Liu, H., Murphy, W. J., Sitcheran, R., Blazar, B. R., Barao, I., Serody, J. S., Welniak, L. A., O'Shaughnessy, M. J., Riordan, W., Panoskaltsis-Mortari, A., Wysocki, C., Sun, K., Sayers, T. J. |
| Jazyk: |
angličtina |
| Rok vydání: |
2004 |
| Předmět: |
|
| DOI: |
10.17615/t2eg-ws81 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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