Department of Chemical Engineering, University of Massachusetts Lowell, Lowell, Massachusetts.
Biotechnol Bioeng. 2019 Dec;116(12):3446-3456. doi: 10.1002/bit.27140. Epub 2019 Aug 30.
Trace metals are supplied to chemically-defined media (CDM) for optimal Chinese hamster ovary (CHO) cell culture performance during the production of monoclonal antibodies and other therapeutic proteins. However, lot-to-lot and vendor-to-vendor variability in raw materials consequently leads to an imbalance of trace metals that are supplied to CDM. This imbalance can yield detrimental effects rooted in several primary mechanisms and pathways including oxidative stress, apoptosis, lactate accumulation, and unfavorable glycan synthesis. Recent research endeavors involve supplying zinc, copper, and manganese to CDM in excess to further maximize culture productivity and product quality. These treatments significantly impact critical quality attributes and furthermore highlight the degree to which trace metal availability can affect CHO cell culture performance. This review highlights the role of trace metal variability, supplementation, and interplay on key cellular mechanisms responsible for overall culture performance and the production and quality of therapeutic proteins.
痕量金属被供应给化学定义的培养基（CDM），以在生产单克隆抗体和其他治疗性蛋白质期间实现最佳的中国仓鼠卵巢（CHO）细胞培养性能。然而，原材料的批间和供应商间的可变性导致供应给 CDM 的痕量金属失去平衡。这种不平衡会产生有害影响，其根源在于几种主要的机制和途径，包括氧化应激、细胞凋亡、乳酸积累和不利的聚糖合成。最近的研究工作涉及向 CDM 中过量供应锌、铜和锰，以进一步最大限度地提高培养生产力和产品质量。这些处理方法会显著影响关键质量属性，并且进一步强调了痕量金属的可用性对 CHO 细胞培养性能的影响程度。本综述重点介绍了痕量金属变异性、补充和相互作用对负责整体培养性能以及治疗性蛋白质生产和质量的关键细胞机制的作用。
