کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3256859 | 1207366 | 2014 | 12 صفحه PDF | دانلود رایگان |
• Interleukin-2 receptor alpha chain (CD25) is overexpressed by ATL leukemia cells.
• Daclizumab a humanized monoclonal antibody blocks IL-2 binding to CD25.
• 8 mg/kg of daclizumab is required to get ≥ 95% saturation of CD25 in lymph nodes.
• Partial responses were observed in patients with chronic and smoldering ATL.
• The study provides a rationale for high-dose treatment in lymphoid malignancies.
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.
Journal: Clinical Immunology - Volume 155, Issue 2, December 2014, Pages 176–187