Chinese hamster ovaries, or CHOs, have played, and continue to play, a pivotal role in the development of lifesaving drugs. They’re a cornerstone of modern biopharmaceuticals, providing the foundation for the development of therapeutic proteins and monoclonal antibodies through a process known as cell line development. This article explores the origin, development, and application of CHOs, with a focus on their use by contract development and manufacturing organizations (CDMOs) such as Samsung Biologics, whose S-CHOice® system utilizes CHO technology.

What Is a Cell Line?

A cell line refers to a population of cells derived from a single cell and cultivated in a laboratory. These cells are genetically identical and can proliferate indefinitely under controlled conditions in vitro, meaning outside of a living organism. Cell line development, or the continuation of these cell lines, is vital for studying biological processes, producing therapeutic proteins, and developing effective biologics.

The Emergence of CHOs

The story of CHOs begins in the 1950s, when they were first isolated from the ovaries of Chinese hamsters. Theodore Puck and his colleagues at the University of Colorado were the pioneers in this field, recognizing the potential of these cells for in vitro studies.

In 1962, Harry Eagle further refined the cultivation techniques, leading to the development of the first CHO cell lines. These cells were found to be robust, easy to manipulate, and capable of producing proteins in large quantities. Their use quickly spread across the scientific community.

In 1977, scientists at Genentech, led by Roberto Crea and Keiichi Itakura, successfully used CHO cells to produce human insulin. This was a landmark achievement, demonstrating the potential of CHOs for therapeutic applications.

CHOs have now become a mainstay in the biopharmaceutical industry. Their use has expanded to include the production of a wide range of products, from vaccines to targeted cancer therapies.

Obtaining and Developing CHOs in Vitro

CHOs were originally obtained from the ovaries of Chinese hamsters, a small rodent native to northern China and Mongolia.

However, once isolated, CHO cells are capable of proliferating in vitro, and there’s no longer the need for extraction from a living organism. Cell line development involves cultivating cells in a nutrient-rich medium that supports their growth and division. Genetic engineering techniques can be applied to modify the cells, enabling them to produce specific proteins or antibodies. This process often involves the insertion of foreign genes into the CHO cells, equipping them with the ability to synthesize the desired products.

CHOs in the Biopharmaceutical Industry

The biopharmaceutical industry has embraced CHOs for their ability to produce complex proteins that are often difficult to synthesize using other methods. Cell line development of CHO cells is used to manufacture a wide range of products, from insulin to cancer-fighting antibodies.

CDMOs have played a significant role in this process. These organizations provide specialized services to biopharmaceutical companies, including the development and manufacturing of products using CHO cell lines. By leveraging the versatility of CHOs, CDMOs can offer cost-effective solutions, accelerating the path from late-stage drug discovery, to Investigational New Drug filing, and ultimately to commercialization.

Samsung Biologics’ S-CHOice Solution

Samsung Biologics S-CHOice®platform, announced in 2020, can streamline the efficiency of CHO cell line development. Utilizing a specialized system known as GS (glutamine synthetase) knock-out, it removes GS from the cells to facilitate manipulation and development. This platform has the ability to achieve titers above 7 g/L for standard antibodies, with 90% of cells remaining stable after over 20 days of development.

S-CHOice® utilizes the CHO-K1 cell line, which was derived in the early 1960s. It was one of the first CHO cell lines to be developed and has since become a standard tool in various scientific applications. CHO-K1 cells are known for their robust growth and adaptability. They can be grown in both adherent and suspension cultures, making them versatile for different laboratory settings. The cells are epithelial-like in morphology and have a stable karyotype, which contributes to their consistent performance.

CHO-K1 has been the subject of extensive genetic manipulation. Its genome has been sequenced, providing valuable insights into its genetic makeup and facilitating targeted modifications.

Alongside S-CHOice®, Samsung Biologics has integrated the Beacon® system, a tool designed for precise single cell cloning. This fully automated system can screen an impressive 5,000 individual cells to identify the best producers. The Beacon®platform’s ability to quickly and accurately isolate productive cell lines is a game changer in the industry, accelerating the drug development process.

An Invaluable Biopharmaceutical Asset

CHOs have come a long way from their humble beginnings in a laboratory in Colorado. Today, they’re an indispensable tool in the biopharmaceutical industry, driving innovation and saving lives. Their development, cultivation, and application are a testament to human ingenuity and the relentless pursuit of scientific advancement.

Through the use of CHO cell lines, researchers and CDMOs alike are unlocking new possibilities in medicine, making therapies more accessible and effective. The story of CHOs is a vivid illustration of how a seemingly obscure biological entity can become a linchpin in the quest for better health and well-being.

By Manali