Ho Yingswan, Varley Julie, Mantalaris Athanasios
Department of Chemical Engineering, Imperial College London, South Kensington campus, London SW7 2AZ, United Kingdom.
Biotechnol Prog. 2006 Nov-Dec;22(6):1560-9. doi: 10.1021/bp060032b.
The GS-NS0 cell line is industrially important and is currently used for the large-scale production of several therapeutic monoclonal antibodies. A novel hybrid model, consisting of both unstructured and structured elements, has been developed to describe cell growth and death, metabolism, and antibody production in the GS-NS0 system under normal culture conditions. A comparison between the hybrid model and a large-scale single-cell model (SCM) describing detailed metabolic processes verified the predictive ability of the hybrid model (when compared with experimental data) and highlighted the practical difficulties involved in utilizing complex models. Global sensitivity analysis (GSA) on the hybrid model identified the specific transcription and translation rates of heavy and light immunoglobulin chains as parameters with the largest impact on the antibody production process. This information, together with the addition of a 24-h lag phase, resulted in the successful extension of the hybrid model to represent GS-NS0 system behavior under hyperosmotic culture conditions.
GS-NS0细胞系在工业上具有重要意义，目前用于大规模生产多种治疗性单克隆抗体。已开发出一种由非结构化和结构化元素组成的新型混合模型，用于描述正常培养条件下GS-NS0系统中的细胞生长与死亡、代谢及抗体产生。将该混合模型与描述详细代谢过程的大规模单细胞模型（SCM）进行比较，验证了混合模型的预测能力（与实验数据相比），并突出了使用复杂模型所涉及的实际困难。对混合模型进行的全局敏感性分析（GSA）确定，重链和轻链免疫球蛋白的特定转录和翻译速率是对抗体生产过程影响最大的参数。这些信息，再加上添加24小时的延迟期，使得混合模型得以成功扩展，以代表高渗培养条件下GS-NS0系统的行为。
