Immunology and Biotherapies

KeywordsAdverse reactions; Cytokines; Monoclonal antibodies; Bone morphogenic proteins;Colony-stimulating factors; Interferons; Interleukins; Tumor necrosis factor alfa;Adalimumab; Certolizumab; Etanercept; Golimumab; Infliximab; Abciximab;Alemtuzumab; Bevacizumab; Cetuximab; Daclizumab; Natalizumab; Ranibizumab;Rituximab; Tocilizumab; Trastuzumab

Via Krishan Maggon

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 8mg/kg. Up to 8mg/kg of daclizumab administered every 3weeks 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.

 

Highlights

 

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Interleukin-2 receptor alpha chain (CD25) is overexpressed by ATL leukemia cells.

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Daclizumab a humanized monoclonal antibody blocks IL-2 binding to CD25.

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8 mg/kg of daclizumab is required to get ≥ 95% saturation of CD25 in lymph nodes.

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Partial responses were observed in patients with chronic and smoldering ATL.

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The study provides a rationale for high-dose treatment in lymphoid malignancies.

 

Via Krishan Maggon