Interview: These Cell Lines Give Biopharmaceutical Development a Boost

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The search for novel biopharmaceutical agents is an ongoing challenge in pharma research and drug development. The cells that express such therapeutics play a crucial role in this search. However, researchers often face a number of problems with cell lines, including productivity, quality, robustness, and challenges when scaling-up.

We have caught up with Dr. Ulrich Kettling, Vice President of Business Development at the biotech company CEVEC Pharmaceuticals. The team at CEVEC has developed a technology that allows for the development and production of innovative biopharmaceuticals, such as complex therapeutic proteins and gene therapy vectors.

Dr. Kettling, what is CEVEC doing and which industries are you targeting?

Ulrich Kettling, cell lines, cell line development, Cevec, glycosylation, vaccines, gene therapy vectors
Dr. Ulrich Kettling, VP Business Development at CEVEC 

CEVEC’s core competence is the screening and development of cell lines to produce high-end biopharmaceuticals, such as complex fusion proteins, highly glycosylated plasma proteins or viral particles.

Our customers range from small to large biotech and pharma companies, including basically any company with an R&D focus on novel forms of medications and treatment, such as cell and gene therapies, immunotherapies, tumor vaccines, as well as protein therapeutics.

We help our customers to gain access to such novel biopharmaceuticals, to test them and to produce them. From small amounts for screening and evaluation, up to large quantities for clinical trials and commercialization. Complex molecules are often not accessible via classical cell culture methods, that’s where our CAP® technology comes into play and that’s where we offer unique solutions.

What is the CAP® Technology and how has it developed over time?

CEVEC’s CAP® Technology is based on unique cell lines, which have been isolated and developed as a production system for biotherapeutics. Initially developed for the production of vaccines, viruses and complex glycosylated proteins, our focus today is shifting towards gene therapy vectors.

The CAP cells are unique in their production potential. They are extremely robust cells and grow to high cell densities in suspension culture using standard bioreactors. They can also be easily scaled-up to industrial volumes. In addition, we genetically modify and engineer these cell lines, and fine-tune them according to the project’s needs. As the cells are of human origin, resulting products are very similar and often identical to proteins made by the human body.

Over the years, the CEVEC team has developed a comprehensive portfolio of different production and propagation of cell lines for varying applications. Starting with the isolation and optimization of the cells, a great effort has been made to document the development of the CAP cell lines.

Thus, the complete and detailed history of the cell line is known, including all materials the cells have been in contact with. This simplifies the regulatory process significantly, and we have received very positive feedback from the regulatory authorities. We have also compiled a biological master file with the FDA, which our clients use as a reference.

The CAP®Go technology focuses on the glyco-optimization of proteins. What is the potential of these cell lines for the development of biopharmaceuticals?

cell lines, cell line development, Cevec, glycosylation, vaccines, gene therapy vectors, CAP-Go
The CAP®Go technology focuses on the glyco-optimization of proteins

Almost all proteins produced in the human body, and in particular those that are secreted into the human plasma, are post-translationally modified. The most important posttranslational modification is glycosylation, a process in which sugar moieties are attached to the secreted proteins.

These sugar moieties are responsible for a number of different factors, such as stability, solubility, and plasma half-life, in other words, pharmacokinetics. Researchers are often interested in drugs that can circulate longer in the plasma. This is particularly important if these biopharmaceuticals are made to replace proteins or other factors that the human body is deficient of, as is often the case in genetic diseases.

CEVEC’s CAP®Go expression platform comprises a comprehensive portfolio of glyco-optimized human suspension cell lines that differ in their glycosylation capabilities and allow for the recombinant production of a variety of complex and glycosylated proteins, including plasma proteins, coagulation factors, and cytokines.


cell lines, cell line development, Cevec, glycosylation, vaccines, gene therapy vectors, CAP-Go
“Depending on the selected CAP®Go cell line, the expressed protein shows different glycosylation patterns“


Depending on the selected CAP®Go cell line, the expressed protein shows different glycosylation patterns. Therapeutic proteins expressed in conventional expression systems, such as CHO or HEK cells, by contrast, often do not match the glycosylation and pharmacokinetic profiles of their plasma-purified counterparts. The CAP®Go technology provides a unique and highly economical solution for this.

The second technology CEVEC is working on is the CAP®GT technology for the production of viral vectors. How does this technology change the development of biopharmaceuticals?

cell lines, cell line development, Cevec, glycosylation, vaccines, gene therapy vectors
“The ‘GT’ in CAP®GT stands for gene therapy. This platform comprises a group of cell lines for the production of viral vectors.”

The CAP®GT technology is the most recent addition to our offering. The “GT” in CAP®GT stands for gene therapy. This platform comprises a group of cell lines for the production of viral vectors. Viral vectors are complex particles that transport a gene of interest to a specific cell type or tissue. The viral particles themselves are engineered to do this without being infectious or harmful.

The viral vector is the Achilles heel of gene therapy – it is crucial for every gene therapy to deliver the gene of interest to the targeted cells. However, with an increasing number of gene therapies under development for systemic application, it is becoming increasingly challenging to manufacture sufficient amounts of vectors at high quality. This limits treatment options for common indications, such as Alzheimer’s or Parkinson’s disease.

This challenge, also referred to as the production gap in gene therapy, is what we target with our CAP®GT technology. We cover all common viral vectors currently in use, including adeno-associated viral (AAV), lentiviral, and adenoviral vectors.

“The viral vector is like the Achilles heel of gene therapy. We are making the manufacturing of such vectors as easy as the production of monoclonal antibodies.”

CEVEC has developed a stable production system for producing AAV vectors in cell culture, similar to monoclonal antibodies or other proteins. Whereas traditional methods for vector production require multiple, transient transfections of cell lines – a process that is difficult to reproduce under industrial conditions and can hardly be scaled-up – the CAP® technology is based on stable cells that produce viral vectors upon induction.

We are the first and only company to offer such a solution, making the production of AAV vectors as easy as the production of monoclonal antibodies. The principle of the stable production approach developed by CEVEC is based on the fact that the genome of the CAP cell already contains all the information needed for the viral vector production.

When the cells’ growth reaches the desired production volume, they are switched on and produce the viral vector. At the moment we are testing and upscaling this technology extensively in-house and in collaboration with leading companies in the gene therapy sector. We – and our partners -believe that this technology has the potential to completely change the production landscape for viral vectors.

Are there any novel forms of application for the CAP® Technology?

cell lines, cell line development, Cevec, glycosylation, vaccines, gene therapy vectors
“Exosomes are small, subcellular vesicles which are released by human cells. They can be used as therapeutic vehicles as they can be made, for example, to carry signaling molecules”

While we are focusing on the activities described above, there are attractive opportunities for our CAP® technology in other areas as well. For example, our cell lines are also well suited for the production of adenoviral vectors used as oncolytic viruses, vaccines based on antigen-presenting vectors, and for virus-like particles (VLPs).

A more recent application we are looking into is the use of exosomes as a novel therapeutic option. Exosomes are small, subcellular vesicles, which are released by human cells. They can be used as therapeutic vehicles as they can be made, for example, to carry signaling molecules. First results have shown that CAP cells are excellent exosome producers and together with our partners, who are investigating the therapeutic use of exosomes, we have just started to explore their full potential.

Can you describe one or two examples in which the CAP® Technology has successfully supported the development of biopharmaceuticals?

Plasma proteins are an extremely important example here. Traditionally, they are purified from human plasma, but this has major disadvantages. For example, there is a risk of potential contamination or supply chain issues. With the help of our CAP®Go expression system, we are able to produce plasma proteins of the highest quality and sufficient volumes.

Moreover, we are able to optimize and improve the proteins in terms of efficiency, pharmacokinetic properties, and fewer side effects. We are working with major companies in this sector, including CSL Ltd. and Biotest. Important indications include the treatment of hereditary angioedema (HAE) and hemophilia.

Laminins are another example. Laminins are amongst the most complex proteins. They are part of the extracellular matrix, consist of three chains, are heavily glycosylated and difficult to produce. With our CAP®Go technology, we have been successful in the production of different laminins with high productivity, and we plan to continue our research in this area.

We are working together with the Swedish biotech company BioLamina, to make these laminins accessible as cell therapy reagents. In cellular research, laminins can be used to provide cell culture matrices that allow researchers to imitate the natural, cell-specific cell-matrix interaction in vitro for a variety of applications, including reliable expansion of pluripotent cells and differentiation and maintenance of specialized cell types. This enables new cellular research and consequently, new therapies.

Let’s take a peek into the future. What is your vision for CEVEC?

With the Pharma industry studying more and more complex therapeutics, including gene and cell therapies, new solutions for expression and manufacturing technologies are needed. CEVEC is very well positioned in this area. We are the partner of choice for glycosylation-engineered human cell lines.

We enable the production of complex, human fusion proteins when other cell lines and expression systems are at their limit, and we are a pioneer in large scale vector manufacturing.

With our CAP®GT platform, we overcome the production gap and open the way for the broad use of modern therapies in a wide range of medical indications. Our vision is that CEVEC’s technology will be a key element for the development and therapeutic success of these exciting new and emerging options to treat patients worldwide.

Working in gene therapy or protein production? Want to learn more about CEVEC’s CAP® Technology? Get in touch with the experts here!


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