Submitted April 4, 2008
Accepted October 9, 2008
Effective treatment of a murine model of adult T-cell leukemia using depsipeptide and its combination with unmodified daclizumab directed toward CD25
Jing Chen, Meili Zhang, Wei Ju, and Thomas A Waldmann*
Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States
* Corresponding author; email: tawald{at}helix.nih.gov.
Adult T-cell leukemia (ATL) is caused by human T-cell lymphotropic virus I (HTLV-1) and is an aggressive malignancy of CD4, CD25 expressing leukemia and lymphoma cells. There is no accepted curative therapy for ATL. Depsipeptide, a histone deacetylase inhibitor, has demonstrated major anti-tumor effects in leukemias and lymphomas. In this study, we investigated the therapeutic efficacy of depsipeptide alone and in combination with daclizumab (HAT, humanized anti-Tac) in a murine model of human ATL. The Met-1 ATL model was established by intraperitoneal injection of ex vivo leukemic cells into NOD/SCID mice. Either depsipeptide, given at 0.5mg/kg every other day for 2 weeks, or daclizumab, given at 100ug weekly for 4 weeks, inhibited tumor growth as monitored by serum levels of soluble IL-2R
(sIL-2R) and soluble 
2-microglobulin(2µ) (P<0.0001), and prolonged survival of the leukemia-bearing mice (P<0.0001) as compared with the control group. Combination of depsipeptide with daclizumab dramatically enhanced the anti-tumor effect, as shown by both sIL-2R and 2µ levels and survival of the leukemia-bearing mice, when compared with those in the depsipeptide or daclizumab alone groups (P<0.001). The significantly improved therapeutic efficacy by combining depsipeptide with daclizumab supports a clinical trial of this combination in the treatment of ATL.
