R&D Center, GC Pharma, 93 Ihyeon-ro 30 Beon-Gil, Giheung-gu, Yongin, 16924, Republic of Korea.
Graduate Program in Biomaterials Science and Engineering, Graduate School of Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Arch Pharm Res. 2020 Jul;43(7):714-723. doi: 10.1007/s12272-020-01245-y. Epub 2020 Jul 14.
Factor VIII (FVIII) is a blood coagulation protein that circulates as a complex with von Willebrand factor (vWF) in the plasma. In the survey of inhibitors in plasma product exposed toddlers (SIPPET) study, plasma-derived FVIII containing vWF was less immunogenic in hemophilia A patients than products with only high-purity FVIII only or recombinant FVIII. The FVIII purified by the conventional purification process using anion-exchange (AEX) chromatography had a low vWF content. In this study, purified vWF was added to the purified FVIII to increase the vWF content. The purified vWF was recovered from the discarded washing solution of the AEX chromatography using cation-exchange (CEX) chromatography. The vWF/FVIII complex had an abundance of high molecular weight vWF similar to the normal plasma, and a low reactivity of FVIII inhibitors. Furthermore, its efficacy was observed in a mouse model of hemophilia A. Therefore, the vWF/FVIII complex produced by our new purification method could be an effective and less immunogenic therapeutic agent for the hemophilia A and von Willebrand disease.
VIII 因子（FVIII）是一种血液凝血蛋白，在血浆中与血管性血友病因子（vWF）形成复合物循环。在血浆制品暴露的婴幼儿中抑制剂的调查研究（SIPPET）中，与仅含高纯度 FVIII 或重组 FVIII 的产品相比，含有 vWF 的血浆源性 FVIII 对血友病 A 患者的免疫原性较低。使用阴离子交换（AEX）色谱法的常规纯化工艺纯化的 FVIII 具有较低的 vWF 含量。在这项研究中，添加纯化的 vWF 以增加 vWF 含量。使用阳离子交换（CEX）色谱法从 AEX 色谱法的废弃洗涤溶液中回收纯化的 vWF。vWF/FVIII 复合物具有类似于正常血浆的高分子量 vWF 的丰富性，并且 FVIII 抑制剂的反应性较低。此外，在血友病 A 小鼠模型中观察到其疗效。因此，我们的新纯化方法生产的 vWF/FVIII 复合物可能是血友病 A 和血管性血友病的有效且免疫原性较低的治疗剂。
