Many advanced medicines for conditions like cancer and autoimmune disorders are produced by cells from a hamster, specifically a cell type known as Chinese Hamster Ovary (CHO) cells. For decades, these cells have been central to the biopharmaceutical industry, producing the majority of complex therapeutic proteins. The use of CHO cells allows for the creation of intricate protein-based drugs that are both effective and safe for human use, making them a foundation of modern biotechnology.
The Origin and Nature of CHO Cells
A cell line is a population of cells from a single source that can be cultured to grow and divide indefinitely in a laboratory. This “immortality” allows for a consistent and renewable supply of identical cells. While some cell lines are derived from tumors, others acquire this ability spontaneously.
CHO cells originated in 1957 when Dr. Theodore T. Puck isolated epithelial cells from the ovary of a female Chinese hamster (Cricetulus griseus). These cells thrived in lab conditions, spontaneously becoming an immortalized cell line. This original line is the ancestor of all CHO cells used in research and industry today.
Chinese hamsters were used in research partly because their low chromosome count was useful for genetic studies. Puck’s successful cultivation provided a robust mammalian cell line, a significant achievement for biotechnology.
Over the decades, this original line has been adapted into specialized variants like CHO-K1, CHO-S, and CHO-DG44. Each variant has specific traits, such as growing in different nutrient mixtures or being more easily genetically engineered. This refinement has solidified the position of CHO cells as a versatile tool for biological production.
Why CHO Cells are Used for Modern Medicine
CHO cells are used because of their sophisticated, human-like biology. Many therapeutic drugs are proteins, which are large, complex molecules. For these proteins to work correctly, they must be folded into a precise three-dimensional shape and often decorated with specific sugar molecules.
This process of adding sugars, known as glycosylation, is a post-translational modification (PTM) that affects a protein’s function and stability. If a human therapeutic protein has incorrect glycosylation, it may not work or could be targeted by the patient’s immune system. Simpler systems, like bacteria, lack the machinery for these complex, human-like modifications.
Because CHO cells are mammalian, their protein production machinery is very similar to that of humans. They perform the intricate folding and glycosylation required to produce functional and biocompatible proteins. While not identical to human patterns, the glycosylation is close enough that the drugs are safe and effective.
CHO cells also offer practical manufacturing advantages. They are robust, tolerate environmental variations, and grow in suspension within large bioreactors for industrial-scale production. Their long history of safe use and lower risk of carrying human viruses helps streamline regulatory approval.
Engineering CHO Cells for Therapeutic Production
CHO cells do not naturally produce human medicines; they are engineered to become microscopic factories for specific therapeutic proteins. This process uses genetic engineering to alter the cell’s DNA blueprint.
The process begins by identifying the human gene for the desired therapeutic protein, such as a monoclonal antibody. Scientists isolate this gene and insert it into a plasmid, a small, circular piece of DNA that acts as a delivery vehicle. This engineered plasmid is then introduced into CHO cells.
Once inside, the new gene integrates into the CHO cell’s genome, creating a “recombinant” cell line. The cell’s machinery reads this new gene and synthesizes large quantities of the human therapeutic protein. This protein is then secreted into the surrounding liquid culture medium.
Gene insertion is not always efficient, so scientists use selection methods. Along with the therapeutic gene, a “marker gene” that provides resistance to a specific toxin is often inserted. When the culture is exposed to that toxin, only cells that incorporated the new genes survive.
This is followed by cell line development, where scientists screen thousands of cells to identify the single “clone” that is most stable and produces the highest quantity of the protein. This top-performing clone is cultivated and preserved to become the master cell bank for manufacturing a drug.
From Lab to Lifesaving Treatments
The journey from an engineered CHO cell to a medicine involves scaling up production in specialized facilities using bioreactors. These are large, sterile tanks that can hold up to 20,000 liters.
Inside the bioreactor, the selected CHO cell line is provided with an optimized environment. A nutrient-rich liquid called a culture medium supplies everything the cells need to multiply and produce the therapeutic protein. The bioreactor maintains precise control over conditions like temperature, oxygen, and pH for several weeks.
Once protein concentration peaks, the harvesting process begins. The cells are separated from the liquid medium containing the therapeutic protein. This is followed by a multi-step purification process using techniques like chromatography to isolate the desired protein from other cellular components, ensuring the final product is pure and safe.
Medicines produced by CHO cells include most monoclonal antibodies, used to treat many forms of cancer and autoimmune diseases like rheumatoid arthritis. Other products include erythropoietin to treat anemia, blood clotting factors for hemophilia, and enzymes for rare metabolic disorders. The first FDA-approved drug from CHO cells was Activase in 1987, and the technology has been central to the biopharmaceutical industry ever since.