Bhoskar Prachi, Belongia Brett, Smith Robert, Yoon Seongkyu, Carter Tyler, Xu Jin
Dept. of Chemistry, University of Massachusetts Lowell, Lowell, MA.
Biotechnol Prog. 2013 Sep-Oct;29(5):1131-9. doi: 10.1002/btpr.1767. Epub 2013 Jun 25.
Monoclonal antibodies (mAbs) are currently the dominant class of biopharmaceuticals. Due to the high dosage requirements of most mAb therapeutics, high productivity and low aggregation are prevailing criteria during cell line generation and process development. Given that light chains (LCs) play an important role in antibody folding and assembly, and that most mAb producing cell lines also manufacture free LCs, we sought to investigate whether there was a relationship between free LC levels in cell culture media and mAb productivity/quality. To this end, a series of analytical methods were developed in order to quantify free LC content in cell culture media and assess mAb productivity and aggregation levels. Afterwards, conditioned media samples from different cell lines at identical culturing conditions and a single clone under varying culturing conditions were analyzed. Higher LC expression was found to correlate with higher cell viability, higher mAb productivity, and lower aggregation. While LC expression cannot yet be definitively considered the root cause of these phenomena, these results are consistent with the role of LCs in mAb production, suggesting that free LC expression levels may potentially serve as a parameter for cell line generation and cell culture process optimization.
单克隆抗体（mAb）是目前生物制药的主导类别。由于大多数mAb治疗药物的剂量需求较高，在细胞系生成和工艺开发过程中，高生产率和低聚集是普遍的标准。鉴于轻链（LC）在抗体折叠和组装中起重要作用，并且大多数产生mAb的细胞系也会产生游离轻链，我们试图研究细胞培养基中游离轻链水平与mAb生产率/质量之间是否存在关联。为此，开发了一系列分析方法，以定量细胞培养基中的游离轻链含量，并评估mAb的生产率和聚集水平。之后，对来自相同培养条件下不同细胞系以及不同培养条件下单个克隆的条件培养基样本进行了分析。发现较高的轻链表达与较高的细胞活力、较高的mAb生产率和较低的聚集相关。虽然轻链表达尚未被明确视为这些现象的根本原因，但这些结果与轻链在mAb生产中的作用一致，表明游离轻链表达水平可能潜在地作为细胞系生成和细胞培养工艺优化的一个参数。
