INSERM, UMR643, Nantes F44093, France.
Immunotherapy. 2010 Sep;2(5):625-36. doi: 10.2217/imt.10.57.
In the early 1990s, Linsley and colleagues produced a soluble fusion protein, comprising of the extracellular domain of cytotoxic T lymphocyte antigen (CTLA)4 and the human IgG1 Fc domain. Since then, several hundreds of scientific publications have demonstrated that CTLA4-Ig blocks CD28-mediated co-stimulation and suppresses unwanted T cell-mediated responses in animal models of transplantation, autoimmunity and inflammation. In the past two decades, Bristol-Myers Squibb Co. has developed abatacept, a CTLA4-Ig molecule for treating psoriasis and rheumatoid arthritis, and belatacept, a second-generation, higher affinity CTLA4-Ig molecule for use in kidney transplantation. Belatacept represents a new class of transplantation immunosuppressants and potentially offers clinicians a breakthrough therapy to preserve kidney function in the long term and reduce the side effects of current immunosuppressive therapies.
在 20 世纪 90 年代早期，林斯利（Linsley）及其同事们生产了一种可溶性融合蛋白，由细胞毒性 T 淋巴细胞抗原（CTLA）4 的细胞外结构域和人 IgG1 Fc 结构域组成。从那时起，数百篇科学出版物已经证明 CTLA4-Ig 阻断 CD28 介导的共刺激，并在移植、自身免疫和炎症的动物模型中抑制不需要的 T 细胞介导的反应。在过去的二十年中，百时美施贵宝公司（Bristol-Myers Squibb Co.）开发了阿巴西普（abatacept），一种用于治疗银屑病和类风湿关节炎的 CTLA4-Ig 分子，以及贝利尤单抗（belatacept），一种第二代、更高亲和力的 CTLA4-Ig 分子，用于肾移植。贝利尤单抗代表了一类新的移植免疫抑制剂，为临床医生提供了一种潜在的突破性治疗方法，以长期维持肾功能并减少当前免疫抑制治疗的副作用。
