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.

 

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

Oslo, Norway, 26.04.2017. Photographs from Oslo Cancer Cluster (OCC), an oncology research and industry cluster dedicated to improving the lives of cancer patients by accelerating the development of new cancer diagnostics and medicines. Photographs by Christopher Olssøn

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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