Antileukemic effect of daclizumab in CD25 high-expressing leukemias and impact of tumor burden on antibody dosing

Koon, H.B.; Severy, P.; Hagg, D.S.; Butler, K.; Hill, T.; Jones, A.G.; Waldmann, T.A.; Junghans, R.P.

doi:10.1016/j.leukres.2005.06.007

« Previous Next »Leukemia Research
Volume 30, Issue 2 , Pages 190-203, February 2006

Antileukemic effect of daclizumab in CD25 high-expressing leukemias and impact of tumor burden on antibody dosing

H.B. Koon
- Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
P. Severy
- Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
D.S. Hagg
- Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
K. Butler
- Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
T. Hill
- Division of Nuclear Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
A.G. Jones
- Division of Nuclear Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
T.A. Waldmann
- Metabolism Branch, National Cancer Institute, National Institutes of Heath, Bethesda, MD, USA
R.P. Junghans
- Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Corresponding author. Present address: Department of Surgery, Roger Williams Medical Center, 825 Chalkstone Avenue, Providence, RI 02908, USA. Tel.: +1 401 456 2507; fax: +1 401 456 4812.

Received 11 March 2005; accepted 16 June 2005. published online 07 March 2011.

Abstract

Humanized anti-CD25 antibody, daclizumab, was applied in a pilot study of 10 patients with CD25(+) leukemias and pharmacokinetic/pharmacodynamic properties were characterized. Two widely held concepts – tumor sink accelerating pharmacokinetics and higher antigen expression correlating with target cell clearance – were supported by this first systematic evaluation of these questions with actual human clinical data. A flexi-dosing regimen was validated for maintaining target drug levels in vivo with a wide range of tumor burdens. Daclizumab induced clearance of peripheral leukemic cells when highly positive for CD25, but durable responses were not obtained. If daclizumab will have a role in antileukemic therapy, it may be in minimal disease settings or as a component of a combination regimen, but only when CD25 expression is high.

Abbreviations: ADCC, antibody-dependent cellular cytotoxicity, ALL, acute lymphocytic leukemia, AML, acute myleogenous leukemia, CLL, chronic lymphocytic leukemia, CML, chronic myleogenous leukemia, HAHA, human anti-humanized antibody, HAMA, human anti-mouse antibody, HAT, humanized anti-Tac, MAT, murine anti-Tac, MFI, mean fluorescence intensity, MMPS, monocyte–macrophage phagocytic system (reticuloendothelial system), PE, phycoerythrin, Tac, T-cell activation antigen (CD25)