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Spotlight on daclizumab: its potential in the treatment of multiple sclerosis

机译：达珠单抗的聚焦：其在多发性硬化症治疗中的潜力

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Multiple sclerosis (MS) is a chronic inflammatory-demyelinating disease of the central nervous system of a putative autoimmune etiology. Although the exact pathogenic mechanisms underlying demyelination and axonal damage in MS are not fully understood, T-cells are believed to play a central role in the pathogenesis of the disease. Daclizumab is a humanized binding monoclonal antibody that binds to the Tac epitope on the α-subunit (CD25) of the interleukin-2 (IL-2) receptor, thus effectively blocking the formation of the high-affinity IL-2 receptor, which is expressed mainly on T-cells. A series of clinical trials in patients with relapsing MS demonstrated a profound effect of daclizumab on inflammatory disease activity and improved clinical outcomes compared with placebo or interferon-β, which led to the recent approval of daclizumab (Zinbryta?) for the treatment of relapsing forms of MS. Enhancement of endogenous mechanisms of immune regulation rather than inhibition of effector T-cells might explain the effects of daclizumab in MS. These include expansion and improved function of regulatory CD56bright NK cells, inhibition of the early activation of T-cells through blockade of IL-2 transpresentation by dendritic cells and reduction in the number of intrathecal proinflammatory lymphoid tissue inducer cells. The enhanced efficacy of daclizumab is accompanied by an increased frequency of adverse events and risks of serious adverse events, thus placing it as a second-line therapy and calling for the implementation of a strict risk management program. This review details the mechanisms of action of daclizumab, discusses its efficacy and safety in patients with MS, and provides an insight into the place of this novel therapy in the treatment of MS.
机译：多发性硬化症（MS）是一种推定的自身免疫病因的中枢神经系统的慢性炎症性脱髓鞘疾病。尽管尚不完全了解MS中脱髓鞘和轴突损伤的确切致病机制，但据信T细胞在疾病的发病机理中起着核心作用。 Daclizumab是一种人源化结合单克隆抗体，可与白介素2（IL-2）受体的α-亚基（CD25）上的Tac表位结合，从而有效地阻止高亲和力的IL-2受体的形成。主要在T细胞上表达在患有复发性MS的患者中进行的一系列临床试验表明，与安慰剂或干扰素-β相比，达克珠单抗对炎性疾病活动具有深远的影响，并改善了临床结局，这导致达克珠单抗（Zinbryta？）最近被批准用于治疗复发型MS。增强免疫调节的内源性机制而不是抑制效应T细胞可能可以解释daclizumab在MS中的作用。这些包括调节性CD56 亮 NK细胞的扩增和功能改善，通过树突状细胞阻断IL-2的表达来抑制T细胞的早期活化，以及减少鞘内促炎性淋巴组织诱导剂的数量。细胞。达珠单抗的疗效增强伴随着不良事件发生频率的增加和严重不良事件风险的增加，因此将其作为二线治疗药物并呼吁实施严格的风险管理计划。这篇综述详细介绍了达克珠单抗的作用机制，讨论了其在MS患者中的疗效和安全性，并对这种新型疗法在MS治疗中的地位提供了见识。

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