Unravelling the mysteries of cancer cells

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A new instrument in Oslo Cancer Cluster Incubator will help researchers to learn how cells function so novel cancer treatments can be developed.

The instrument Seahorse was recently donated by Radiumhospitalets Legater to Oslo University Hospital’s Department for Cell Therapy and will be available for all researchers in Oslo Cancer Cluster Incubator.

“The Department of Cell Therapy is in the international forefront in their field of research. Radiumhospitalets Legater is proud to support their endeavor with this important instrument,” says Jan Vincents Johannessen, Head of Radiumhospitalets Legater.

The instrument can make important measurements inside cells to understand the mechanisms of many diseases, including cancer. The data is collected from live cells in real-time, which will give researchers novel insights into cell metabolism.

“A Seahorse instrument measures the metabolism of cells, their respiration and energy production in real time and at high throughput,” said Dr. Else Marit Inderberg, senior scientist at the Department of Cell Therapy, Oslo University Hospital.

Metabolic reprogramming is emerging as a critical target in therapeutic intervention, for example in the development of new cancer treatments, which is why this instrument is so important for academics and companies in the cancer field.

“Metabolism plays a central part in the evolution of cancer cells and also in the efficacy of immune cells that infiltrates tumour cells. A tool that permits measuring the different metabolism modalities of both cancer cells and immune cells is an invaluable asset in the development of new therapeutic approaches,” Dr. Inderberg continued. “We will use the instrument to both assess the cancer cells as target cells and to optimize our immune cells used in therapy. This may help to provide clues about why some patients in clinical trials respond to different types of treatments and some do not.”

The instrument is placed in one of the laboratories in Oslo Cancer Cluster Incubator, where both academic researchers and researchers from private companies can access it as they develop new cancer treatments. Oslo Cancer Cluster Incubator, by laboratory manager Janne Nestvold, made the physical space available and facilitated the procurement of the instrument, including user training.

“The Seahorse instrument will be a useful cell analysis tool in the laboratory instrument portfolio to support researchers in the development of next generation cancer therapies,” commented Nestvold.

The Seahorse is not the type of instrument you would find in just any laboratory.

“There are only around ten instruments of this kind in Norway,” said Erik Brodin from Matriks AS, a company that offers solutions, instruments and support to laboratories across Norway. “Each is worth approximately NOK 2 million.”

Brodin has given training and instructions to a couple of the researchers in the Incubator. These two researchers will pass on their knowledge to the rest of the team.

Oslo Cancer Cluster Incubator are currently in the process of expanding the cell laboratories due to high demand for these kinds of facilities. Meeting rooms are now being converted into laboratories to meet the growing need from tenants.

Designing cells to fight cancer

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How can new designs of T cells improve cell therapy for cancer patients?

Hakan Köksal defended his PhD digitally from Oslo Cancer Cluster Incubator.

Hakan Köksal defended his PhD digitally from Oslo Cancer Cluster Incubator.

This was the question Hakan Köksal attempted to answer in his PhD thesis, which he defended from the Oslo Cancer Cluster Incubator via a digital platform on Thursday 28 May 2020.

Köksal first arrived at Oslo Cancer Cluster Incubator to begin his PhD in October 2016 for the Department of Cellular Therapy, belonging to Oslo University Hospital. Three and a half years later, he is finally finished and has made a discovery that could potentially help cancer patients that are not responding to standard cell therapies.

“Essentially, what we are doing is called adoptive T cell therapy. We try to manufacture designs of chimeric antigen receptors to redirect T cells against cancer cells,” Köksal explained.

Cell therapy is an exciting, new area in cancer research and is a type of immunotherapy. This means that the patient’s immune system is changed in order to recognise and destroy the cancer cells in the body. CAR T cell therapy (CAR is short for chimeric antigen receptor) specifically involves collecting cells from the patient’s blood and changing them in the laboratory.

“We collect T cells, or lymphocytes, from the patients and engineer them so they can detect cancerous cells. Afterwards, they can be reinfused in the patient to destroy the cancer cells.” Hakan Köksal

Novel designs and new approaches

Current CAR T cell therapies have proved successful against several haematological cancers (blood cancers). However, the long-term clinical effects are quite limited and several barriers remain to cure all cancers with cell therapy. One problem Köksal looked at is when lymphoma patients treated with CD19 CAR T therapy relapse with CD19 negative lymphoma.

“We come up with alternative designs and approaches that may have an improved therapeutic effect, a lowered toxicity and improved survival in the body,” Köksal said. “The study we conducted can potentially be used as a standalone therapy or it can be complementary to reduce relapse.”

Standard CAR T therapies use antibody fragments as recognition units to detect cancer cells. In his thesis, Köksal has used a T cell receptor part, which is a different recognition domain, to increase the number of the targetable markers on cancer cells.

“Usually CAR T therapies can only detect proteins on the surface of the cell, but this new design can technically also recognise proteins inside the cell.” Hakan Köksal

Köksal stresses that we cannot know the clinical efficacy of the study before testing it in humans. The furthest they have tested is in mice, which is still a completely different organism from humans.

Read more about the research in this article: “The first Norwegian CAR”

Presenting during corona

Köksal finished his thesis in August 2019 but has not had the opportunity to defend it until now. Due to the ongoing corona situation, he could not present the trial lecture and defence in a filled auditorium but had to make do with an empty room and a laptop.

“It’s completely different. Normally, I would be standing on a stage and looking the audience in the eyes to see if I do well or bad. Now, I couldn’t see the audience, because they couldn’t share their video screens. I could only see my opponents,” Köksal explained.

In March, the corona pandemic affected the researchers in the Incubator too, because there were difficulties getting the necessary deliveries as companies worldwide had limited personnel. The laboratory had to restrict the number of people coming in and meeting rooms were temporarily converted to offices to avoid shared office space. The Incubator never closed completely and stayed open with extra sanitation procedures in place, so that the important research could go on.

Dr. Pierre Dillard and Hakan Köksal are part of the team behind the new study on CD37CAR T-cell therapy for treatment of B-cell lymphoma.

Dr. Pierre Dillard and Hakan Köksal are part of the team behind the new study on CD37CAR T-cell therapy for treatment of B-cell lymphoma.

A collaborative effort

Köksal emphasised that the research behind his PhD thesis has been a team effort. He is thankful to his supervisors at Oslo University Hospital, Else Marit Inderberg, Sebastien Wälchli and June Helene Myklebust, for helping him and giving important guidance during his projects.

It has also meant a lot for him to be a part of the Oslo Cancer Cluster Incubator, Innovation Park and the Oslo Cancer Cluster ecosystem.

“It is good to be in such a translational building. You have one part that has an arm in the clinic and at the same time you have pre-clinical research going on side-by-side with the private companies. You have different niches and you can meet a lot of people with different backgrounds and interests. It gives you new perspectives,” Köksal said.

Köksal thinks the Incubator is a calm, relaxing work environment and not super busy like many other research buildings, where there is a lot of competition going on. In the Incubator, the researchers are united by the common goal to accelerate cancer treatments.

“I feel happy when I see an announcement that a company has reached a new milestone, because it means someone is making an impact and a difference out there.” Hakan Köksal

Köksal will now begin a postdoctoral position and continue his ongoing research projects. He aims to work on the development of cell therapies and hopes to make new breakthroughs on the treatment of solid cancers in the future.

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Björn Klem and Janne Nestvold celebrate that the Oslo Cancer Cluster Incubator has been nominated among Europe's 20 best incubators.

Accelerating cell therapies against cancer

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Oslo Cancer Cluster Incubator has received a grant from the City of Oslo, which will be used to develop the infrastructure for cancer cell therapies.

Oslo Cancer Cluster Incubator has received NOK 300 000 in 2020 from the City of Oslo for a project that will support the development of a type of cancer treatment, known as cell therapies (scroll down to the bottom of this page to read a definition for cell therapy). Different forms of cancer cellular therapies are being explored in the Incubator, including genetically modified immune cells.

Cell therapies have the potential to cure cancer and turn it into a chronic disease. More research is however needed to document the full potential of cell therapies.

Specialised cell laboratory facility

The project involves setting up a specialised facility, which will be used for pre-clinical research and development of cell-based medicinal products.

Oslo Cancer Cluster Incubator’s laboratories are currently used for the design of therapeutic cells and to assess the effectiveness and safety of these cells in pre-clinical testing.

The funding from the City of Oslo will enable Oslo Cancer Cluster Incubator to expand the laboratories with the appropriate infrastructure and equipment. The laboratories will support researchers and companies in their development of new cell-based therapies. The initiative is hopefully a first step to establish production of T cell therapies in Norway as part of building a viable health industry.

Janne Nestvold, laboratory manager at Oslo Cancer Cluster Incubator, will coordinate the project.

“The specialised facility enables the Incubator to contribute in the development of cancer cell-based therapies in a preclinical setting,” said Janne Nestvold.

Several research groups in the Incubator already focus on the development of cell therapies. Now, they will have access to dedicated spaces with much needed equipment.

Supporting public-private research collaboration

Oslo Cancer Cluster Incubator is located next to the Norwegian Radium Hospital, one of Europe’s leading cancer hospitals and a part of Oslo University Hospital.

The Incubator’s partnership with Oslo University Hospital is one-of-a-kind in Norway. Hospital research staff work side-by-side with researchers from private companies and exchange experiences in a collaborative setting. They are also connected, through Oslo Cancer Cluster, to a global network of key players in the cancer research field.

Bjørn Klem, general manager of Oslo Cancer Cluster Incubator, hopes the Incubator can further assist both hospital research staff and researchers from private companies to bring forward new treatments.

“The support from City of Oslo is much appreciated as it enables us to take this important field of cell therapy forward, by supporting commercialisation of the growing number of start-ups in this area. This will allow companies to grow in Norway and create jobs, supporting the vision of the Oslo Science City initiative,” said Bjørn Klem.

About the RIP funding

The regional innovation programme (RIP) for the Oslo region has funded a total of NOK 25 million for business development and innovation in 2020.

The goal of RIP is to strengthen the Oslo region’s international competitiveness in cluster- and network development, entrepreneurship, supplier development and commercialisation.

This year’s award had a special emphasis on the health sector, marked by the ongoing coronavirus pandemic. More than ever, it has become important to support the local innovation clusters and the Norwegian health start-up companies.

 

DEFINITION

CAR T-cell therapy is a type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they more effectively will attack cancer cells. T cells are a specific type of white blood cells taken from a patient’s blood. Then the gene coding for a receptor that binds to a protein on the patient’s cancer cells, is added to the T cell in the laboratory. The receptor is called a chimeric antigen receptor (CAR) and enable the patient immune system to better recognise and fight cancer cells. Large numbers of the CAR T cells are then grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is approved for treatment of some cancer patients (leukaemia or lymfoma) and is studied in the treatment of many other types of cancer with promising effects.
Source: National Cancer Institute

 

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Bjørn Klem, general manager of Oslo Cancer Cluster Incubator, Arild Kristensen, general manager of Smart Care Cluster, and Kathrine Myhre, CEO of Norway Health Tech, look forward to developing the first Norwegian Health Catapult Centre.

Preparing for the first Health Catapult Centre

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Three leading Norwegian health innovation clusters will collaborate on forming a concept for the first Norwegian Health Catapult Centre.

Siva has selected Oslo Cancer Cluster Incubator, Norway Health Tech and Norwegian Smart Care Cluster to proceed to the next round of the Norwegian Catapult call. The three health clusters are now joining forces to apply for a Health Catapult Centre focusing on precision medicine, patient-centric innovation and health services, medical technology and digital health.

The purpose of a Catapult Centre is to support innovative small to medium-sized companies in Norway on their journey to reach the market. A Catapult Centre helps companies to develop prototypes, test, verify, visualise and simulate – so that ideas can be developed faster, better and with less risk.

By inviting the three health clusters to apply together for a Health Catapult Centre, Siva has shown that health innovation and industrialisation is a crucial part of Norwegian industry and trade. This supports the government’s White Paper on the Health Industry , which calls for the building of a strong Norwegian health industry. The current corona pandemic has also highlighted the importance of local health innovation providers and supporting Norwegian early-stage health companies that can quickly deliver solutions to big societal challenges.

The initial application was submitted last December and deemed successful in February. The main topics of precision medicine, patient-centric innovation and health services, medical technology and digital health will now be discussed further over the next six months in the planning of the final Catapult application. The managers of the three clusters look forward to the opportunity of developing a Health Catapult Centre together.

“By joining forces with two strong complementary Norwegian health clusters, we will strengthen the Catapult application by covering a broader range of services to Norwegian health start-ups and scale-ups. A successful application will enable Oslo Cancer Cluster Incubator to support the growth of Norwegian healthcare start-ups together with public healthcare institutions and international industry,” said Bjørn Klem, general manager of Oslo Cancer Cluster Incubator.

“One of the future key factors for the health industry in Norway to scale in the Norwegian and global market, will be to get access to tools, solutions, data and competence to develop, simulate, test, verify and produce their health products and solutions. The aim of the Health Catapult Centre will be to provide the health industry with these services and collaborative partners for the industry to scale. With the Health Catapult Centre up and running, Norway will also be an attractive partner to international health industry, that needs testing and clinical trials for them to launch new health products and solutions on the global market,” said Kathrine Myhre, CEO of Norway Health Tech.

“Together we stand, divided we fall. The three clusters now have an unique opportunity to provide the booming health industry in Norway with tools and services that will speed their development with higher quality, thus enabling world class solutions faster,” said Arild Kristensen, general manager of Norwegian Smart Care Cluster.

The final application for the Health Catapult Centre will be submitted this autumn. If successful, Oslo Cancer Cluster Incubator, Norway Health Tech and Norwegian Smart Care Cluster will jointly become the first Norwegian Health Catapult Centre.

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