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

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

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” 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: 

 

Encouraging news from BerGenBio

A second group of patients have been added to an ongoing phase II clinical study of a drug combination to treat lung cancer.

 

The ongoing trial is a collaborative effort between two members of Oslo Cancer Cluster: Norwegian biopharmaceutical company BerGenBio and US-based pharmaceutical company Merck (known as MSD in Europe). It involves an immune checkpoint inhibitor called bemcentinib, developed by BerGenBio, in combination with an immunotherapy drug called Keytruda (also known as pembrolizumab) from MSD.

 

An immune checkpoint inhibitor is a type of drug that blocks certain proteins made by some types of immune system cells and some cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T cells are able to kill cancer cells better. (Source: cancer.gov)

 

“Throughout 2018, we reported encouraging updates from our ongoing proof-of-concept phase II clinical trial assessing bemcentinib in combination with Keytruda in advanced lung cancer patients post chemotherapy.”
Richard Godfrey, Chief Executive Officer, BerGenBio

 

The second group will involve patients that have been treated with immunotherapy before, but that have experienced a progression of the disease. There are various treatments available for patients with non-small cell lung cancer, but patients often acquire resistance to treatment. New treatments that can overcome these resistance mechanisms are therefore urgently needed.

 

“I am pleased that we are now extending the ongoing trial to test our hypothesis also in patients showing disease progression on checkpoint inhibitors.”
Richard Godfrey, Chief Executive Officer, BerGenBio

 

The aim is to evaluate the anti-tumour activity of this new drug combination. Preliminary results from the second patient group of the study are expected later this year. BerGenBio is in parallel also developing diagnostic tools to see which patients are most likely to benefit from their drug.

 

The decision to extend the trial was based on new positive results from pre-clinical studies, which were presented at the American Association of Cancer Research (AACR) earlier this week. The results open for the possibility to use bemcentinib both as a monotherapy and in combination with other cancer treatments on a broad spectrum of cancers.

 

 

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The panel discussion at our breakfast meeting 27 March 2019. From the left: Jan Frich, Anette Grøvan, Odd Terje Brustugun, Heidi Brorson, Tove Nakken and Markus Moe.

Giving patients a stronger voice

How can the voices of cancer patients be heard when evaluating new methods of treatment?

A breakfast seminar was held yesterday in the series called The Cancer Treatments of the Future. Over 150 people attended at Litteraturhuset in Oslo, among them were relevant key players from the healthcare sector, governmental agencies, patient organisations and the public. The aim was to identify new opportunities to improve patient involvement when evaluating new methods of treatment.

The seminar was jointly arranged by Oslo Cancer Cluster, Legemiddelindustrin (LMI) and The Norwegian Cancer Society. The sponsors of the event were Astra Zeneca, Janssen and MSD.

 

Anne Grethe Erlandsen

Anne Grethe Erlandsen, the State Secretary of the Norwegian Ministry of Health and Care Services.

Anne Grethe Erlandsen, the State Secretary of the Norwegian Ministry of Health and Care Services, first talked about creating a healthcare service with the patient as the starting point. She said that it is important to involve the patient in the decision-making processes to bring in new perspectives, ask questions and challenge the healthcare service.

“The patient is the most radical agent of change in the healthcare sector.”
Anne Grethe Erlandsen

 

Ellen Nilsen

Ellen Nilsen, Special Adviser at Nye Metoder.

Next, Ellen Nilsen, Special Adviser at Nye Metoder, which is the national system for managed introduction of new health technologies within the specialist health service in Norway. Nilsen gave a presentation of Nye Metoder and its processes.

 “Anyone, including patients, their relatives or patient organisations, can submit a proposal for a new method of treatment.” Ellen Nilsen

The proposal is then managed by the regional health authorities in The Commissioning Forum, which commissions a full Health Technology Assessment (HTA) from The Norwegian Medicines Agency. Anyone can submit input to The Commissioning Forum by e-mail or in a form on the website.

Decisions are then made by the regional health authorities in The Decision Forum, based upon the HTA. Patient organisations are also represented in a reference group that meets every six months. The patient representatives are only observers, but have the right to make verbal contributions.

  • Learn more about Nye Metoder by reading this presentation in English from their official website.

 

Health Technology Assessment (HTA) is the evaluation of a new method of treatment, often in comparison to existing treatments. The treatments are assessed according to a set of criteria: the severity of the disease, the utility of the treatment and its cost effectiveness.

 

Anette Grøvan, Senior Adviser at The Norwegian Medicines Agency.

Then, Anette Grøvan, Senior Adviser at The Norwegian Medicines Agency, presented how they are developing a pilot project to involve patients in their HTAs. They have sporadically received input from patients and patient organisations in the past, but they wish to implement a better system for it now.

“Satisfied patients are important to us. Everyone should have a voice, regardless of their diagnosis or disease.” Anette Grøvan

They believe the patients can contribute with their experiences of living with the disease, the quality of existing treatments and their expectations on new treatments.

 

 

A panel discussion, moderated by Markus Moe, the Editor-in-Chief of Dagens Medisin, was then held with the following participants:

  • Tove Nakken, Head of brukerutvalget* at Oslo University Hospital and Deputy Head in Lymfekreftforeningen (The Norwegian Lymphoma Society)
  • Heidi Brorson, member of brukerutvalget* at the South-Eastern Norway Regional Health Authority and Special Adviser in the Norwegian Cancer Society
  • Anette Grøvan, Senior Adviser at The Norwegian Medicines Agency
  • Jan Frich, Chief Medical Officer at the South-Eastern Norway Regional Health Authority and Senior Adviser in the Commissioning Forum
  • Odd Terje Brustugun, oncologist at Drammen Hospital

*”brukerutvalget” is a selected group of patient representatives that exists in each regional health authority

 

The topic of the panel discussion was how to improve patient involvement when evaluating and approving new methods of treatment.

 

Nakken first highlighted the lengthy processes in Norway: “Patients want to take part of the treatments that have been approved in our neighbouring countries. But the bureaucracy in Norway takes too long.”

Brustugun agreed that there is a gap between the treatments available in Norway and abroad, and that this is affecting an ever-growing patient population: “The patient’s perspective is important, because there is a large group of patients that can potentially become long-term survivors if given the new treatments.”

Frich said the overall cost of pharmaceuticals in Norway has actually increased over the years, mostly due to new and expensive cancer therapies. He explained they are legally obliged by Stortinget to evaluate new methods according to a specific set of criteria. The reason that a treatment isn’t approved may be that the effect of it has not been documented well enough.

Brorson called for greater transparency in the decision-making processes: “If there was more openness about the decision-making, the patients would have a greater understanding for it and become better informed.”

Grøvan added: “We are not finished developing the system for patient involvement and there are a lot of considerations to make sure that it becomes structured and fair.”

 

The engaging panel discussion inspired the audience to make their own comments and reflections.

 

Looking forward

The fruitful discussion led to many constructive ideas on how to improve patient involvement. Hopefully, these kinds of collaborative discussions can inform politicians to take the necessary steps forward to improve cancer patients’ lives.

Oslo Cancer Cluster wants to thank the speakers, the sponsors, the organisers and everyone who attended! This discussion will continue at Arendalsuken 2019, at our event August 15. We hope to see you there!

 

  • Here is a summary of the event, written in Norwegian, from LMI’s official website.
Arctic Pharma, a member of Oslo Cancer Cluster, gave students a lecture on the chemistry behind cancer treatments.

Chemistry with mutual benefits

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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Transporting patients

Student Jørgen Amdim got to experience life as an orderly on his one-week placement at the Norwegian Radium Hospital.

 

Transporting patients in Norway’s biggest cancer hospital is strenuous both physically and psychologically. “But it’s really good,” said Jørgen Amdim, who is studying the program Healthcare, childhood and youth development at Ullern Upper Secondary School. His one-week placement was at the Transport Section at the Norwegian Radium Hospital. The work experience certainly gave him a taste for more.

Jørgen has previously worked in a nursing home, but he found the work a little tedious. He enjoyed being an orderly though and asked the school if there were any available placements.

An orderly is an attendant in a hospital who is responsible for, among other things, transporting patients, medical equipment and other essential materials. Jørgen spent one week as an orderly at the Radium Hospital and he loved it. He enjoyed it so much that he wants to work there again during the summer of 2019.

Knut Arve Kristiansen, the Head of the Transport Section, has worked at the Radium Hospital for 30 years and praised Jørgen:

“He was a perfect addition to our team, and we are very happy with him.”

 

 

80 km per week

Jørgen enjoys manual labour, which is great if you want to become an orderly. Wheeling around heavy medical equipment or patients in beds and wheel chairs is hard work. Knut Arve explained:

”As orderlies, we’re constantly on the go, and we could end up walking around 80 kilometres on hard floors during a week of work.

“It can be strenuous for the body, so we have to regularly do strength exercises to keep fit,” Knut Arve continued.

Knut Arve only had positive things to say about Jørgen and he hopes that Jørgen will want to return to the Transport Section for a summer job as an orderly.

“Jørgen is a social person and very well liked. This is important for patients when they are transported between examinations and the rooms they are staying in,” said Knut Arve.

Jørgen praises the work environment and especially the warm welcome he received from the other staff.

Jørgen has constantly been accompanied by a colleague from the section during his stay, because he is not allowed to do much on his own when on a placement. If he returns for a summer job, things will be different. Then he will have to work more independently and take responsibility if an emergency should occur while he is transporting a patient.

The orderlies are also responsible for transporting food and medication. To newcomers, the Radium Hospital can appear to be a huge labyrinth, especially outside the wards. The hospital is also currently being renovated, because a new hospital is being built. A sense of direction is therefore essential for anyone finding their way through the building.

 

A future in health

Jørgen does not necessarily want to become an orderly, but sees himself working in healthcare:

“I would really like to work in an emergency room – receiving ill and injured people at the hospital when they arrive in an ambulance. But I think working as an orderly is very exciting too, so I don’t want to exclude it as an option.”

Knut Arve says that a trade certificate is required to work as an orderly and that they currently offer placements for several apprentices in the section. Students need to study Healthcare, childhood and youth development during upper secondary school and then finish a two-year apprenticeship to obtain their trade certificate as an orderly.

”Workdays here are very varied and you meet many different people. It is really fun to talk to people and no two days are the same. I have really enjoyed it.” said Jørgen.

 

Attracting and developing the life science talents of the future is an essential goal for Oslo Cancer Cluster. One way to do that is to take students outside the traditional classroom setting and invite them to work placements and educational lectures. These collaborations between industry and academia give the students a unique insight into the specialist skills needed to become tomorrow’s researchers and entrepreneurs.

  • Find out more about Oslo Cancer Cluster’s school collaboration with Ullern Upper Secondary School.

 

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Dr. Nadia Mensali (in the middle) and her colleagues from Oslo University Hospital in their cell lab at Oslo Cancer Cluster Incubator. Photo: Christopher Olssøn

Natural killer cells dressed to kill cancer cells

New research: A new study may potentially enable scientists to provide cancer immunotherapy that is cheaper, faster and more manageable.

New work by researchers with laboratories at Oslo Cancer Cluster Incubator may help to dramatically improve a T cell-based immunotherapy approach so that it can benefit many more patients.

 

T cell assassins

T cells are the professional killers of the immune system – they have a unique capability to specifically recognize ‘foreign’ material, such as infected cells or cancer cells. This highly specific recognition is achieved through receptors on the surface of T cells, named T cell receptors (TCRs). Once its receptor recognizes foreign material, a T cell becomes activated and triggers the killing of the infected or cancerous cell.

T cell receptors (TCRs): receptors on the surface of T cells, that recognize foreign material and activate the T cell. This triggers the killing of the infected or cancerous cell by the T cell.

 

Adoptive cell therapy 

Unfortunately, many cancers have adapted fiendish ways to avoid recognition and killing by T cells. To combat this issue, an immunotherapy approach known as adoptive cell therapy (ACT) has been developed in recent years. One such ACT approach is based on the injection of modified (or ‘re-directed’) T cells into patients. The approach is further explained in the illustration below.

 

Illustration from the research paper ‘NK cells specifically TCR-dressed to kill cancer cells’.

 

The left side of the illustration shows how redirected T-cell therapy involves:

1) Harvesting T cells from a cancer patient

2) Genetic manipulation of T cells to make them express an ideal receptor for recognizing the patient’s cancer cells

3) Growing T cells in culture to produce high cell numbers

4) Treating patients with large quantities of redirected T cells, which will now recognize and kill cancer cells more effectively

 

An alternative approach 

Adoptive T cell therapy has delivered very encouraging results for some cancer patients, but its application on a larger scale has been limited by the time consuming and costly nature of this approach. In addition, the quality of T cells isolated from patients who have already been through multiple rounds of therapy can sometimes be poor.

Researchers have long searched for a more automated form of adoptive cell therapy that would facilitate faster and more cost-effective T cell-based cancer immunotherapy.

One approach that has seen some success involves the use of different immune cells called Natural Killer cells – NK cells in brief.

Despite their great potential, NK cells have unfortunately not yet been proven to provide a successful alternative to standard T cell-based cancer immunotherapy. One major reason for this may be that, because NK cells do not possess T cell receptors, they are not very effective at specifically detecting and killing cancer cells.

NK cell lines: Natural Killer cells (NK cells) have the ability to recognise and kill infected or cancerous cells. Scientists have been able to manipulate human NK cells so that they grow without restriction in the lab. This is called a cell line. It enables a continuous and unlimited source of NK cells that could be used to treat cancer patients.

 

Cells dressed to kill

The group led by Dr. Sébastien Wälchli and Dr. Else Marit Inderberg at the Department of Cellular Therapy aimed to address this issue and improve NK cell-based therapies.

They reasoned that by editing NK cells to display anti-cancer TCRs on their cell surface they could combine the practical benefits of NK cells with the potent cancer killing capabilities of T cells. This is shown in the right hand side of the illustration above.

The researchers found that by simply switching on the production of a protein complex called CD3, which associates with the TCR and is required for T cell activation, they could indeed induce NK cells to display active TCRs. These ‘TCR-NK cells’ acted just like normal T cells, including their ability to form functional connections to cancer cells and subsequently mount an appropriate T cell-like response to kill cancer cells.

This was a surprising and important finding, as it was not previously known that NK cells could accommodate TCR signaling.

This video shows TCR-NK cell-mediated killing of cancer cells in culture. The tumour cells are marked in green. Tumour cells that start dying become blue. The overlapping colours show dead tumour cells.

 

The researchers went on to show that TCR-NK cells not only targeted isolated cancer cells, but also whole tumours.

The method was proven to be effective in preclinical studies of human colorectal cancer cells in the lab and in an animal model.  This demonstrates its potential as an effective new form of cancer immunotherapy.

 

Paving the way

Lead researcher Dr. Nadia Mensali said:

“These findings pave the way to the development of a less expensive, ready-to-use universal TCR-based cell therapy. By producing an expansive ‘biobank’ of TCR-NK cells that detect common mutations found in human cancers, doctors could select suitable TCR-NK cells for each patient and apply them rapidly to treatment regimens”.

Whilst further studies are needed to confirm the suitability of TCR-NK cells for widespread treatment of cancer patients, the researchers hope that these findings will be the first step on the road towards off-the-shelf immunotherapy drugs.

 

  • Read the whole research paper at Science Direct. The paper is called “NK cells specifically TCR-dressed to kill cancer cells”.
  • The researchers behind the publication consists of Nadia Mensali, Pierre Dillard, Michael Hebeisen, Susanne Lorenz, Theodossis Theodossiou, Marit Renée Myhre, Anne Fåne, Gustav Gaudernack, Gunnar Kvalheim, June Helen Myklebust, Else Marit Inderberg, Sébastien Wälchli.
  • Read more about research from this research group in this article from January.
  • Read more about Natural Killer cells in this Wikipedia article.

 

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

The Incubator Labs are expanding

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

 

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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Dr. Jon Amund Kyte is the new Head at the Department of Experimental Cancer Treatment at OUH.

Attracting clinical trials to Norway

Dr. Jon Amund Kyte at Oslo University Hospital (OUH) and Oslo Cancer Cluster share the common goal of bringing more clinical trials to Norway.

 

Jon Amund Kyte is the new Head at the Department of Experimental Cancer Treatment at OUH. He also runs three separate clinical trials and is the leader of a research group at the Department of Cancer Immunology, where he develops novel CAR T cell therapy and conducts translational studies.

Kyte aims to increase the number of and improve the quality of clinical trials in Norway. He says this will contribute to more patients gaining access to novel cancer treatments and to improving the efficacy of cancer therapies.

“The only way to improve cancer treatment is to have clinical trials,” said Kyte.

Oslo Cancer Cluster also wants to bring more clinical trials to Norway to develop innovative cancer medicines. The ambition is to enable faster patient recruitment from across the Nordic region, so that many more can benefit from new treatments, such as immunotherapy.

 

CAR T cells are produced by isolating specific cells of the immune system (T cells) from a cancer patient and modifying them so that they become more effective at recognizing and killing cancer cells.

 

Promising advances

Immunotherapy represents a new type of cancer treatment, which activates the patient’s immune-system to fight off the cancer cells. It gives doctors the opportunity to help patients that previously had limited treatment options. Most types of immunotherapy also cause less side effects than traditional cancer treatments.

“The important point is that immunotherapy can have a long-term effect,” said Kyte.

“Most patients that experience a recurrence or progression of the disease cannot be cured. The traditional treatments only have a limited, short-term effect on them. But immunotherapy may have a long-term effect on the patient – and, in some cases, even cure the disease.”

 

Two big challenges

Immunotherapy may sound like a miracle drug, but researchers still have a long way to go to perfect the treatment for all cancer patients. Kyte highlights two of the biggest barriers that remain.

“One challenge is to develop immunotherapy so that it works efficiently on all types of cancer. The other challenge is to learn how to choose personalised treatment plans: to identify an individual’s biomarkers and find out which treatment will be effective for that specific patient.”

A biomarker is a biological molecule in the patient’s body and these may be used to see how well a patient will respond to a certain treatment. Kyte said that to develop immunotherapy, there needs to be more clinical trials. It is the only way for researchers to find out how to activate an immune response in the patient’s body.

“A big potential for development lies in trying different possible combinations of cancer treatments. In my clinical trials, for example, we combine immunotherapy with immunogenic chemotherapy or radiation therapy,” Kyte explained.

 

Jon Amund Kyte presenting the Clinical Trial Unit.

The Clinical Trial Unit are experts in assisting companies and researchers to conduct clinical trials in Norway.

 

Welcome, companies

OUH has a long history of conducting clinical trials and is an appealing option for both researchers, doctors and companies that wish to initiate their own trials. Kyte welcomes more companies to conduct clinical trials at OUH:

“The more clinical trials that are conducted here by companies, the stronger our clinical research environment becomes and our ability to run our own studies is also strengthened.”

The Clinical Trial Unit in Kyte’s department offers its services to companies that want to run a clinical trial at OUH. They have extensive background knowledge of how the hospital is organised and which approvals are needed to conduct a clinical trial in Norway. They can step in as project coordinator for companies that need help to get their clinical trials up and running.

“We are highly experienced in applying for approvals in Norway. When you run a clinical trial, there are regulations from the Norwegian Medicines Agency and the ethical committee and other governmental agencies. A clinical trial also involves many different parts of the hospital – the departments of pathology and radiology, the laboratories, the infusion unit, the hospital wards and out-patient clinic and the administrative offices that oversee different agreements, data management and biobanking.”

 

Nordic clinical trials

All these administrative obstacles may appear discouraging, but there are many convincing reasons to conduct a clinical trial in Norway.

“The Oslo University Hospital is a good place to run a clinical trial, because in terms of the number of cancer patients, it is one of the largest hospitals in Europe. Norwegian healthcare is also extremely well-organised. Patients are rarely lost to follow-up, because there are no private healthcare alternatives and patients rarely move out of the country,” Kyte explained.

The Clinical Trial Unit is also taking part in the development Nordic Nect, a collaboration to recruit patients from the entire Nordic region to clinical trials. The plan is to have one hospital where the clinical study is conducted and to involve patients from Sweden, Denmark, Finland and Norway. There will then be a population of 25 million people from which to recruit patients, which opens the possibility for larger clinical trials.

“This is a good thing for the companies that want to run clinical trials in Norway. It is also good for the researchers. But most of all, it is good for the patients – who have the opportunity to take part in more novel cancer treatments,” said Kyte.

 

 

 

 

Promising start for expansion group of Targovax clinical trial

Doctor examining the birthmark of a female patient

Targovax, one of the members of Oslo Cancer Cluster, has begun an expansion patient group in the clinical trial of a drug to treat skin cancer.

The company Targovax is developing immune activators to target solid tumours that are difficult to treat. The drug in question, called ONCOS-102, is aimed at patients with malignant melanoma (skin cancer) who have either been through chemotherapy, biological therapy or surgery and experienced a recurrence or progression of the cancer.

 

How does it work?

The immune activators work by activating the patient’s own immune system to attack the cancer cells. The drug that is now being tested is a genetically modified oncolytic adenovirus, a type of virus that has been designed to infect in the cancer cells and then replicate.

 

Initial positive results

Targovax, a member of the Oslo Cancer Cluster, are developing a treatment for skin cancer.

In September 2018, the first six patients had been treated with 3 injections of the drug and all of them showed a strong activation of their immune systems – one patient even had a complete response. The results suggested that the patients could benefit from more injections of the drug.

“The results seen to date with only three injections of ONCOS-102 are promising, and we are confident that by increasing to twelve injections we will release the full potential of ONCOS-102 to reactivate these patients to respond to Keytruda treatment,” said Magnus Jäderberg, CMO of Targovax.

 

Expansion patient group

On 11 February 2019, the first patient in the expansion group of the phase I trial was injected with ONCOS-102. The patient will be treated in combination with pembrolizumab, also known as Keytruda, an immunotherapy drug that works as an immune checkpoint inhibitor. This means that the drug involves antibodies, which “unlock” the protective mechanisms of the cancer cells so the immune system then can destroy them.

 

For more information, read the full press release from Targovax.

A new drug combination from Vaccibody and Roche may help to treat patients with cervical cancer.

New collaboration aims to treat cervical cancer

Hands cradling female reproductive system

The companies Vaccibody and Roche have started a new collaboration to investigate a drug combination to treat patients with advanced cervical cancer.

 

Both companies are members of Oslo Cancer Cluster and are involved in the development of novel cancer treatments.

Martin Bonde, CEO of Vaccibody, said: “We are very pleased with this collaboration. This is an important study as it explores a novel targeted treatment approach that addresses the high medical need of patients with advanced cervical cancer.”

 

Cervical cancer is the most commonly occurring cancer among women in developing countries and is the second most commonly occurring cancer amongst women worldwide.

 

Vaccibody is a vaccine company that aims to develop and discover new immunotherapies to treat difficult forms of cancer. They have developed a therapeutic DNA vaccine that treats cancers caused by HPV (the human papillomavirus).

 

Cervical cancer is caused by high risk HPV. HPV16 is the type that most frequently causes cancer.

 

Immunotherapy is a type of cancer treatment that aims to switch on a patient’s immune system to kill cancer cells.

 

Roche is a healthcare company that has developed an immune-checkpoint inhibitor. Now Vaccibody wants to test their vaccine in combination with the immune-checkpoint inhibitor designed by Roche.

 

An immune checkpoint inhibitor is a type of drug that blocks certain proteins made by some types of cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T cells are able to kill cancer cells better.

 

Agnete Fredriksen, President and CSO of Vaccibody, said that the combination of the two drugs build on the positive results seen when their vaccine has been used on patients with cervical cancer. Therefore they now expect to see positive results when they combine the vaccine with an immune checkpoint inhibitor.

 

During the second half of 2019, Vaccibody expects to begin the phase II study, which will involve 50 patients. It will assess the safety of the drug, its ability to invoke a response in the immune system, how the patients tolerate it and how efficient the drug is. The group for this new drug combination involves patients with advanced cervical cancer.

 

Raised NOK 230 million

Vaccibody also raised NOK 230 million (EUR 23.6 Million) in a private placement the same week. The sum was indeed placed all within one day, according to Agnete Fredriksen.

The proceeds from the share sales will be used to conduct the phase II clinical study of the drug combination from Vaccibody and Roche. The money will also go to the preparation of expansion patient groups in Vaccibody’s clinical trials and to generate corporate purposes.

 

For more information, read the press release from Vaccibody.