Abstract：
Targeting immune receptors on T cells is a common strategy to treat cancer and autoimmunity. Frequently, this is accomplished through monoclonal antibodies targeting the ligand binding sites of stimulatory or inhibitory co-receptors. Blocking ligand binding prevents downstream signalling and modulates specific T cell functions. Since 1985, the FDA has approved over 100 monoclonal antibodies against immune receptors. This therapeutic approach significantly improved the care of patients with numerous immune-related conditions; however, many patients are unresponsive, and some develop immune-related adverse events. One reason for that is the lack of consideration for the localization of these receptors on the cell surface of the immune cells in the context of the immune synapse. In addition to blocking ligand binding, changing the location of these receptors on the cell surface within the different compartments of the immunological synapse could serve as an alternative, efficient, and safer approach to treating these patients. This review discusses the potential therapeutic advantages of altering proteins\' localization within the immune synapse and summarizes published work in this field. It also discusses the novel use of bispecific antibodies to induce the clustering of receptors on the cell surface. It presents the rationale for developing novel antibodies, targeting the organization of signalling receptor complexes on the cell surface. This approach offers an innovative and emerging technology to treat cancer patients resistant to current immunotherapies.
摘要：
靶向T细胞上的免疫受体是治疗癌症和自身免疫的常见策略。经常,这是通过靶向刺激性或抑制性共受体的配体结合位点的单克隆抗体来实现的。阻断配体结合防止下游信号传导并调节特异性T细胞功能。自1985年以来，FDA已经批准了100多种针对免疫受体的单克隆抗体。这种治疗方法显着改善了许多免疫相关疾病患者的护理;然而，许多患者反应迟钝，和一些发展免疫相关的不良事件。其一个原因是在免疫突触的背景下缺乏对这些受体在免疫细胞的细胞表面上的定位的考虑。除了阻断配体结合，改变这些受体在免疫突触的不同区室中的细胞表面上的位置可以作为替代方案，高效,和更安全的方法来治疗这些患者。这篇综述讨论了改变蛋白质在免疫突触内定位的潜在治疗优势，并总结了该领域已发表的工作。它还讨论了双特异性抗体在细胞表面上诱导受体聚集的新用途。它提出了开发新抗体的基本原理，靶向细胞表面上的信号受体复合物的组织。这种方法提供了一种创新的新兴技术来治疗对当前免疫疗法有抗性的癌症患者。
