The range of indications for plasma proteins is constantly growing!

CEVEC Pharmaceuticals GmbH is focused on the production of difficult to produce proteins using its cell-based expression platforms CAP-Go and CAP-GT.

Translation of an Interview with Dr. Nicole Faust, Chief Scientific Officer, CEVEC
Plattform Life Sciences, Biotechnologie 2017, 19. Jahrgang, September 2017, pp 98-99

Plattform Life Sciences: Dr. Faust, what is special about CEVEC’s cell-based expression platforms CAP-Go and CAP-GT?

Faust: CAP-Go is used in the expression and production of recombinant proteins that are involved, for example, in cancer therapies. Probably the best-known proteins of this type that are routinely produced by most of our competitors are antibodies. However, with our cell lines we prefer to focus on proteins that are difficult to produce, such as plasma proteins, which either can’t be produced or are only produced in insufficient quantities and quality using existing expression systems.

CAP-GT is optimized for the scalable production of viral gene therapy vectors that are used in gene therapy applications and allow for targeted introduction of specific genes into diseased cells or, in the case of cancer, into tumor cells.

Our platform is developed specifically for each respective application. The cell lines used for the production of proteins and vectors are of human origin and are constantly being expanded and optimized. Today, CAP technology comprises an entire range of cell lines that can produce an extremely wide variety of proteins and viral vectors of optimum quality.

One important area of application for CAP is in the production of viral vectors for gene therapy – what are the advantages of your CAP-GT technology over other expression systems?

Faust: One important advantage is scalability. A challenge in gene therapy vector manufacturing is the production of larger batches. Current production systems are normally based on HEK 293 cells, a cell line that grows adherently, meaning the cells grow as monolayer on an artificial substrate, which naturally limits scalability. Additionally, the cells need a specific high protein serum in order to grow, which regulatory authorities do not like as it constitutes a greater risk of contamination.

The cell lines of our CAP-GT platform are suspension cell lines. These cells reproduce in a serum-free medium that allows for efficient and secure production and problem-free scalability. Moreover, the cell density of our suspension cell line is very high compared to cells growing adherently, which is ultimately reflected in a much higher yield.

The most common method currently employed in the production of gene therapy vectors by means of cell lines is transient transfection. In this method, the respective virus DNA needs to be introduced into the cells before each production run which is very expensive and difficult to accomplish on a large scale. As a result, the capabilities of transient transfection will eventually reach their limits with advances in gene therapy. At CEVEC, we have already made considerable progress in the development of stable cell lines that can produce gene therapy vectors without further transfection.

“Theoretically, our CAP-GT platform can be applied to all gene therapy diseases.”

What are the main indications, the products and vectors produced on these platforms are used in?

Faust: With CAP-Go we are currently focusing on the blood coagulation disease, hemophilia. The blood coagulation factors currently in use are frequently still purified from human blood plasma. However, more and more producers are moving towards a recombinant manufacturing of these factors, as only a recombinant production provides the opportunity, for example, to improve the therapeutic effect by modifying the structure and/or glycosylation. Conventional CHO (Chinese hamster ovary) cells run up against limits here, as they hardly can produce complex molecules. We are currently working on various projects, where we are developing and optimizing production processes that will allow us to produce blood coagulation factors or other proteins using our CAP-Go cell lines on an industrial scale.

Another disorder that we are addressing is hereditary angioedema, a genetic defect involving chronically recurring swelling of the skin, mucous membranes or internal organs. To the best of our knowledge, our CAP-Go platform is the only platform that can produce the necessary plasma protein, C1-esterase inhibitor, in sufficient quality on a recombinant basis.

Theoretically, our CAP-GT platform can be applied to all gene therapy diseases. Currently it is being used primarily on rare diseases.

Are there any other potential applications for your production platforms aside from recombinant plasma proteins and gene therapy vectors?

Faust: Our CAP cells can also be applied to other production processes, such as in the field of vaccinations. There are several projects in this area in which the CAP cell lines are used to produce vaccines based on viruses. In this regard, one project worth mentioning is our collaboration with U.S. company NewLink Genetics. They have licensed our CAP platform for development of a Zika vaccine.

Recently, we concluded a cooperation agreement with a leading European pharmaceutical company for the development, production and marketing of veterinary vaccines using our CAP-GO platform. In addition, we can also serve new areas such as exosomes for use in diagnostics and, today increasingly, therapies.

What market potential do you see in the future for CEVEC technology?

Faust: At present, we are focusing on what is currently still a niche market, although we see very good growth potential, as is the case with recombinant plasma proteins. Producers in this market are beginning to change their minds, and no longer purifying their proteins from human plasma. Going forward, those aiming to make improved molecules will have to produce them on a recombinant basis. Moreover, plasma resources will hardly suffice to cover future needs as the range of new indications for plasma proteins is constantly growing. In the field of gene therapy we will have to wait and see what future market development brings.

Dr. Faust, thank you for this interesting discussion.

The interview was conducted by Holger Garbs.

ABOUT THE INTERVIEWER

Prior to joining CEVEC as Chief Scientific Officer, Dr. Nicole Faust held various management positions at Artemis/Taconic Biosciences, amaxa and Lonza in the fields of pharmaceutical models, gene transfer and protein production and gene therapy.

Contact:

CEVEC Pharmaceuticals GmbH
Dr. Nicole Faust
Chief Scientific Officer
Phone: +49 221 460 20 800
Email: info@cevec.com