Therapeutic targeting of immune checkpoints has garnered significant attention in the area of cancer immunotherapy, in which efforts have focused in particular on cytotoxic T lymphocyte antigen 4 (CTLA4) and PD1, both of which are members of the CD28 family. In autoimmunity, these same pathways can be targeted to opposite effect: to curb the over-exuberant immune response. The CTLA4 checkpoint serves as an exemplar, whereby CTLA4 activity is blocked by antibodies in cancer immunotherapy and augmented by the provision of soluble CTLA4 in autoimmunity. Here, we review the targeting of co-stimulatory molecules in autoimmune diseases, focusing in particular on agents directed at members of the CD28 or tumour necrosis factor receptor families. We present the state of the art in co-stimulatory blockade approaches, including rational combinations of immune inhibitory agents, and discuss the future opportunities and challenges in this field.

免疫检查点的治疗靶向在癌症免疫治疗领域引起了极大的关注，其中努力特别集中在细胞毒性 T 淋巴细胞抗原 4 (CTLA4) 和 PD1 上，这两者都是 CD28 家族的成员。在自身免疫中，这些相同的途径可以针对相反的效果：抑制过度旺盛的免疫反应。CTLA4 检查点就是一个例子，CTLA4 活性在癌症免疫治疗中被抗体阻断，并通过在自身免疫中提供可溶性 CTLA4 来增强。在这里，我们回顾了共刺激分子在自身免疫性疾病中的靶向作用，特别关注针对 CD28 或肿瘤坏死因子受体家族成员的药物。我们展示了共刺激阻断方法的最新技术，