The Protein Science Facility, Testa Center, and STUNS Life Science had a joint presentation on the 29th of November 2021. How can Karolinska Institutet utilize these support organizations and their resources for large-scale biomolecule production?!
Tomas Nyman, Head of the Protein Science Facility (PSF) Karolinska Institutet / SciLifeLab.
On PSF services.
General agreement between Karolinska Institutet and the Testa Center.
Angelica Loskog’s area of research is cancer, specifically, chimeric antigen receptor (CAR) T-cells, which she began to study as a postdoc at the world’s largest cell and gene therapy center, the Baylor College of Medicine in Houston, Texas. Today she is CEO of Uppsala-based Lokon Pharma, which is attempting to combat tumors with the help of oncolytic adenoviruses. Their first gene therapy candidate, known as LOAd703, is already being clinically tested and evaluated for several different cancers; pancreatic, ovarian, colorectal, biliary tract and melanoma.
Now Lokon Pharma has managed to scale up its manufacturing process and demonstrated that it works reliably. They are more than happy with the results gained after just nine weeks at Testa Center.
– We have achieved fantastic results in a very short time. We spoke directly with all the expertise at Testa Center, utilizing their broad know-how as a filter in direct discussions with people familiar with our own company’s specific project needs. This paved the way for success. We have, for example, being able to run tests relevant to just our particular product.
Angelica Loskog, CEO at Lokon Pharma.
Together with Testa Center staff, Lokon Pharma has ‘set the stage’ and obtained a good overview of the manufacturing process, thereby becoming experts in their product. It’s cool, comments Angelica, emphasizing that the time spent at Testa Center was particularly valuable in securing a robust CMC (Chemistry, Manufacturing and Controls) road map for their process.
– We can now state with certainty what the CMC should look like and that’s a fundamental basis for market approval. In all the excitement of collecting clinical data, it can be easy to forget that you still need effective and reproducible products!
Angelica also emphasizes the contribution of Lokon Pharma’s own CMC expert, Sara Häggblad. Her knowledge and experience have also been crucial for the success of the project. Before Lokon Pharma, Sara was an adenovirus expert within CMC at Cytiva. She now believes that their newfound success at Testa Center can provide a better understanding of this type of adenovirus product – specifically, that it can be produced reliably at a large scale.
Previously, process development of this type has been driven by big international players – the industry’s dragons – but this ‘homegrown’ success story shows that neither large nor specialist facilities are essential. Angelica also believes that it will be easier for Lokon Pharma to engage with manufacturers now that they know their process inside out. In other words, it will be easier to guide production partners correctly and that, in turn, will have a great impact on the result.
– When you understand exactly what to do. Uncertainty disappears. Having our process verified at Testa Center is pure risk minimization. It’s also a seal of quality. Testa Center is an incredibly important bridge that leads from academia straight into industry. Its value cannot be overstated. Cell and gene therapy has always been strongly grounded in academia, but now I firmly believe in a future shift towards large-scale manufacture, broader application in cancer treatment, and greater patient benefits, concludes Angelica Loskog.
The International Genetically Engineered Machine (iGEM) competition is an annual and worldwide synthetic biology competition. The event attracts about 6 000 participants who are undergraduate university students, as well as high school and graduate students. Uppsala University has a strong history in the education of biology. Students from Uppsala have also been participating in the competition at least since 2009.
The IGEM competition “is an opportunity for the team to push the boundaries of synthetic biology by tackling everyday issues facing the world. Multidisciplinary teams work together to design, build, test, and measure a system of their own design using interchangeable biological parts and standard molecular biology techniques.” (source: igem.org)
There are several different Medals and Special Prizes to compete for. To win, the teams have to fulfill several demanding criteria. All teams have to present their projects to the entire iGEM community to compete for the medals, awards, and prizes. The winners are then announced during an Awards Ceremony, which is the culmination of the Giant Jamboree.
The Uppsala IGEM Assiciation and team
The Uppsala IGEM Association has a team for 2021 that consists of nineteen highly motivated students with various backgrounds and bio-related educations.
The team looks to “optimize the growth factors used in serum-free media to support the growth of cultivated meat. Given that one of the largest hurdles of the production is upscaling, we will be engineering one of the two growth factors, FGF-2, holding the cost high and are needed in the culture media.”
Their goal is to test for the optimization of bovine FGF2 in a few different ways;
Improving the thermal stability to lower the degradation rate in media.
Improving the binding affinity to receptor (FGFR2) through point mutations.
Combine FGF-1 and FGF-2 to create a chimeric protein FGF-C for bovine. Done to maintain mitogenic activity, primarily through preventing trypsin degradation. By this, increasing solubility, hence expression.
They aim to increase the yield of the protein, hence lowering the production costs. Hopefull for expressing the modified FGF2 proteins, the plan is to purify and upscale the protein in bioreactors to test the media.
A very warm welcome to the Testa Center to all the participants of the Uppsala University team! The Testa Center staff all hope that you will find your stay useful. We are certain that you learn a lot. We keep our fingers crossed that you will succeed with your ambitious plans. Good luck in the competition!