Monoclonal antibodies hold a steadfast lead in the ever-expanding biologics marketplace and have revolutionized the treatment of a wide variety of illnesses. The prominence of mAbs as therapeutic agents brought with it the need for large scale production of these drugs, which in turn highlighted the need for improvements in cell culture processes to raise product titres. Increased product titres shifted bioprocessing concerns downstream as with increased titre brought along the increased expression of unwanted host cell proteins (HCPs). HCPs are a highly diverse range of proteins. While some HCPs can be degradative to the product itself, others could induce an unwanted immune response compromising the safety and efficacy of the biologic. Enzyme-linked immunosorbent assays (ELISAs) are currently the gold standard for release testing for HCPs. ELISAs provide quantitative measurement of total HCP levels but have several limitations. Industry has shifted towards the use of orthogonal methods to support process development and validation with a particular focus on analytical tools such as LC–MS/MS.

This review discusses the current methods for identification and analysis of problematic HCPs in CHO cell lines used for mAb bioprocessing.

单克隆抗体在不断扩展的生物制剂市场上一直保持领先地位，并彻底改变了多种疾病的治疗方法。mAb作为治疗剂的突出地位，带来了对这些药物的大规模生产的需求，这反过来又凸显了对改进细胞培养过程以提高产品滴定度的需求。产品滴度的增加将生物工艺问题转移到下游，因为滴度的增加会导致有害宿主细胞蛋白（HCP）的表达增加。HCP是种类繁多的蛋白质。虽然某些HCP可能会降解产品本身，但其他一些HCP可能会导致有害的免疫反应，从而损害生物制剂的安全性和有效性。酶联免疫吸附测定（ELISA）是目前HCP释放测试的金标准。ELISA提供了总HCP水平的定量测量，但有一些限制。工业已经转向使用正交方法来支持过程开发和验证，尤其侧重于LC-MS / MS等分析工具。

这篇综述讨论了用于鉴定和分析用于mAb生物加工的CHO细胞系中有问题的HCP的当前方法。