Brown Marion H
Sir William Dunn School of Pathology, South Parks Rd, Oxford, OX1 3RE, UK.
Curr Drug Targets. 2016;17(6):619-29. doi: 10.2174/1389450116666150825120536.
CD6 has been exploited as a drug target as its expression is restricted, primarily to T cells, it has a well characterised cell surface ligand, CD166 and regulates T cell activation through a long cytoplasmic tail. CD6 can affect both the initiation and maintenance of T cell function in a negative and positive manner respectively so that it is important to understand these dual effects of a potential drug target. The effective mode of action of clinical monoclonal antibodies (mAbs) that recognise cell surface receptors including CD6 is commonly cytotoxic depletion of cells. It is not clear how current therapeutic strategies to target CD6 perturb function. With the benefit of new structural data, this review provides a critical analysis and interpretation of experiments in which various reagents have been tested and offers some suggestions as how more effective drugs may be developed.
CD6已被用作药物靶点,因为其表达主要局限于T细胞,它有一个特征明确的细胞表面配体CD166,并通过一个长的细胞质尾巴调节T细胞活化。CD6可以分别以阴性和阳性方式影响T细胞功能的起始和维持,因此了解潜在药物靶点的这些双重作用很重要。识别包括CD6在内的细胞表面受体的临床单克隆抗体(mAb)的有效作用模式通常是细胞的细胞毒性耗竭。目前针对CD6的治疗策略如何扰乱其功能尚不清楚。借助新的结构数据,本综述对测试各种试剂的实验进行了批判性分析和解读,并就如何开发更有效的药物提出了一些建议。