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Daclizumab: Mechanisms of Action, Therapeutic Efficacy, Adverse Events and Its Uncovering the Potential Role of Innate Immune System Recruitment as a Treatment Strategy for Relapsing Multiple Sclerosis

1
Providence Multiple Sclerosis Center, Providence Brain and Spine Institute, Portland, OR 97225, USA
2
Providence Health and Services, Regional Research Department, Portland, OR 97213, USA
*
Author to whom correspondence should be addressed.
Biomedicines 2019, 7(1), 18; https://doi.org/10.3390/biomedicines7010018
Received: 22 January 2019 / Revised: 6 March 2019 / Accepted: 6 March 2019 / Published: 11 March 2019
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis and Treatment)
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Abstract

Daclizumab (DAC) is a humanized, monoclonal antibody that blocks CD25, a critical element of the high-affinity interleukin-2 receptor (IL-2R). DAC HYP blockade of CD25 inhibits effector T cell activation, regulatory T cell expansion and survival, and activation-induced T-cell apoptosis. Because CD25 blockade reduces IL-2 consumption by effector T cells, it increases IL-2 bioavailability allowing for greater interaction with the intermediate-affinity IL-2R, and therefore drives the expansion of CD56bright natural killer (NK) cells. Furthermore, there appears to be a direct correlation between CD56bright NK cell expansion and DAC HYP efficacy in reducing relapses and MRI evidence of disease activity in patients with RMS in phase II and phase III double-blind, placebo- and active comparator-controlled trials. Therapeutic efficacy was maintained during open-label extension studies. However, treatment was associated with an increased risk of rare adverse events, including cutaneous inflammation, autoimmune hepatitis, central nervous system Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) syndrome, and autoimmune Glial Fibrillary Acidic Protein (GFAP) alpha immunoglobulin-associated encephalitis. As a result, DAC HYP was removed from clinical use in 2018. The lingering importance of DAC is that its use led to a deeper understanding of the underappreciated role of innate immunity in the potential treatment of autoimmune disease. View Full-Text
Keywords: daclizumab; relapsing multiple sclerosis; CD25; innate immune system; interleukin-2; drug reaction with eosinophilia systemic symptoms; DRESS; autoimmunity daclizumab; relapsing multiple sclerosis; CD25; innate immune system; interleukin-2; drug reaction with eosinophilia systemic symptoms; DRESS; autoimmunity
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Cohan, S.L.; Lucassen, E.B.; Romba, M.C.; Linch, S.N. Daclizumab: Mechanisms of Action, Therapeutic Efficacy, Adverse Events and Its Uncovering the Potential Role of Innate Immune System Recruitment as a Treatment Strategy for Relapsing Multiple Sclerosis. Biomedicines 2019, 7, 18.

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