König Martin, Rharbaoui Faiza, Aigner Silke, Dälken Benjamin, Schüttrumpf Jörg
Biotest AG , Dreieich , Germany.
Front Immunol. 2016 Jan 25;7:11. doi: 10.3389/fimmu.2016.00011. eCollection 2016.
Regulatory T cells (Tregs) represent a subpopulation of CD4(+) T cells, which are essential for the maintenance of immunological tolerance. The absence or dysfunction of Tregs can lead to autoimmunity and allergies. The restoration of functional Tregs and/or Treg cell numbers represents a novel and attractive approach for the treatment of autoimmune diseases, e.g., rheumatoid arthritis (RA). The CD4 cell surface receptor is a target for modulation of T cell function. Monoclonal antibodies (mAbs) against CD4 have previously been tested for the treatment of autoimmune diseases, including RA. Furthermore, in model systems, anti-CD4 antibodies are able to induce tolerance and mediate immunomodulatory effects through a variety of mechanisms. Despite the availability of innovative and effective therapies for RA, many patients still have persistently active disease or experience adverse events that can limit use. A growing body of evidence suggests that Treg modulation could offer a new therapeutic strategy in RA and other autoimmune disorders. Here, we describe tregalizumab (BT-061), which is a novel, non-depleting IgG1 mAb that binds to a unique epitope of CD4. Tregalizumab represents the first humanized anti-CD4 mAb that selectively induces Treg activation.
调节性T细胞（Tregs）是CD4(+) T细胞的一个亚群，对维持免疫耐受至关重要。Tregs的缺失或功能障碍可导致自身免疫和过敏。恢复功能性Tregs和/或Treg细胞数量是治疗自身免疫性疾病（如类风湿性关节炎（RA））的一种新颖且有吸引力的方法。CD4细胞表面受体是调节T细胞功能的靶点。抗CD4单克隆抗体（mAbs）此前已被用于测试治疗包括RA在内的自身免疫性疾病。此外，在模型系统中，抗CD4抗体能够通过多种机制诱导耐受并介导免疫调节作用。尽管有创新且有效的RA治疗方法，但许多患者仍有持续的活动性疾病或经历可能限制治疗使用的不良事件。越来越多的证据表明，Treg调节可为RA和其他自身免疫性疾病提供一种新的治疗策略。在此，我们描述了tregalizumab（BT - 061），它是一种新型的、非耗竭性IgG1 mAb，可结合CD4的独特表位。Tregalizumab是首个选择性诱导Treg激活的人源化抗CD4 mAb。
