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.

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.

Publication date: Mar 11, 2019

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 CD56 natural killer (NK) cells. Furthermore, there appears to be a direct correlation between CD56 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.

Cohan, S.L., Lucassen, E.B., Romba, M.C., and 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. 17504. 2019 Biomedicines (7):1.

Concepts Keywords
Affinity MRI
Apoptosis Alpha
Autoimmune Apoptosis
Autoimmune Disease T cell
Autoimmune Hepatitis IL2RA
Bioavailability Interleukin 2
Blockade Immune system
CD25 Immunosuppressants
CD56 Genentech
Central Nervous System Daclizumab
Comparator Monoclonal antibodies
Correlation Immunology
DAC Branches of biology
Double Blind Medicine
Encephalitis Medical specialties
Eosinophilia Encephalitis
GFAP
Humanized Monoclonal Antibody
Immunoglobulin
Inflammation
Innate Immunity
Interleukin 2
MRI
Multiple Sclerosis
Natural Killer
NK Cells
Phase III
Placebo
Receptor
T Cell

Semantics

Type Source Name
disease MESH autoimmunity
disease DOID autoimmune disease
disease MESH autoimmune disease
gene UNIPROT SMIM10L2A
gene UNIPROT SMIM10L2B
disease DOID encephalitis
disease MESH encephalitis
gene UNIPROT GFAP
disease DOID syndrome
disease MESH syndrome
disease DOID Eosinophilia
disease MESH Eosinophilia
disease DOID autoimmune hepatitis
disease MESH autoimmune hepatitis
disease MESH inflammation
gene UNIPROT CYREN
disease MESH relapses
gene UNIPROT TNFRSF10B
gene UNIPROT NCAM1
gene UNIPROT IL2
gene UNIPROT PHEX
disease MESH HYP
gene UNIPROT IL2RA
gene UNIPROT ISG20
gene UNIPROT AADAC
gene UNIPROT FBXW4
disease DOID Multiple Sclerosis
disease MESH Multiple Sclerosis
pathway BSID Innate Immune System
drug DRUGBANK Daclizumab

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