CHO cell research at DTU Biosustain and National Biologics Facility

DTU expands research and collaboration on cell cultures

Friday 12 Feb 21

Contact

Bjarke Bak Christensen
Head of Department
DTU Bioengineering
+45 30 66 42 33

Contact

Bjørn Gunnar Voldborg
Director Cell Line and Protein Production Facility
DTU Bioengineering
+45 21 12 61 91

Contact

Christian Mostrup

Senior Programme Lead

Novo Nordic Foundation

+45 3067 4805

cims@novo.dk

CHO Cells

Proteins produced in hamster cells (CHO cells) have been used since the 1980s. The cells are relatively easy to cultivate, and their genes can be modified so that they can be utilized to produce, for example, cancer medicine, haemophilia medicine, psoriasis medicine, and hormones when they are developed for new biomedical purposes. The wide range of applications of CHO cells has meant that pharmaceuticals produced from CHO cells are more easily approved by the authorities. In addition, CHO cells have been shown to be safe as a production host—unlike human cells—which are often hard to cultivate and which are more vulnerable to infection with human viruses.

During the past three decades, several protein biological substances have been approved by the medicines authorities, and the vast majority of substances have been developed from CHO cells. Based on a single year like 2018, seven of the top ten best-selling pharmaceuticals were based on proteins, and all except one were produced based on CHO cells.

In the past seven years, DTU’s CHO programme has been the key to the development of CHO cell line technology into an engineering science. The data, tools, and approaches behind the development of The Novo Nordisk Foundation Center for Biosustainability’s CHO programme have fundamentally changed both the scope and ambitions of the projects based on cell technology that can be pursued in academia and in the biotechnology industry.
Danish research into cell cultures and the development of proteins for biological pharmaceuticals—including for cancer treatment—is strengthened with new unit at DTU.

DTU is increasing its activities in research and education in the development of cell cultures for production of proteins from hamster cells (CHO cells) for use in biological pharmaceuticals, which are in great demand by companies in the pharmaceutical industry.

The increase in activities in this field is funded by an initial grant of DKK 20 million from the Novo Nordisk Foundation. The grant makes it possible to establish a research and teaching environment in Cell Culture Engineering at international elite level and to increase the focus on the establishment of industrial collaborations in this field. The research environment will be based on the existing environment in The Novo Nordisk Foundation Center for Biosustainability (CFB), which will be transferred and extended to a National Biologics Facility (NBF) at DTU Bioengineering.

“DTU sees great prospects in integrating cell culture technologies into our research and study programmes. DTU already has several internationally leading programmes in the development of biological pharmaceuticals. When we combine these activities with CHO cell research in a new National Biologics Facility, we have the academic, professional, and research capacity to establish a brand-new international research and education environment,” says Bjarke Bak Christensen, Head of DTU Bioengineering.

Claus Felby, Senior Vice President of the Novo Nordisk Foundation, welcomes the establishment of the National Biologics Facility.

“The strong focus on bringing the impressive results of the research into CHO cells to the pharmaceutical industry and strengthening the teaching activities is important if we’re to continue to develop Denmark’s positions of strength in biotechnology,” says Claus Felby.

International leader

Research into cell cultures based on hamster cells—CHO cells—for the production of proteins was established at DTU in 2012. In just eight years, the research team at CFB has succeeded in becoming an international leader in the development of new cell lines that can be used to produce new and better biological pharmaceuticals for a large number of diseases, including cancer and other diseases for which there are currently no optimal treatment methods. One example is the lifelong treatment with Alpha-1 antitrypsin administered to patients who lack the natural protein. They are treated weekly with large doses of Alpha-1 antitrypsin—extracted from donor blood plasma—but with the newly-developed CHO cells from DTU, the necessary Alpha-1 antitrypsin can be produced in CHO cells instead.

CHO cells are most often used to produce pharmaceuticals containing large complex proteins. The challenge is that the proteins do not always completely match human proteins. The reason for this is that the cell adds some antenna-like sugar groups—so-called glycans—to the protein. And hamster cell glycans are not identical to human cell glycans. Most recently, researchers from CFB have published positive results from trials using CHO cells made at DTU to produce various glycan variants of, for example, the substance Epo— which is known from blood doping in cycling—but which is also used to treat anaemia. The researchers discovered that CHO cells could be used for biological production of protein variants if they modified genes that were involved in the structure of glycans on the protein. Examples of this were published in the journal Metabolic Engineering in 2020.

Companies receive help to develop proteins

In addition to being involved in a number of research breakthroughs in the development of potential pharmaceuticals, CFB has produced graduates—laboratory technicians, MSc and PhD students, postdocs and senior researchers—who now work in this field and disseminate the latest research in the companies. In the first year, this is supported through the project’s principal focus on establishing industrial collaborations.

“We want to use the research facilities to help small and medium-sized enterprises in their work to produce proteins for research use and development. The idea is that they’re to be able to draw on our expertise, facilities, and educational environment to produce the proteins they need in their preclinical research and development. Correspondingly, we’re to produce proteins that researchers and students can work with in the academic environment,” says Bjørn Voldborg, who becomes Head of NBF.

The establishment of NBF is organized as a public-private partnership. Academic profiles such as Professors Lars Nielsen, Thomas Andresen, Steffen Goletz, and Andreas Laustsen will help develop the research and teaching environment at MSc, postgraduate, and continuing education levels.

Bjørn Voldborg sees NBF as the foundation for major initiatives in the discovery of new pharmaceuticals, pharmaceutical development, and the production of protein-based medicines, where today such holistic initiatives are not prioritized in Denmark.