In developing biological drugs, scientists often rely on Chinese hamster ovary (CHO) cells for early studies. To produce a CHO cell line that can be used in production, scientists use single-cell cloning. “Despite general use, knowledge of the effects of this process is limited,” wrote Marcus Weinguny—then a doctoral student at the Austrian Centre of Industrial Biotechnology in Vienna and now a process expert at Pfizer—and his colleagues in a recent study.
For one thing, the single-clone cells are not all alike. As Weinguny notes, the cells “display a wide array of observed phenotypes.” These scientists showed that phenotypic variations arise from changes in the DNA of the cells, including differences in methylation patterns. From analyzing CHO cell lines, Weinguny and his colleagues found that “the transcriptome of each subclone also had a significant number of individual changes,” and the scientists pointed out that such changes “indicate that epigenetic regulation is a hidden, but important player in cell line development with a major role in the establishment of high performing clones with improved characteristics for bioprocessing.”
Other experts agree on the value of reliable CHO cell lines.
“Technologies and methods that result in the development and identification of robust and stable CHO pools and clones that can be paired with platform media, feed, and bioprocesses will be imperative for reducing timelines,” says Oren Beske, amalgamator of business and biology, ATUM. In particular, he says, scientists need “technologies and methods enabling rapid post-transfection selection, early decision making—using analytical methods from small volumes—and wild type, or faster, doubling times whilst attaining high titers and robust stability.”
The CHO cells also must be easy to work with and flexible. “These cells should be robust such that a relatively generic platform process, such as one for monoclonal antibodies, could be applied with very little or no process development to rapidly create bulk drug substance for Phase I clinical trials,” Beske says.
Overall, he points out that biopharma needs “CHO pools and clones that can rapidly be scaled up to the appropriate scale without process development and with a low-risk profile.”
Given the wide use of CHO cells, reliable and vigorous lines are exactly what researchers and drug developers need.