摘要
CD6分子是参与T细胞的调节泛T细胞标记标记物。虽然CD6的表达与人类自身免疫性疾病相关,但只有少数的治疗方法利用这种分子作为临床治疗疾病的靶点。CD6的生物学功能和作用机制尚不明确。该分子可能作为细胞内信号的调制器起到了双重作用。itolizumab是针对CD6的人源化单克隆抗体,它在古巴哈瓦那分子免疫学中心得到开发。其母小鼠抗体的ior-t1单克隆抗体,在80年代哈瓦那的肿瘤学和放射医学研究所已获得。本文对用ior-t1单克隆抗体或itolizumab治疗的古巴获得性自身免疫性疾病患者的临床数据进行了概述。此外,我们基于对最近位点突变和结构数据的分析,讨论了itolizumab的作用机理,这与以前的解释相比,指出cd6-cd166在细胞环境中相互作用的空间阻断。总的来说,临床研究表明,itolizumab用于风湿性关节炎和银屑病患者单药治疗时具有良好的临床效果和安全性。到目前为止,体外和体内研究表明,itolizumab具有抗炎及免疫调节作用。因此,itolizumab是治疗自身免疫性疾病如类风湿性关节炎、银屑病药物的新选择。
关键词: CD6
Current Drug Targets
Title:Therapeutic Targeting of CD6 in Autoimmune Diseases: A Review of Cuban Clinical Studies with the Antibodies IOR-T1 and Itolizumab
Volume: 17 Issue: 6
Author(s): Patricia Hernández, Ernesto Moreno, Lazaro E. Aira and Pedro C. Rodríguez
Affiliation:
关键词: CD6
摘要: The CD6 molecule is a pan T cell marker involved in T cell regulation. Although CD6 expression has been correlated with human autoimmune diseases, only a few therapeutic approaches are exploring this molecule as target in the clinic. The biological functions and mechanisms of actions of CD6 have not been definitively established. It is probable that this molecule plays a dual role as a modulator of intracellular signaling. Itolizumab is a humanized monoclonal antibody specific for human CD6, developed at the Center of Molecular Immunology in Havana, Cuba. Its parent murine antibody, the IOR-T1 mAb, had been obtained in the 80's at the Institute of Oncology and Radiology, also in Havana. This article provides an overview of the clinical data obtained in Cuban patients with autoimmune diseases who have been treated with IOR-T1 mAb or itolizumab. Furthermore, we discuss the possible mechanism of action of itolizumab basing the analysis on recent site mutagenesis and structural data, which, contrary to previous interpretations, points to a steric blocking of the CD6-CD166 interaction in the cellular context. Overall, the conducted clinical studies have demonstrated that itolizumab has favorable clinical effects and a safety profile when used as monotherapy in patients with rheumatoid arthritis and psoriasis. So far, in vitro and in vivo evidences indicate that itolizumab has immunomodulatory and anti-inflammatory effects. Hence, itolizumab represents a new therapeutic option for autoimmune diseases such as rheumatoid arthritis and psoriasis.
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Cite this article as:
Patricia Hernández, Ernesto Moreno, Lazaro E. Aira and Pedro C. Rodríguez , Therapeutic Targeting of CD6 in Autoimmune Diseases: A Review of Cuban Clinical Studies with the Antibodies IOR-T1 and Itolizumab, Current Drug Targets 2016; 17 (6) . https://dx.doi.org/10.2174/1389450117666160201114308
DOI https://dx.doi.org/10.2174/1389450117666160201114308 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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