下调人类免疫细胞活化的特异性双功能BY-001(嵌合蛋白PD-L1/Fc-gamma1的同源多聚体组合成的活性成分)及其应用

文档序号:620546 发布日期:2021-05-07 浏览:7次 >En<

阅读说明:本技术 下调人类免疫细胞活化的特异性双功能BY-001(嵌合蛋白PD-L1/Fc-gamma1的同源多聚体组合成的活性成分)及其应用 (Specific bifunctional BY-001 (active ingredient combined BY homomultimer of chimeric protein PD-L1/Fc-gamma 1) for down-regulating human immune cell activation and application thereof ) 是由 陆云彪 于 2019-06-06 设计创作,主要内容包括:本发明所展示的是嵌合蛋白PD-L1/Fc-gamma 1(BY-001)的同源多聚体的活性形式,而这种同源多聚体可以有25%的二聚体,30%的四聚体和45%的六聚体的组成。处于聚合状态下的BY-001由两个不同功能的结构域组成,其中一个是PD-L1的细胞外结构域,另一个是IgG1 Fc功能结构域。处于聚合状态的PD-L1作为第一功能结构域能更有效地抑制CD3+和CD28+的T细胞活性;而另一个功能结构域,处于聚合状态的FC-gamma1可以对带有Fc-gamma受体的免疫细胞也产生抑制作用。因此,本发明提供的实验结果表明BY-001可以调节负责外周免疫耐受的免疫细胞亚群的功能,这使得BY-001具有帮助恢复或维持人体外周免疫耐受从而达到治疗自身免疫性疾病的潜力,以及也可以保护受者接受同种异体移植后的异体器官。(The active form of the homomultimer of the chimeric protein PD-L1/Fc-gamma1(BY-001) is shown in the present invention, and this homomultimer may consist of 25% dimer, 30% tetramer and 45% hexamer. BY-001 in the polymerized state consists of two domains with different functions, one of which is the extracellular domain of PD-L1 and the other is the IgG1Fc functional domain. PD-L1 in a polymerized state as a first functional domain can more effectively inhibit the T cell activity of CD3&#43; and CD28 &#43;; while the other functional domain, FC-gamma1 in its polymerized state, may also exert an inhibitory effect on immune cells bearing Fc-gamma receptors. Therefore, the experimental results provided BY the invention show that BY-001 can regulate the functions of the immune cell subsets responsible for peripheral immune tolerance, so that BY-001 has the potential of helping to recover or maintain the peripheral immune tolerance of a human body so as to treat autoimmune diseases, and can also protect the allogeneic organs of a recipient after the recipient receives allogeneic transplantation.)

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