The production of many therapies based on monoclonal antibodies relies on Chinese Hamster Ovary (CHO) cells. Unfortunately, these cells also make host cell proteins (HCPs), which can make a drug less effective and even set off immune responses in patients. So, manufacturers try to minimize HCPs in therapies developed with CHOs, but it’s a difficult task. Nonetheless, Sri Madabhushi, PhD, a principal scientist and director of biologics process R&D at Merck & Co. in Rahway, NJ, and her colleagues recently proposed a novel approach to the HCP battle.
Today, manufacturers often use cell viability as an indicator of lower levels of HCPs. The idea here is that lower viability goes together with cells releasing more HCPs, but that’s not what all studies find. As Madabhushi’s Merck team put it, “viability alone does not reliably predict HCP levels.”
Instead, these scientists used transcriptomics to analyze the HCPs, especially the problematic ones, in CHO cultures, and looked for an upstream solution. They found that the level of HCPs in a CHO depends on many factors. For example, different media used in culturing can change the kind of HCPs produced. The concentration and composition of HCPs in a culture also varied with the temperature at specific stages of the bioprocessing, the percentage of dissolved oxygen, and so on. By controlling these factors, the Merck scientists reduced the HCPs generated in a CHO-derived therapy.
As often happens in biology, one measurement is not enough to tell a story. Plus, as scientists delve deeper into a question, unexpected results can emerge. As Madabhushi and her colleagues concluded: “Surprisingly, our findings debunked the notion of viability as a primary indicator for controlling HCP levels, highlighting instead the significant influence of factors such as clone selection, host cell line, media, and process parameters.”
In short, a more accurate story in biology is often a more complicated one. That’s the case for controlling HCPs in CHO-developed therapeutics.