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The Ullern students visited the Core Facility for Advanced Light Microscopy at Oslo University Hospital.

Advanced microscopy on the timetable

This article was first published in Norwegian on our School Collaboration website.

How can we learn more about cancer cells by using advanced microscopes?

A microscope is an important tool for scientists in many different branches of research. In February, four first-year students from the Researcher programme at Ullern Upper Secondary School got to test multiple different microscopes at the Core Facility for Advanced Light Microscopy, The Gaustad node, at Rikshospitalet (Oslo University Hospital).

Isha Mohal, Peder Nerland Hellesylt, Christofer Naranjo Woxholt and Henrik Eidsaae Corneliussen are sitting in a small, rectangular room, which belongs to the research group Experimental Cancer Therapy at Oslo University Hospital.

“If you sit next to me, you can see better what I am doing,” says Emma Lång to the students.

Emma Lång is a researcher at the research group Experimental Cancer Therapy. She explains to Henrik and Isha how the advanced microscope, connected to the computer behind her, can record videos of living cells. Photo: Elisabeth Kirkeng Andersen

Emma Lång is a researcher in the research group Experimental Cancer Therapy. She explains to Henrik and Isha how the advanced microscope, connected to the computer behind her, can record videos of living cells. Photo: Elisabeth Kirkeng Andersen

It is the second day of the work placement for the Ullern students. Lång will show them how she is setting up a very special microscope with the somewhat cryptical name “ImageXpress Micro”.

The microscope is so special that it is the only one in the entire Oslo region and Eastern Norway. The unique thing about the microscope is that it creates videos of thousands of living cells over a long time period. This enables the researchers to understand more about how the cells move.

This is important knowledge in the research on cancer and wound healing, which this research group is working on.

The students sit down beside Lång and follow what she is doing closely. The microscope is entirely automatic, so all the settings are done on a computer. Later the same day, the students will use the microscope themselves to record videos of cells that they have been working on from the day before.

Learning from practical work

This is the first work placement for the students from the Research programme – and they are really enjoying it.

“It is fun to see what the researchers are doing and to try it out ourselves in practice,” says Peder.

“We have done some work with pipettes and worked in the laboratory at school, so we are already familiar with some of the practical handiwork. It is fun to try it out in a real research setting,” says Isha.

She likes that the placement gives some insight into what a career in research and cellular biology can be like.

“I am more interested to work in cellular biology after this placement, but I haven’t decided anything yet. I think we are learning things in an exciting way. It is practical learning and not as theoretical as it is usually in school,” says Peder.

“I absolutely see this as an opportunity to become a researcher. It is great to have so much science subjects as we have on the Researcher programme,” says Henrik and Isha agrees.

“I am very interested in the natural sciences. We have a lot of theory in school and it is fun to come out into the hospital and into companies to see how researchers work – and to try it out ourselves,” says Isha.

Christofer also thinks it is interesting, but he is more interested in data and other general subjects.

“That’s great, Christofer,” Lång says. “Research needs more people with good data knowledge. Do you see the computer over there? It costs NOK 100 000 and it will be used to develop machine learning and a technique called ‘deep learning’ on the data produced from our microscopes. Maybe in a few years time, computers will be analysing the microscope images and videos that we are recording now.”

Images of cells

Yesterday, Isha, Peder, Christofer and Henrik worked on cells in the laboratory. They learned a technique to fixate cells. Then, they coloured the cells with antibodies that turn blue when they bind to the core of the cell and with a protein called actin that turns green. Actin performs several functions in the cell, it is both inside the cell structure and functions as threads of communication between the cells.

Stig Ove Bøe leads the research group was visited by the four students from the Research programme at Ullern Upper Secondary School for two days. Here, he is preparing the images of skin cells that the students worked on the day before. Photo: Elisabeth Kirkeng Andersen

Stig Ove Bøe leads the research group that was visited by the four students from the Research programme at Ullern Upper Secondary School for two days. Here, he is preparing the images of skin cells that the students worked on the day before. Photo: Elisabeth Kirkeng Andersen

Now, the students are looking at the results uploaded to a computer in an advanced image editing software program that can visualise the cells as two- or three-dimensional.

“These are the skin cells you coloured yesterday. Can you see that the cells make up one close network? The reason for this is that it is skin and it is supposed to be impenetrable. Can you also see that the single cells act differently at the edge than closer inside? It is our job to explain why and how,” Bøe explains to the students.

The students look and nod with interest.

After the placement, researchers at Rikshospitalet (Oslo University Hospital) have worked more on the images and videos that the students created.

These have been delivered to the students and will be used when they make a presentation of the placement and everything they learned to the rest of the students at the Research programme.

You can see the cell image below.

A three-dimensional image of the skin cells that the students have coloured. Photo: Emma Lång

A three-dimensional image of the skin cells that the students have coloured. Photo: Emma Lång

What is cell migration?

The research group “Experimental Cancer Therapy” led by Dr Stig Ove Bøe at Rikshospitalet are researching how cells move, which is called cell migration in scientific terms.

Cell migration plays a central role in many of the body’s physiological functions, such as the immune system and wound healing. Cell migration is also essential for cancer, since cancer cells can spread from the location of the tumour to other organs of the body.

Cells use different mechanisms to migrate. They can move as single cells or they can move collectively. Thousands of cells can, for example, cooperate so they can move in the same direction.

The research group uses many different microscopy-based methods to research cell migration. They are also developing new video methods to study living cells in microscopes.

The research group is also responsibly for the daily running of the Core Facility for Advanced Light Microscopy at Oslo University Hospital. The facility gives other research groups in the Oslo region access to and guidance of the use of advanced microscopy equipment.

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Two of the speakers discussing with each other and laughing..

A café to advance T cell research

We want to accelerate cancer research in T cell immunotherapy!

In order to promote research collaboration, spread knowledge and exchange ideas, Oslo Cancer Cluster arranged a seminar together with Nature Research this week. The topic was T Cell Immunotherapy: Advances, Challenges and Future Directions.

What is T cell immunotherapy?

T cell immunotherapy is a rapidly growing area of research in cancer treatment. The research focuses on finding new ways to trigger the immune system to kill cancer cells.

The treatment method involves collecting T cells (a type of immune system cell) from a patient’s blood sample. The T cells are then modified in the laboratory so they will bind to cancer cells and destroy them.

One way to do this is called CAR T therapy. This involves adding a gene for a special receptor that binds to a specific protein (also called an antigen) on the patient’s cancer cells. The special receptor is called a chimeric antigen receptor (CAR). These cells are grown in large numbers in the laboratory and then infused in the patient to create an immune response.

Read more about CAR T cell therapies in this article from The National Cancer Institute

Image of researchers attending Nature Café on T cell immunotherapy in Oslo.

Many researchers attended the Nature Café for the opportunity to learn more about recent advances in T cell immunotherapy. Photo: Christian Tandberg

Why is cell therapy important?

Research into T cell immunotherapy is important, because it has the potential to treat and cure cancer. T cell immunotherapy can help cancer patients live longer and potentially has fewer side effects than traditional treatment methods, such as chemotherapy, radiation therapy and surgery.

However, more research is needed to make T cell immunotherapy work on all kinds of cancer. For example, some patients with haematologic cancer, cancers that develop in the blood-forming tissue, relapse into disease after treatment. Moreover, T cell immunotherapy does not work on all patients with solid cancer tumours yet.

Researchers wish to know why some cancers are resistant to T cell immunotherapy and why some patients acquire resistance to the treatment over time. Some patients also experience toxic side effects to T cell immunotherapy. Moreover, researchers are continually searching for possible new antigens (proteins) to target.

There are still many unanswered questions and that is why we need to accelerate the research.

Two researchers in the audience asking questions.

Members of the audience were eager to find out more about this rapidly growing area of research. Photo: Christian Tandberg

Why did we arrange this event?

The Norwegian research environment in cancer immunotherapy is world-class. But Norway is a small country and researchers need access to international partners and expertise to develop their findings.

The purpose of the event was to highlight recent findings in T cell immunotherapy. There was also the opportunity to discuss ongoing challenges and opportunities in the development of these types of treatments.

Among the guests were several prominent Norwegian cancer researchers, the pharma industry, hospital clinicians, biotech start-ups, and more. During the seminar, many of the participants in the audience asked follow-up questions and the café breaks were buzzing with conversations between researchers.

Three researchers in the audience discussing with each other.

The event was an opportunity to discuss with and learn from prominent researchers in the cell therapy field. Photo: Christian Tandberg

Watch the video below to see a few of the participants’ reactions:

Meet the speakers

The moderator for the event was Saheli Sadanand, Associate Editor, Research Manuscripts at Nature Medicine. Photo: Christian Tandberg

The moderator for the event was Saheli Sadanand, Associate Editor, Research Manuscripts at Nature Medicine. Photo: Christian Tandberg

 

The first speaker was Sara Ghorashian from the University College London

The first speaker was Sara Ghorashian from the University College London. Dr. Ghorashian is a consultant Paediatric Haematologist at Great Ormond Street Hospital for Children in London, and the co-investigator or lead UK investigator for six different CAR T cell clinical trials. She talked about her research to improve outcomes of CAR T cell therapy in patients with acute lymphoblastic leukemia. This is a type of cancer in the blood. Photo: Christian Tandberg

 

Attilio Bondanza, who is a physician-scientist and the CAR T cell program leader at Novartis Institutes of Biomedical Research in Basel, Switzerland.

The second speaker was Attilio Bondanza, who is a physician-scientist and the CAR T cell program leader at Novartis Institutes of Biomedical Research in Basel, Switzerland. Before joining Novartis, Dr. Bondanza was a professor at the San Raffeale University Hospital, where he led the Innovative Immunotherapies Unit. Dr. Bondanza talked about his work to model CAR T cell efficacy and CAR T cell-induced toxicities pre-clinically. Photo: Christian Tandberg

 

Sara Mastaglio, who is a physician scientist specialising in haematology at San Raffaele Scientific Institute, in Milan

The third speaker was Sara Mastaglio, who is a physician scientist specialising in haematology at San Raffaele Scientific Institute, in Milan. She has been actively involved in the development and clinical application of CAR T cell therapies. Dr. Mastaglio discussed her research on genome-edited T cells for the treatment of haematological malignancies. Photo: Christian Tandberg

 

Aude Chapuis, who is an assistant member of the Fred Hutchinson Cancer Research Center in Seattle

The last speaker was Aude Chapuis, who is an assistant member of the Fred Hutchinson Cancer Research Center in Seattle. In addition to running a lab, she sees patients as an attending physician at the Fred Hutch Bone Marrow Transplant Program at the Seattle Cancer Care Alliance. Dr. Chapuis discussed mechanisms of response and resistance to instruct next generations of T cell receptor gene therapy. Photo: Christian Tandberg

 

Want to find out more?

In February 2020, the journal Nature Research will publish an article with a more detailed overview of the speakers, their presentations and the research. We will provide a link here when it is available!

If you enjoyed this event, please subscribe to our newsletter to receive invitations to our upcoming events and a digest of our latest news.

 

We want to thank our sponsors for helping us make this event happen.

Sponsor logos: Novartis Oncology, ThermoFisher Scientific and Celgene

Torbjörn Furuseth, Targovax

New clinical trial at Oslo University Hospital

Our member Targovax has announced a new clinical trial for skin cancer patients at Oslo University Hospital.

The second part of a clinical trial for patients with refractory advanced melanoma (a type of skin cancer) will take place at Oslo University Hospital.

“We are excited that we can offer this treatment alternative to patients in our home country, and hopefully it will help us to recruit more patients faster,” said Torbjørn Furuseth, Chief Financial Officer, Targovax.

Targovax is a Norwegian biotech company that develops oncolytic viruses called ONCOS-102 to destroy cancer cells. The treatment is targeted towards solid tumours that are especially hard to treat. The ultimate goal is to activate the patient’s immune system to fight cancer.

Promising results

“The trial is until now conducted at three top hospitals in the US, where competition for patients to clinical trials is high. Oslo University Hospital is also a great cancer center, and currently there are no trials offered to this patient population,” said Furuseth.

Three out of nine patients responded to the treatment during the first part of the clinical trial. This included one complete response and two partial responses.

Dr. Magnus Jäderberg, CMO of Targovax, said: “It is promising to see this level of clinical responses after only three ONCOS-102 injections, including a complete response, which is rare in this heavily pre-treated patient population.”

A forceful combination

The treatment involves a combination of an oncolytic virus and an anti-PD1 checkpoint inhibitor.

The oncolytic virus is a modified virus that has been developed to selectively attack and kill cancer cells. You can read more about the oncolytic viruses on Targovax’s official website.

The anti-PD1 checkpoint inhibitor disrupts the interaction between proteins on the surface of cancer cells. This stops the cancer from evading the immune system.

“Earlier this year, we decided to expand the trial to test a more intensified schedule of ONCOS-102, and it will be interesting to see whether this regimen can generate more and deeper clinical responses,” said Dr. Alexander Shoushtari, Principal Investigator, Memorial Sloan Kettering Cancer Centre, New York.

The second part of the clinical trial is currently enrolling new patients.

 

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Jon Amund Kyte at the Norwegian Radium Hospital.

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.