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

在培养的哺乳动物细胞中产生的CBET-0811639、Sharfstein单抗和Fc融合蛋白是最近批准的和流水线生物制药中的一个重要组成部分，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被广泛用于生产免疫球蛋白和免疫球蛋白样化合物，但许多关于细胞生理学和培养条件及其在生产这些蛋白质中的作用的基本问题仍然没有答案。特别是，提高培养渗透压，无论是直接应用还是作为喂养策略的结果，已被证明增加了特定的生产力，但降低了总体活细胞密度。该项目是一个多学科的研究项目，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，以优化蛋白质生产以响应高渗透压。

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.