Powering up biologics development using mammalian cell lines

In the realm of biotechnology, use of mammalian cell lines has emerged as a cornerstone in the production of vital biotherapeutics and vaccines. In this article, we dive into the key characteristics of mammalian cell lines that have earned them their critical role in the development of biologics. We examine how expertise and innovative tools in cell line development can be pivotal in advancing a therapy’s path to success.

Mammalian cell lines come into play when a complex protein of interest has been discovered as a potential treatment or cure for a disease. Serving as mini-factories, these cell lines help in production of the protein by integrating genes encoding the protein of interest into host cells. Subsequent steps involve screening and isolating high-yield cell lines, enabling the large-scale expression of the protein for further clinical testing or even eventual use in patients once the therapy is approved.

The power of mammalian cell lines

What are mammalian cell lines?

“Mammalian cell lines consist of immortal cells derived from humans or other mammals,” explained Séverine Fagète, Ph.D., Vice President of Mammalian Cell Line Development at KBI Biopharma, a global contract development and manufacturing organization (CDMO). “These cell lines have been integral to biopharmaceutical research since 1951 and possess the capacity for indefinite cultivation due to continuous divisions.”

Unraveling the reasons behind why mammalian cells have become a biological tool of choice in the production of vaccines and therapeutic proteins, she continued: “Mammalian cells present two key advantages over other cell types such as microbial cells. First is their ability to induce post-translational modifications, enabling expression of complex molecules that fold correctly, giving them appropriate functional structures. Second is their capability to produce proteins bearing human-like glycan structures, which reduce adverse immunogenic responses.”

CHO cell line: A common mammalian cell type

Today, the Chinese hamster ovary (CHO) cell line has emerged as a frontrunner among mammalian cell types, Séverine highlighted: “CHO cells offer unparalleled advantages, including rapid growth, high yield production, reduced susceptibility to viral infections and flexibility in response to process parameters such as pH, temperatures or oxygen levels.”

In fact, their multiple benefits have led CHO cells to support the development of over 70% of approved therapeutic proteins today. Since their introduction in 1986, the biomedical community has amassed over 30 years of expertise in handling CHO cells and understanding their characteristics for bioproduction. This has facilitated the development of a variety of advanced technologies, including engineered expression systems as well as screening methods tailored to CHO cells, allowing scientists to optimize the use of these cell lines.

Partnering right to enhance cell line development

Mammalian cell line development challenges

Today, technological advances combined with added external pressures such as stringent regulatory standards and fierce competition around speed-to-market have made cell line development a competitive phase within biologics development, according to Séverine.

“The emphasis is on high yield and throughput in tight timeframes, without compromising on the quality of the final product. And this is a challenging balance to achieve,” she noted. “Moreover, if the end-product is a complex and versatile molecular format, such as a next generation therapeutic with bispecific constructs that allow a dual mode of action, it only adds to this challenge.”

The need for continuous innovation to meet evolving standards, means that biopharmas often outsource cell line development to domain experts at CDMOs to expedite development timelines and optimize production. 

Choosing the right CDMO for mammalian cell line development

Séverine underscored the importance of selecting the right partner: “A proficient CDMO in the cell line development space provides access to ready, quality-assured and proven expertise. They need to offer an innovative toolkit which should include robust, versatile cell lines – capable of complex protein production with enhanced stability and compatibility with manufacturing processes – along with efficient high-producing single cell selection systems.” 

Highlighting the advantages the right CDMO partner can provide, Séverine elaborated that in KBI Biopharma’s case, their solutions are powered by robust cell lines combined with the latest cutting-edge technology.

KBI Biopharma’s pioneering approach to cell line development

“Our cell line development is based on the SUREtechnology Platform™, powered by Selexis®. This involves a combination of technologies, including the SURE CHO-M Cell Line™, a proprietary cell line,” she shared. “CHO-M cells – derived from CHO K1 cells – are fully sequenced, easy to manipulate and come with a short doubling time enabling a peak biomass accumulation of up to 50 million cells per milliliter, translating into high yield expression levels.”

“We also leverage proprietary epigenetic elements, which are genetic sequences that create a conducive environment when introduced into cell factories, greatly enhancing the stability and the yield of the final protein. Additionally, we employ image- or statistic-based technologies for rapid isolation of high-performance cells created out of this robust set-up, and undertake further product analytics and characterizations as required.” 

KBI Biopharma’s comprehensive approach has enabled them to offer quality-focused, reproducible, time- and cost-effective cell line development services. This has helped several companies streamline their development pathways, facilitating regulatory compliance and accelerated market entry. 

Aligned with trends in next generation therapeutics, the majority of KBI Biopharma’s mammalian cell line development activities now revolve around supporting the development of novel molecular formats such as bispecifics, stated Séverine. “One recent notable success story involved the development of a bispecific format designed for retargeting immune cells to cancer cells – an innovative approach that simultaneously targets cancer cells while recruiting effector cells for their destruction,” she added.

Despite its challenges, cell line development work is extremely rewarding, asserted Séverine. KBI Biopharma has helped clients in reaching significant milestones, including establishing high-yielding cell lines without the need for extensive process development. By leveraging the power of their inherited technologies and their combined expertise, the team at KBI Biopharma takes pride in their commitment to advance innovation, having had the privilege of contributing to bringing 10 biotherapeutics to market to date.

A future of enhanced predictivity

Looking ahead, Séverine envisions a future where agility, innovation and data-driven decision-making will remain center stage in biologics manufacturing.

“Moreover, harnessing technologies such as artificial intelligence will enable greater predictability in mammalian cell line development. Moving forward, this predictivity will play a prominent role in cell line development by helping accelerate high producers identifiction and driving biologic innovation to enhance global health outcomes,” concluded Séverine.

Experts at KBI Biopharma have led over 300 cell line development programs, yielding successful cell lines that have played a vital role in more than 170 drug candidates presently undergoing evaluation in pre-clinical and clinical trials. To learn how you can partner with KBI Biopharma, enabling you to leverage the team’s world-class expertise and their proprietary SUREtechnology Platform™, please visit the company’s website.

Images Courtesy: KBI Biopharma