The Chinese hamster (Cricetulus griseus) was first used as a laboratory animal in China in 1919. Despite being considered an agricultural pest in its native range, this species has cemented its place in life sciences, largely due to the establishment of Chinese Hamster Ovary (CHO) cell lines. CHO cells are central to recombinant protein production, including monoclonal antibodies and other biologics, because they offer the biochemical machinery necessary for producing human-compatible therapeutic proteins.
Why Chinese Hamsters?
Chinese hamsters stand out in research due to their biological advantages, such as a small size, polyestrous reproductive cycle, and relatively short gestation. The species has a low chromosome number, initially estimated at 14 but later confirmed to be 22. This trait, along with other genetic and physiological properties, made Chinese hamsters popular in various biomedical fields. Researchers early on recognized their low susceptibility to spontaneous viral infections, which makes them a valuable model for mutagenic and carcinogenic studies, especially in tissue culture applications.
This species has been used to study susceptibility to several infectious diseases, including bacterial and viral pathogens like Streptococcus spp., mycobacteria, influenza, and rabies. It has also contributed to radiobiological studies, with results indicating that Chinese hamsters are more resistant to radiation than other lab rodents. Notably, they were shown to develop a form of hereditary diabetes mellitus, making them a useful model for diabetes research, given its similarities to human diabetes.
CHO Cell Lines
Initially isolated from Chinese hamster ovaries in the late 1960s, CHO cells offered a stable platform for culturing and manipulating mammalian cells in laboratory conditions. CHO cells allow scientists to express heterologous proteins—proteins not native to the species—and modify them through essential mammalian post-translational processes, including glycosylation, which bacterial or yeast systems cannot replicate.
Glycosylation and other modifications significantly affect protein stability, efficacy, and immunogenicity in humans. Proteins produced in CHO cells tend to exhibit low immunogenicity in humans, making them ideal for therapeutic use. This unique feature has been critical in the development of monoclonal antibodies and related biologics, especially those used to treat cancer, autoimmune diseases, and more.
Since the development of CHO cell lines, recombinant antibody production has become more efficient and scalable, with CHO cells often being modified to express a range of antibody formats, including bispecific antibodies and antibody-drug conjugates. Monoclonal antibodies like trastuzumab (Herceptin), adalimumab (Humira), and others owe their success to CHO-based production systems.
The close physiological similarity between CHO cells and human cells is a major contributor to their success. Antibodies produced in these cells can undergo mammalian-like modifications, which ensures compatibility and safety in human therapeutic applications. By introducing engineered nucleic acids into CHO cells, researchers can manipulate the antibody's structure and binding capabilities.
Manufacturing Advantages of CHO Cells in Biologics
One of the main advantages of using CHO cells in biopharmaceutical manufacturing is the capacity to achieve high cell densities in culture, enabling robust production rates. CHO cells also thrive in a controlled, serum-free culture environment, which reduces the risk of contamination and allows for precise control over growth conditions and production parameters. This predictability is required for regulatory compliance to ensure consistent quality.
CHO cells are now engineered for optimized productivity and cell line stability. Advances in genetic engineering, such as gene amplification techniques and CRISPR/Cas9, have further increased the expression rates of antibodies in these cells.
References:
Miedel, E. L., & Hankenson, F. C. (2015). Biology and Diseases of Hamsters. Laboratory Animal Medicine (Third Edition), 209-245. https://doi.org/10.1016/B978-0-12-409527-4.00005-5
