Refine
Has Fulltext
- yes (10)
Is part of the Bibliography
- yes (10)
Document Type
- Journal article (6)
- Doctoral Thesis (4)
Keywords
- leukemia (10) (remove)
Institute
- Kinderklinik und Poliklinik (3)
- Institut für Psychotherapie und Medizinische Psychologie (2)
- Medizinische Klinik und Poliklinik II (2)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (1)
- Institut für Experimentelle Biomedizin (1)
- Institut für Medizinische Strahlenkunde und Zellforschung (1)
- Institut für Virologie und Immunbiologie (1)
- Klinik für Anaesthesiologie (bis 2003) (1)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (1)
- Pathologisches Institut (1)
Hsp90 inhibition ameliorates CD4\(^{+}\) T cell-mediated acute Graft versus Host disease in mice
(2016)
Introduction:
For many patients with leukemia only allogeneic bone marrow transplantion provides a chance of cure. Co‐transplanted mature donor T cells mediate the desired Graft versus Tumor (GvT) effect required to destroy residual leukemic cells. The donor T cells very often, however, also attack healthy tissue of the patient inducing acute Graft versus Host Disease (aGvHD)—a potentially life‐threatening complication.
Methods:
Therefore, we used the well established C57BL/6 into BALB/c mouse aGvHD model to evaluate whether pharmacological inhibition of heat shock protein 90 (Hsp90) would protect the mice from aGvHD.
Results:
Treatment of the BALB/c recipient mice from day 0 to +2 after allogeneic CD4\(^{+}\) T cell transplantation with the Hsp90 inhibitor 17‐(dimethylaminoethylamino)‐17‐demethoxygeldanamycin (DMAG) partially protected the mice from aGvHD. DMAG treatment was, however, insufficient to prolong overall survival of leukemia‐bearing mice after transplantation of allogeneic CD4\(^{+}\) and CD8\(^{+}\) T cells. Ex vivo analyses and in vitro experiments revealed that DMAG primarily inhibits conventional CD4\(^{+}\) T cells with a relative resistance of CD4\(^{+}\) regulatory and CD8\(^{+}\) T cells toward Hsp90 inhibition.
Conclusions:
Our data, thus, suggest that Hsp90 inhibition might constitute a novel approach to reduce aGvHD in patients without abrogating the desired GvT effect.