Anette Weyergang demonstrated the PCI technology to the Norwegian Prime Minister Erna Solberg during her visit to Oslo Cancer Cluster Innovation Park.

Radforsk to invest NOK 4.5 million in cancer research

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Radforsk, the Radium Hospital Research Foundation, a partner of Oslo Cancer Cluster, is awarding several million Norwegian kroner to new research that fights cancer with light.

Radforsk is an evergreen investor focusing on companies that develop cancer treatment. Since its inception in 1986, Radforsk has allocated NOK 200 million of its profit back into cancer research at Oslo University Hospital. This year, four researchers will be awarded a total of NOK 4.5 million. One of them is Anette Weyergang, who will receive NOK 3.75 million over a three-year period.

“I’m so happy for this grant. As researchers, we have to find funding for our own projects. I didn’t have any funding for the project I have now applied and been granted funds for,” says Anette Weyergang.

Anette Weyergang is one of the researchers who has received funding from Radforsk.

Anette Weyergang is a project group manager and senior researcher in a research group led by Kristian Berg. The group conducts research in the field of photodynamic therapy (PDT) and photochemical internalisation (PCI). Radforsk’s portfolio company and Oslo Cancer Cluster member PCI Biotech is based on this group’s research.

What is PDT / PCI? Cancer research in the field of photodynamic therapy and photochemical internalisation studies the use of light in direct cancer treatment in combination with drugs, or to deliver drugs that can treat cancer cells or organs affected by cancer.

 

Weyergang is the first researcher ever to receive several million kroner over the course of several years from Radforsk.

“We have donated a total of NOK 200 million to cancer research at Oslo University Hospital, of which NOK 25 million have gone to research in PDT/PCI. We have previously awarded smaller amounts to several researchers, but we now want to use some of our funds to focus on projects we believe in,” says Jónas Einarsson, CEO of Radforsk.

By the deadline on 15 February 2019, Radforsk received a total of eight applications, which were then assessed by external experts.

 

The new research focuses on how to use light to release the cancer drugs more efficiently inside the cancer cells.

 

New use of PCI technology

PCI is a technology for delivering drugs and other molecules into the cancer cells and then releasing them by means of light. This allows for a targeted cancer treatment with fewer side effects for patients.

Weyergang will use the funds from Radforsk to research whether PCI technology can be used to make targeted cancer treatment even more precise.

“The project aims to find a method for delivering antibodies to cancer cells using PCI technology. This has never been done before, and if we succeed, it can open up brand new possibilities for using this technology,” says Weyergang.

Initially, she will focus on glioblastoma, which is the most serious form of brain cancer. Glioblastoma is resistant to both chemotherapy and radiotherapy, and has a very high mortality rate.

“This is translational research, so human trials are still a long way off. We will now use both glioblastoma cell lines and animal experimentation to test our hypothesis. We do this to establish what is called a “proof of concept”, which we need to move on to clinical testing,” says Weyergang.

 

The other researchers who have received funding for PDT/PCI research from Radforsk in 2019 are:

  • Kristian Berg and Henry Hirschberg Beckman: NOK 207,500
  • Qian Peng: NOK 300,000
  • Mpuldy Sioud: NOK 300,000

 

What is Radforsk?

  • Since its formation in 1986, Radforsk has generated NOK 600 million in fund assets and channelled NOK 200 million to cancer research, based on a loan of NOK 1 million in equity back in 1986.
  • During this period, NOK 200 million have found its way back to the researchers whose ideas Radforsk has helped to commercialise.
  • NOK 25 million have gone to research in photodynamic therapy (PDT) and photochemical internalisation (PCI). In total, NOK 40 million will be awarded to this research.

 

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From the left: Hakan Köksal, PhD student, and Pierre Dillard, scientist, are splitting cells in the lab at Oslo Cancer Cluster Incubator. They are two of the scientists behind the new Norwegian study described in this article.

The first Norwegian CAR

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Made in Oslo by a team of researchers from Oslo University Hospital, the first ever Norwegian CAR T cell is now a fact. A potential treatment based on this result depends on a clinical study.

A new Norwegian study shows a genetically modified cell-line with great potential as treatment for patients that are not responding to established CAR T cell therapies. This form of immuno-therapy for cancer patients has recently been approved in many countries, including Norway.

“We hope that the Norwegian authorities will be interested in transforming this research into benefits for Norwegian patients.” Hakan Köksal

 

 

What is a CAR?

Before we go into the research, let us clarify an essential question. What is a CAR? Chimeric antigen receptor (CAR) T cells are T cells that have been genetically engineered to produce an artificialreceptorwhich binds a protein on cancer cells.

How does this work? T cells naturally recognize threats to the body using their T cell receptors, but cancer cells can lock onto those receptors and deactivate them. The new CAR T cell therapies are in fact genetic manipulations used to lure a T cell to make it kill cancer cells. This is what a CAR is doing, indeed CARs replace the natural T-cell receptors in any T cells and give them the power to recognize the defined target – the cancer cell.

CAR-T cell therapy is used as cancer therapy for patients with B-cell malignancies that do not respond to other treatments.

 A severe consequence of using CAR T cell therapy is that it effectively wipes out all the B cells in the patient’s body — not only the cancerous leukemia cells or the lymphoma, but the healthy B cells as well. Since B-cells are an important part of the immune system, it goes without saying that the treatment comes with risks.

Micrograph of actin cytoskeleton of T-cells. The cell is about 10µm in diameter. Photo: Pierre Dillard

Micrograph of actin cytoskeleton of T-cells. The cell is about 10µm in diameter. Photo: Pierre Dillard

T cells: T lymphocytes (T cells) have the capacity to kill cancer cells. These T cells are a subtype of white blood cells and play a central role in cell-mediated immunity.

 

Made in Norway  

Now let us move on to the new research. This particular construct was designed from an antibody that was isolated in the 1980’s at the Radium Hospital in Oslo.

The CAR construct was designed, manufactured and validated in two laboratories in the Radium Hospital campus. One is the laboratory of Immunomonitoring and Translational Research of the Department of Cellular Therapy, OUH, located at the Oslo Cancer Cluster Incubator. This laboratory is led by Else Marit Inderberg and Sébastien Wälchli. The other is the laboratory of the Lymphoma biology group of the Department of Cancer Immunology, Institute for Cancer Research, OUH. This laboratory is led by June Helen Myklebust and Erlend B. Smeland.

“Even the mouse was Norwegian.” Hakan Köksal

The pre-clinical work that made the Norwegian CAR was completed in March 2019.

In the research paper “Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma”, published in the journal Blood Advances, the research team tests an artificially produced construct calledCD37CAR and finds that it is especially promising for patients suffering from multiple types of B-cell lymphoma. This may be treated successfully with novel cell-based therapy.

It now needs to be approved by the authorities and gain financial support to be further tested in a clinical study in order to benefit Norwegian patients.

 

The first CAR-therapy

CAR-based therapy gained full attention when the common B-cell marker CD19 was targeted and made the basis for the CAR T cell therapy known as Kymriah (tisagenlecleucel) from Novartis.

It quickly became known as the first gene therapy allowed in the US when it was approved by the US Food and Drug Administration (FDA) just last year, in 2018, to treat certain children and young adults with B-cell acute lymphoblastic leukemia. Shortly after, the European Commission also approved this CAR T cell therapy for young European patients. The Norwegian Medicines Agency soon followed and approved the treatment in Norway.

“CD19CAR was the first CAR construct ever developed, but nowadays more and more limitations to this treatment have emerged. The development of new CAR strategies targeting different antigens has become a growing need.” Dr. Pierre Dillard

 

Not effective for all

Although the CD19CAR T cell therapy has shown impressive clinical responses in B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, not all patients respond to this CAR T treatment.

In fact, patients can become resistant to CD19CAR. Such relapse has been observed in roughly 30% of the studies of this treatment. Thus, alternative B-cell targets need to be discovered and evaluated. CD37 is one of them.

“You could target any antigen to get a new CAR, but it is always a matter of safety and specificity.” Hakan Köksal said.

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.

 

The Norwegian plan B

The novel Norwegian CAR T is the perfect option B to the CD19CAR.

 “The more ammunition we have against the tumours, the more likely we are to get better response rates in the patients.” Hakan Köksal

The CD37CAR T cells tested in mouse models in this Norwegian study, show great potential as treatment for patients that are not responding to the established CD19CAR-treatment.

“More and more labs are studying the possibility of using CAR therapy as combination, i.e. CAR treatments targeting different antigens. Such a strategy will significantly lower the probability of patients relapsing.” Dr. Pierre Dillard said.

The CD37CAR still needs to be tested clinically. The scientists at OUS underline the importance of keeping the developed CD37CAR in Norway and having it tested in a clinical trial.

“It is a point to keep it here and potentially save patients here. We would like to see the first CD37CAR clinical study here in Norway.” Hakan Köksal

 

More from the Translational Research Lab of the Department of Cellular Therapy, OUH: 

 

Arctic Pharma, a member of Oslo Cancer Cluster, gave students a lecture on the chemistry behind cancer treatments.

Chemistry with mutual benefits

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Students were taught about the chemistry behind developing cancer treatments in the Oslo Cancer Cluster Incubator.

In February, forty chemistry students were given a memorable specialisation day on the subject of the chemistry behind developing cancer treatments. The company Arctic Pharma in Oslo Cancer Cluster Incubator invited them to the lab and gave a long and detailed lecture on the chemistry behind the medication they are developing to treat cancer.

Karl J. Bonney, who is a researcher in the company, started the day with an interactive lecture in English about the chemistry of the substance Arctic Pharma hopes will be effective against cancer.

Bonney emphasised to the students that the company is in the early stages of the development, and that it will take approximately three to four years before they are potentially able to start clinical trials on humans to see whether the substance is effective.

The pupils who are studying chemistry as their specialisation in the last year of upper secondary school were obviously fascinated by what they heard. They asked many important questions both to the lecturer, Bonney, and the chemistry teacher, Karsten, who participated to explain the most difficult terms in Norwegian.

 

Sugar-hungry cancer cells

Arctic Pharma is exploiting a well-known biological fact regarding cancer cells, namely that they like sugar, which means they have a sweet tooth. This is called the Warburg effect, and, so far, nobody has used it in the treatment of cancer. Since this is such a characteristic aspect of cancer cells, it would make sense to think that this could be a viable starting point for treatment.

Arctic Pharma is one of the smaller companies in Oslo Cancer Cluster Incubator and is co-located with Ullern Upper Secondary School. Bonney has been permitted to use the school’s chemistry lab to test the chemical substance being developed to attack the Warburg effect.

The chemistry day at the company was organised to return the favour and to inspire the young chemistry students to keep studying chemistry at a university or university college.

 

 

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Three offices have been converted into extra laboratory space for the members of the Incubator.

The Incubator Labs are expanding

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One of the tenants in the Oslo Cancer Cluster Incubator.

The laboratories at Oslo Cancer Cluster Incubator are expanding to meet increasing demand from members.

 

Oslo Cancer Cluster Incubator has recently converted three offices into new laboratories to accommodate the rising demand from their members.

From the opening in 2015, the laboratories in the Incubator have been a great success. Several of the start-ups have expanded their work force and require more offices and lab space.

The new laboratory is jointly occupied by Zelluna Immunotherapy and the Department of Cellular Therapy (Oslo University Hospital). The Institute for Energy Technology and Arctic Pharma have also expanded their laboratories with an extra room each.

The laboratories are now running at full capacity, but there is some space available in the shared labs. Some of the members of the Incubator offer their services to outside companies who are in need of getting lab work done.

“Our ambition is to grow the Incubator Labs further into the new Innovation Park next door.” Bjørn Klem, General Manager

 

Office plan of the OCC Incubator

The Incubator occupies over 550 square meters. Offices have been converted into labs to meet the growing interest from the members.

 

A unique model

The Incubator Labs follow a unique model, which offers both private laboratories and fully equipped shared laboratories. The private laboratories are leased with furniture, water supply, electricity and ventilation. The companies bring their own equipment depending on their needs.

Shared laboratories, including a bacteria lab, a cell lab and wet lab, are leased including basic equipment with the opportunity for companies to bring their own if shared by all tenants. All laboratories share the common support facilities including a cold room for storage, a laundry room, and storage room including cell tanks and nitrogen gas.

“This model of a shared laboratory is very unusual,” said Janne Nestvold, Laboratory Manager at the Oslo Cancer Cluster Incubator.

The advantage of working in a shared lab is that companies can avoid the costs and limitations associated with setting up and managing a laboratory. A broad range of general equipment, including more advanced, analytical instruments, are provided by the Incubator.

”It would be too expensive for a small company to buy all this equipment themselves.” Janne Nestvold, Laboratory Manager

 

The Department of Cellular Therapy (Oslo University Hospital) are one of the members using the shared lab. Photograph by Christopher Olssøn

 

 

Open atmosphere

The laboratories have an open and light atmosphere. Large windows provide ample lighting and all spaces are kept clean and tidy. The halls are neatly lined with closets and plastic containers for extra storage.

The general mood is calm and friendly. Nestvold communicates daily with the users about changes, updates and improvements, which sets an informal tone. Thanks to monthly lab meetings, the users are also involved in the decision-making process. The companies often work side-by-side or in teams, fostering collaboration rather than competition. There is therefore a strong workplace culture based upon flexibility and mutual respect.

The companies often work side-by-side or in teams, fostering collaboration rather than competition.

Nestvold also ensures that the high demands on the infrastructure of the laboratory are met. She has put agreements in place to facilitate the members’ needs, such as the washing of lab coats, pipette service and shipping packages on dry ice. With all these services included, the Incubator Labs are attractive for researchers and companies to carry out their cancer research.

 

Over the years, Nordic Nanovector, OncoInvent, Targovax, Intersint, OncoImmunity have conducted research in the laboratories. Now, Arctic Pharma, the Department of Cellular Therapy (Oslo University Hospital), GE Healthcare, the Institute for Energy Technology, Lytix BioPharma, NorGenotech, Ultimovacs and Zelluna Immunotherapy are using the Incubator Labs to develop their cancer treatments.

 

  • For more information about the Incubator Lab, get in touch with Janne Nestvold.

 

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