Recombinant Human Serum Albumin for Use in Cell Culture

描述(由申请人提供)：血浆来源的人血清白蛋白(PHSA)或牛血清白蛋白通常添加到细胞培养基疫苗和治疗生产中使用的细胞培养液中，因为它可以促进细胞生长和提高蛋白质生产率。然而，使用PHSA有传播病毒和新出现的传染病病原体的风险，特别是对于那些无法进行检测的病原体。由于每年有数百万人接受基于细胞培养的疫苗接种，还有数百万人需要基于细胞培养的疗法来治疗各种疾病，监管机构呼吁用重组人血清白蛋白(RHSA)取代疫苗和治疗生产中的PHSA。在第一阶段的可行性研究中，我们发现大米中的重组人血清白蛋白不仅可以替代PHSA，而且在促进细胞生长和产生抗体方面都比PHSA高51%和50%。在第二阶段，我们将扩展第一阶段的研究，以测试重组人血清白蛋白对杂交瘤、CHO和Vero细胞在商业培养基大规模细胞培养中的细胞生长和生产力的影响。我们还将尝试确定哪些因素(S)是导致我们从大米中制备的重组人血清白蛋白制剂具有优异性能的原因。我们将启动提高粮食产量的育种计划，进一步降低RHSA生产成本。我们预计，在第二阶段研究结束时，我们的项目将响应监管机构的呼吁，通过向市场提供性能优越的RHSA，在疫苗和治疗生产中找到安全的PHSA替代品。公共卫生相关性：由于使用血浆来源的人血清白蛋白(PHSA)和血液产品作为细胞培养液中用于细胞疫苗和治疗生产的成分，新出现的传染病病原体在人与人之间传播存在安全问题。监管机构呼吁用重组人血清白蛋白取代PHSA。对此，用大米生产的重组人血清白蛋白的廉价来源不仅将确保PHSA的安全替代品，而且还将使以细胞为基础的疫苗和治疗药物的生产具有成本效益。

DESCRIPTION (provided by applicant): Plasma-derived human serum albumin (pHSA) or bovine serum albumin are commonly added to cell culture media used in cell culture-based vaccine and therapeutic production, because it enhances cell growth and increases protein productivity. However, the use of pHSA carries the risk of transmission of viruses and emerging infectious pathogens, particularly for those for which no tests are available. Because millions of people are immunized annually with cell culture- based vaccines and millions more require cell culture-based therapeutics for the treatment of various disorders, regulatory agencies have called for a replacement of pHSA in vaccine and therapeutic production with recombinant HSA (rHSA). In Phase I feasibility study, we showed that rHSA from rice can not only be used to replace pHSA but also outperform pHSA by 51% in cell growth enhancement and by 50% in antibody production. In phase II, we will extend the studies in phase I to test the effect of rHSA on cell growth and productivity of hybridoma, CHO and Vero cells in larger scale cell culture with commercial media. We will also attempt to identify which factor(s) is (are) responsible for the superior performance of our rHSA preparation from rice. We will initiate a breeding program to improve the grain yield so to further reduce cost rHSA production. We anticipate that at the end of phase II studies, our project will have addressed the call by regulatory agencies for a safe alternative to pHSA in vaccine and therapeutic production by providing to the market rHSA with superior performance. Public Health Relevance: Safety concerns regarding human-to-human transmission of emerging infectious pathogens from the use of plasma-derived human serum albumin (pHSA) and blood products as an ingredient in cell culture media for cell-based vaccine and therapeutic production exist. Regulatory agencies have called for the replacement of pHSA with recombinant HSA. In response, an inexpensive source of recombinant HSA produced in rice would not only assure a safe alternative to pHSA, but would also allow cost- effective production of cell-based vaccine and therapeutics.