Recombinant Prothrombin Therapy for Hemorrhage

重组凝血酶原治疗出血

基本信息

批准号：
9404172
负责人：
Soon Seog Jeong
金额：
$ 29.96万
依托单位：
HUMAN CELL CO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-11 至 2020-08-10
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9404172
关键词：
Admission activity Aftercare Animals Anticoagulation Bioreactors Blood Cells Blood Coagulation Disorders Blood Coagulation Factor Blood Coagulation Factor VII Blood Platelets Blood Transfusion Cell Culture Techniques Cell Density Cell Line Cells Cessation of life Chemicals Chinese Hamster Ovary Cell Clinical Treatment Clone Cells Coagulation Factor Deficiency Coagulation Process Complex Complication Consumption Data Development Disseminated Intravascular Coagulation Dose Endotoxins Erythrocytes FDA approved Factor VIIa Family suidae Fibrinogen Financial compensation Fresh Frozen Plasmas Generations Growth Guidelines Hemorrhage Hemorrhagic Shock Hemostatic Agents Hospitals Hour Human Licensing Life Liquid substance Modeling Operating Rooms Oral Patients Peptide Signal Sequences Phase Physiological Placebos Plasma Post-Translational Protein Processing Production Proteins Prothrombin Recombinants Recommendation Reporting Risk Safety Serum Suspensions System Technology Thrombin Thromboembolism Transfusion Trauma Trauma patient United States Vitamin K Vitamin K Deficiency blood product carboxylation cell bank comparative efficacy control trial cost cost effective drotrecogin alfa improved in vivo liver injury lung injury mortality promoter prothrombin complex concentrates recombinant FVIIa scale up therapeutic protein

项目摘要

Uncontrolled bleeding remains one of the leading causes of trauma-induced death. Current treatment recommendations focus on fresh frozen plasma and blood cell transfusions which do not seem to be effective. Over the last few years, these is increasing use of prothrombin complex cencentrate to treat hemorrhage-associated coagulapathy which is effective but induces disseminated intravascular coagulation. Recent animal studies demonstarte that different from prothrombin complex cencentrate, recombinant human prothrombin (factor II) from CHO cells as monotherapy effectively reduced blood loss and improved survival without causing thromboembolism. However, CHO cell is not adequate for cost-effective and functional production. Our preliminary sudies indicate that HEK293 is a highly prefered host that enables high expression level and adequate post-translational modifications. We propose to optimize the production of human recombinant prothrombin from HEK293 cells and compare the efficacy and safety with prothrombin complex concentrate in a porcine model of dilutional coagulapthy.

不受控制的出血仍然是创伤引起的死亡的主要原因之一。当前的治疗建议集中于新鲜的冷冻血浆和输血，这些血浆似乎无效。在过去的几年中，这些是越来越多的使用凝血酶蛋白复合物裁判术来治疗与出血相关的凝血症，这是有效的，但诱导了散布的血管内凝血。最近的动物研究脱离了与凝血酶原络合术，重组的人类凝血酶素（因子II）不同，从而有效地减少了失血和改善的生存率，而不会引起血栓栓塞。但是，CHO细胞不足以用于具有成本效益和功能性生产。我们的初步Sudies表明，HEK293是一个高度偏爱的宿主，可以实现高表达水平和足够的翻译后修饰。我们建议在HEK293细胞中优化人类重组凝血酶原的产生，并将其在稀释性凝结型猪模型中与凝血酶原络合物浓缩物进行比较。