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

CBET-0811639， sharfstein单克隆抗体和fc融合蛋白在培养的哺乳动物细胞中产生，代表了最近批准和正在开发的生物制药的很大一部分，为乳腺癌和类风湿性关节炎等疾病提供了重要的新疗法。尽管哺乳动物细胞培养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未得到解答。特别是，升高的培养渗透压，无论是直接应用还是作为喂养策略的结果，已被证明可以提高特定生产力，但会降低总体活细胞密度。该项目是一个多学科研究项目，旨在了解培养的哺乳动物细胞对高渗透压的生理反应，并设计细胞和过程工程策略来优化高渗透压下的蛋白质生产。

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.