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Clin Immunol. 2014 Dec;155(2):176-87. doi: 10.1016/j.clim.2014.09.012. Epub 2014 Sep 28.

Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma.

Author information

1
Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
3
Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
4
Clinical Pathology Department, National Institutes of Health, Bethesda, MD 20892, USA.
5
Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
6
Department of Haematology and Pathology, University of the West Indies, Kingston, Jamaica.
7
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
8
Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: tawald@helix.nih.gov.

Abstract

Interleukin-2 receptor α chain (CD25) is overexpressed in human T-cell leukemia virus 1 associated adult T-cell leukemia/lymphoma (ATL). Daclizumab a humanized monoclonal antibody blocks IL-2 binding by recognizing the interleukin-2 receptor α chain (CD25). We conducted a phase I/II trial of daclizumab in 34 patients with ATL. Saturation of surface CD25 on circulating ATL cells was achieved at all doses; however saturation on ATL cells in lymph nodes required 8 mg/kg. Up to 8 mg/kg of daclizumab administered every 3 weeks was well tolerated. No responses were observed in 18 patients with acute or lymphoma ATL; however, 6 partial responses were observed in 16 chronic and smoldering ATL patients. The pharmacokinetics/pharmacodynamics of daclizumab suggest that high-dose daclizumab would be more effective than low-dose daclizumab in treatment of lymphoid malignancies and autoimmune diseases (e.g., multiple sclerosis) since high-dose daclizumab is required to saturate IL-2R alpha in extravascular sites.

KEYWORDS:

Adult T-cell leukemia/lymphoma; Daclizumab; Human T-cell leukemia virus 1 (HTLV-1) associated ATL; Interleukin-2 receptor alpha; Monoclonal antibody

PMID:
25267440
PMCID:
PMC4306230
DOI:
10.1016/j.clim.2014.09.012
[Indexed for MEDLINE]
Free PMC Article

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