The biopharmaceutical industry is witnessing remarkable growth with the development of innovative protein-based therapies. Behind this revolution stands a silent yet powerful champion: Chinese Hamster Ovary (CHO) cells. These cells have become the gold standard in biopharmaceutical production, playing a vital role in manufacturing monoclonal antibodies, vaccines, and hormones. Their unparalleled scalability, productivity, and safety make CHO cells the workhorse of the biopharma industry.

The Legacy of CHO Cells

CHO cells have a rich history that traces back to the 1950s when Theodore Puck, a pioneering biologist, established the first stable CHO cell line known as CHO-K1. This breakthrough marked a turning point, leading to their widespread adoption in mammalian cell culture. However, the true reign of CHO cells began in the 1970s with the surge of protein therapeutics. What sets CHO cells apart from bacteria is their ability to perform complex post-translational modifications (PTMs), critical for protein functionality and biocompatibility. This unique capability, combined with their adaptability to large-scale production, propelled them to the forefront of biopharmaceutical manufacturing.

CHO Cells in Biologics and Vaccine Manufacturing

During biologics production, CHO cells serve as the host cells for the expression of recombinant proteins. Through genetic engineering, the gene of interest is introduced into CHO cells, which then produce the desired protein in large quantities12. CHO cells are particularly well-suited for this process due to their high productivity, scalability, and ability to perform complex post-translational modifications (PTMs). These PTMs are essential for the functionality and biocompatibility of recombinant proteins.

Vaccine Development Workflow: In vaccine development, CHO cells are instrumental in producing recombinant subunit vaccines. The process begins with the genetic engineering of CHO cells to express specific antigens of interest. These antigens, typically derived from pathogenic proteins, stimulate immune responses in individuals. CHO cells are then cultivated in large-scale bioreactors, allowing for robust and efficient production of antigens. Subsequently, the produced antigens are purified, ensuring high yield and quality. Purified antigens serve as active components in vaccine formulations, ultimately driving an immune response in recipients.

Biologics Development Workflow: CHO cells also play a pivotal role in the development of biologics. Through genetic engineering, CHO cells are transformed to express recombinant proteins of interest. This unique feature of CHO cells enables the expression of proteins with complex post-translational modifications (PTMs), crucial for maintaining protein functionality and biocompatibility. CHO cells proliferate and produce these recombinant proteins, often achieving high yields. The harvested proteins undergo downstream purification processes to ensure their safety, efficacy, and desirable qualities.

The Advantages of CHO Cells

CHO cells dominate the field of protein expression due to their multifaceted advantages, making them the preferred platform for researchers:

Adaptable Culture: CHO cells thrive both in suspension and adherent cultures, seamlessly adapting to Good Manufacturing Practice (GMP) procedures. Their versatility makes them ideal for efficient and cost-effective production in large-scale bioreactors.

Unparalleled Productivity: CHO cells can generate high yields of recombinant proteins, often exceeding 3-10 grams per liter of culture. Ongoing genetic optimization efforts further enhance this exceptional productivity.

Defined Culture Conditions: CHO cells have the ability to adapt to serum-free, animal-free, and protein-free media, ensuring improved product safety and stability profiles. This is crucial for developing biopharmaceuticals with minimal contamination risk and enhanced efficacy.

Diverse Selection Systems: Scientists employ selection systems, such as DHFR- and GS-deficiency, to identify high-producing clones effortlessly. These systems significantly expedite the development of stable and efficient production lines.

Biosimilar and Human-Identical Products: CHO cells’ capacity for PTMs enables the production of proteins with biosimilar or even human-identical structures. This guarantees high activity, biocompatibility, and minimized immunogenicity in the final therapeutic product.

Genetic Engineering Amenability: CHO cells readily lend themselves to various genetic engineering techniques, such as gene introduction, knock-out, and silencing. This empowers researchers to optimize protein expression, improve product characteristics, and develop novel biopharmaceuticals.

FDA-Approved Platform: CHO-derived biopharmaceuticals have well-established safety and efficacy records. With nearly 50 FDA-approved biotherapeutics produced using CHO cells, their extensive use and reliability in the industry are evident.

Low Risk of Viral Contamination: Being of hamster origin, CHO cells are less susceptible to human viruses. This significantly mitigates the risk of viral contamination during production, ensuring the safety of the final therapeutic product.

Research Forward

Continued advancements in cell line engineering and bioprocess development predict the enduring dominance of CHO cells in the biopharmaceutical landscape. High-throughput screening platforms, optimization algorithms driven by artificial intelligence, and novel protein expression systems are expected to further enhance the productivity and efficiency of CHO-based production processes.

Moreover, the burgeoning demand for personalized medicine and targeted therapies spurs the development of next-generation CHO cell lines with enhanced capabilities. This includes engineering cells to have glycosylation patterns, improved secretory pathways, and the ability to produce complex multi-protein therapeutics. As scientists delve deeper into the secrets of CHO cells and unlock their full potential, the future of biopharmaceutical development promises to be brighter and more impactful than ever before.

References

Wurm, F. M. (2013). CHO cell lines in biotechnology for biopharmaceutical production. Animal cell culture methods, 1-28.

Lewis, N. E., et al. (2013). Genomic landscapes of Chinese hamster ovary cell lines used in production of biopharmaceuticals. Nature biotechnology, 31(8), 757-765.

Shukla, A. A., & Thommes, J. (2010). Recent advances in large-scale production of monoclonal antibodies and related proteins. Trends in biotechnology, 28(5), 253.

Technologynetworks.com. (2023). Advances in CHO Cell Line Development for Biotherapeutics. Retrieved from www.technologynetworks.com/biopharma/articles/advances-in-cho-cell-line-development-for-biotherapeutics-381065

NCBI. (2016). Human cell lines for biopharmaceutical manufacturing: history, status.. Retrieved from www.ncbi.nlm.nih.gov/pmc/articles/PMC5152558/

NCBI. (2021). Platforms for Production of Protein-Based Vaccines: From Classical to… Retrieved from www.ncbi.nlm.nih.gov/pmc/articles/PMC8394948/

Zhu, J. (2012). Mammalian cell protein expression for biopharmaceutical production. Biotechnology Advances, 30(5), 1158-1170. Link to the article

Lim, S., Luan, X., Lim, S. M., Gadkari, S., & Poon, H. F. (2015). Chinese hamster ovary (CHO) cells: production and perspectives. In CHO cells: Methods and protocols (pp. 1-15). Springer, New York, NY. Link to the book chapter

Wang, J., Ritter, N., Chung, C. C., Frazer, L., & Chan, D. Y. (2021). Chinese hamster ovary (CHO) cells as hosts for the production of biopharmaceuticals. Medicina, 57(1), 35. Link to the article

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