The use of Chinese hamster ovary, or CHO, cells in cell line development — particularly for the production of biopharmaceuticals — stands as a testament to the intersection of historical serendipity and scientific ingenuity. Understanding why contract development and manufacturing organizations (CDMOs) prefer CHO cells over other cell types for biopharmaceutical production reveals a fascinating blend of history, biology, and technological innovation.
The Origins of CHO Cells
The story of CHO cells begins in 1948, when Robert Briggs Watson, a physician with the Rockefeller Foundation, transported a group of Chinese ground hamsters from China to the United States. These hamsters were initially used for studying various infections and diseases in epidemiological research.
However, their role in scientific research took a significant turn in 1957 when Theodore T. Puck and Fa-Ten Kao of the University of Colorado Medical Center isolated CHO cells from these hamsters, meaning they could be cultured and studied in the lab. This marked the beginning of the use of CHO cells in scientific research and biopharmaceutical production.
CHO cells demonstrated several unique characteristics that made them suitable for scientific experimentation and, eventually, industrial applications. These cells exhibited rapid suspension growth and high protein expression, features highly desirable in the field of biopharmaceutical production. Their ability to grow in suspension cultures made them easier to cultivate in large quantities, a necessity for industrial-scale cell line development.
The Breakthrough in Biopharmaceutical Production
The potential of CHO cells was more fully realized in the 1980s when biotechnology companies began to harness their capabilities for producing recombinant proteins. In 1984, Genentech achieved a major milestone by using recombinant CHO cells to express tissue-type plasminogen activator, a protein critical in the treatment of blood clots. This was both a scientific achievement and a commercial success — t-PA was approved for marketing in 1987, marking the first instance of a protein drug produced using mammalian cell expression systems being commercially available.
Following these initial successes, the popularity of CHO cells in laboratories and industry soared. Scientists successfully isolated different subtypes of CHO cell lines, each with specific characteristics tailored to varying research and production needs. These subtypes included CHO-S, CHO DXB11, CHO DG44, and CHO-M, among others.
The continuous attention to gene knockouts in CHO cells led to the development of specialized lines such as Samsung Biologics’ S-CHOice®. These advancements expanded the versatility and efficiency of CHO cells in producing a wide range of biopharmaceuticals, including coagulation factors, erythropoietin, immunoglobulin, and monoclonal antibodies.
Initially, CHO cells were cultured in media supplemented with fetal bovine serum, but this approach had limitations like batch-to-batch variability and risk of contamination. Over time, the development of serum-free media has revolutionized CHO cell culture. These media are more consistent, reduce contamination risks, and improve the overall quality of the biopharmaceuticals produced. Today, a typical serum-free medium for CHO cells contains a precise blend of amino acids, vitamins, trace elements, growth factors, and more, optimizing cell growth and protein production.
The Advantages of CHOs in Cell Line Development
CHO cells are now the most widely used mammalian cell line for the mass production of therapeutic proteins. They possess the capability to produce recombinant proteins on a scale of 3 to 10 grams per liter of culture, making them highly efficient for industrial cell line development purposes. One of the key advantages of CHO cells is their ability to allow post-translational modifications to recombinant proteins, which are crucial for human applications.
CHO cells facilitate proper folding, glycosylation, and other modifications necessary for the biological activity of proteins in humans. Because they can produce a significant amount of protein per liter of culture and demonstrate robustness in various culture conditions, they facilitate flexible large-scale production.
The adoption of CHO cells in biopharmaceutical production has been driven by their unparalleled efficiency in producing human-compatible proteins. Their ability to perform necessary post-translational modifications has made them the cell line of choice for creating complex biological products. It’s estimated that approximately 70% of biologics and almost all monoclonal antibodies have been produced using CHO cells.
CHOs and the Future of Medicine
The story of CHO cells, from their initial isolation to their pivotal role in modern biopharmaceutical production, presents a remarkable example of scientific advancement. CHO cells’ unique properties, coupled with continuous improvements in cell line development technology, have made CHOs an indispensable tool in the production of therapeutic proteins that ultimately save lives.
Biopharmaceuticals represent a growing segment of the broader pharmaceutical industry, with ongoing development of biologic treatments for conditions ranging from autoimmune diseases to cancer. As such, the significance of CHO cells in the pharmaceutical landscape is likely to grow, underlining their perhaps surprising, but enduring, importance in advancing human health and medicine.