SGER: Responses of Mammalian Cells to Increased Osmolarity: Effects on Antibody Productivity

SGER：哺乳动物细胞对渗透压增加的反应：对抗体生产力的影响

• 批准号: 0811639
• 负责人: Susan Sharfstein
• 金额: --
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0811639&HistoricalAwards=false
• 关键词: SGER; Responses; Mammalian; Cells; Increased

CBET-0811639, SharfsteinMonoclonal antibodies and Fc-fusion proteins produced in cultured mammalian cells represent a significant fraction of the recently approved and pipeline biopharmaceuticals, providing critical new therapies for diseases such as breast cancer and rheumatoid arthritis. Despite the widespread use of mammalian cell cultures for production of immunoglobulins and immunoglobulin-like compounds, many fundamental questions about cell physiology and culture conditions, and their role in production of these proteins, remain unanswered. In particular, elevated culture osmolarity, whether directly applied or as a result of feeding strategies, has been shown been shown to increase specific productivity but to decrease overall viable cell density. This project is a multidisciplinary research program to understand the physiological responses of cultured mammalian cells to hyperosmolarity and to design cellular and process engineering strategies to optimize protein production in response to hyperosmolarity.

CBET-0811639，Sharfstein在培养的哺乳动物细胞中产生的单克隆抗体和Fc融合蛋白代表了最近批准和管道生物制药的重要部分，为乳腺癌和类风湿性关节炎等疾病提供了关键的新疗法。尽管哺乳动物细胞培养物广泛用于生产免疫球蛋白和免疫球蛋白样化合物，但关于细胞生理学和培养条件及其在这些蛋白质生产中的作用的许多基本问题仍然没有答案。特别是，升高的培养物渗透压，无论是直接应用还是作为补料策略的结果，都已显示出增加比生产率，但降低总活细胞密度。该项目是一个多学科的研究计划，以了解培养的哺乳动物细胞对高渗的生理反应，并设计细胞和工艺工程策略，以优化蛋白质生产响应高渗。