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.
Public Health Relevance Statement: Human Cell Co will use its proprietary technology to produce recombinant human prothrombin at the scale, quality, and cost that will meet the requirements for the hemostatic monotherapy.
Project Terms: Admission activity; Aftercare; Animals; Anticoagulation; Bioreactors; Blood Cells; Blood Coagulation Disorders; Blood Coagulation Factor; Blood Coagulation Factor VII; Blood Platelets; blood product; Blood Transfusion; carboxylation; cell bank; 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; comparative efficacy; Complex; Complication; Consumption; control trial; cost; cost effective; Data; Development; Disseminated Intravascular Coagulation; Dose; drotrecogin alfa; Endotoxins; Erythrocytes; Factor VIIa; Family suidae; FDA approved; Fibrinogen; Financial compensation; Fresh Frozen Plasmas; Generations; Growth; Guidelines; Hemorrhage; Hemorrhagic Shock; Hemostatic Agents; Hospitals; Hour; Human; improved; in vivo; Licensing; Life; Liquid substance; liver injury; lung injury; Modeling; mortality; Operating Rooms; Oral; Patients; Peptide Signal Sequences; Phase; Physiological; Placebos; Plasma; Post-Translational Protein Processing; Production; promoter; Proteins; Prothrombin; prothrombin complex concentrates; recombinant FVIIa; Recombinants; Recommendation; Reporting; Risk; Safety; scale up; Serum; Suspensions; System; Technology; therapeutic protein; Thrombin; Thromboembolism; Transfusion; Trauma; Trauma patient; United States; Vitamin K; Vitamin K Deficiency
