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

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

Research output: Contribution to journalArticle

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)190-203
Number of pages14
JournalLeukemia Research
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2006

Keywords

  • Antibody
  • HAT
  • Humanized
  • Tac

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Koon, H. B., Severy, P., Hagg, D. S., Butler, K., Hill, T., Jones, A. G., Waldmann, T. A., & Junghans, R. P. (2006). Antileukemic effect of daclizumab in CD25 high-expressing leukemias and impact of tumor burden on antibody dosing. Leukemia Research, 30(2), 190-203. https://doi.org/10.1016/j.leukres.2005.06.007