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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.

 

 

 

 

Doctor examining the birthmark of a female patient

Promising start for expansion group of Targovax clinical trial

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.

Hands cradling female reproductive system

New collaboration aims to treat cervical cancer

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.

 

 

Immunotherapy: Finding the Right Fit

A new Norwegian research collaboration helps uncover what treatments are the right fit for American cancer patients. Who are the collaborators and what are they doing?

There’s a lot of excitement and optimism concerning immuno-oncology, where the method is to utilize a person’s own immune system to treat cancer. However, excitement aside, methods such as this are often a costly experience, in expenses as well as negative and unpredictable side-effects for the person in treatment.

Calibrated Collaboration
Company OncoImmunity is collaborating with the Norwegian Cancer Genomics Consortium (NCGC) in finding out what is causing these serious and unpredictable side-effects.

– This collaboration is an exciting opportunity for us. This is because we can demonstrate the strength of our advanced bioinformatics tools and show how they can be used to detect combinations of genetic variation in the patient, as well as neoantigens in the tumour that can further be used as biomarkers for sensitivity to this type of cancer treatment, says Dr. Richard Stratford, CEO of OncoImmunity, in a recent press release.

OncoImmunity develops proprietary machine-learning software for personalized cancer immunotherapy. The company previously won a prestigious European grant for their work.

You can read about it here!

Patients with sarcomas
The researchers in the collaboration analyse the patient’s genes in the tumour. More specifically, they are looking at American patients by using pembrolizumab, a humanized antibody that blocks cancer protection, on patients with sarcoma – cancer in various binding tissues.

Sarcomas are a rare form of cancer where treatment for such procedures have not developed as much as other cancer treatments. Patients who have sarcoma have generally a worse prognosis than other groups.

The research will be shared with the organization Sarcoma Alliance for Research through Collaboration (SARC), helping researchers within the organization to better utilize the results.

The NCGC perspective
The NCGC has, with help from the Norwegian Research Council, established a platform for advanced analysis for such cases. On top of this, they have a vast network of expertise within the area of molecular oncology.

– We find it exciting to see better treatments that can work for multiple cancers where treatment provides promising results, despite limited response, says Professor Ola Myklebost, leader for NCGC and the research project, in a recent press release.

– It is important to be able to choose the right patients for the right treatments. Not only because the treatment is high in cost, but also because of the serious and negative side-effects, he adds.

How Cancer Research Becomes a Company

The Department of Cellular Therapy is great at transforming cancer research into new companies. The latest spin-out is Zelluna.

 

The Department of Cellular Therapy at the Radium Hospital, Oslo University Hospital, features one of Europe’s largest and most modern good manufacturing practice (GMP) facilities for cellular products. Head of the department is Prof. Gunnar Kvalheim. They are also conducting translational research, and their research has been spun out as several companies, such as the newly established company Zelluna.

The immunomonitoring unit is a major part of the department, and is led by Else Marit Inderberg. This unit is situated in the Oslo Cancer Cluster Incubator, which is an integrated part of the Oslo Cancer Cluster Innovation Park. A translational research lab has been created and is associated to the immunomonitoring unit.

The cancer killer
“Our major strength is that we have all aspects within the department to take cellular research from the bed to bench and back again. We have the equipment and the specialists to do everything here”, says Inderberg.

Together with Sébastien Wälchli, she is also the project leader for the translational research lab. Here, they develop cancer vaccines and work with adoptive T cell therapy. A T cell, or T lymphocyte, is a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated immunity. T cells have the capacity to kill cancer cells.

In the lab, they look for a T cell receptor (TCR), which is a molecule found on the surface of T cells. They use Chimeric antigen receptors (CARs), which are engineered receptors that graft an arbitrary speci city onto a T cell. Ultimately, the researchers work with a universal cell line for cellular therapy – a universal cancer killer.

This is a T cell, or more precisely, an actin cytoskeleton of a T lymphocyte. The picture is obtained by a special micro- scope. The cell’s size: 38*38 μm. Photo: Pierre Dillard

Innovation from the biobank
“In the translational research lab, we think innovation all the time. In our research, we actively search for solutions to unmet medical needs within cancer”, says Inderberg.

The translational research lab was built upon the work done by the section for immunotherapy established by professor emeritus Gustav Gaudernack, and most of its activity relies on the use of a database of patient samples called the biobank. This specific biobank represents an inestimable source of information about the patients’ response to immunological treatments over the years. Furthermore, the patient material can be reanalysed and therapeutic molecules isolated. This is the basis of the company Zelluna.

Industrial collaborations
The Department of Cellular Therapy is heavily involved in both academic and industrial collaborations. The latter include collaborations with several biotech companies as well as pharma companies situated in the Oslo Cancer Cluster Innovation Park, developing novel immunotherapy cancer treatments. Examples of industrial collaborations are the German company Medigene, the Norwegian biotechs Targovax, Ultimovacs, Lytix and PCI Biotech, and the bigger biopharmaceutical companies BMS, Novartis and ThermoFisher.

In addition to their industrial collaborations, the Department of Cellular Therapy also wants to commercialise their own projects.

The Zelluna Spin-out
“Our latest spin-out is Zelluna, which has recently been set up as a start-up. Staff has just been hired to drive the development of TCR-based therapies to clinical trials”, says Sébastien Wälchli.

The TCR-approach is based on identication of T cell receptors from patients clinically benefitting from treatment with vaccines from back in the nineties and early 2000s. The approach is to modify the patient T cells to express the same receptors before giving the cells back to the patients, ready to combat the cancer cells.

The company has been established through the efforts of the Radium Hospital Research Foundation as well as Inven2.

“This is a very interesting and unique approach. We are eagerly anticipating the development of the company”, says Inderberg.

How Our Genes Will Change Cancer

Doctors, researchers and audience gather at breakfast to learn about genetics, data and how working together will help beat cancer.

The time is 8:15. Many have started to file in and shuffle to their seats while chatting and occasionally sipping their first morning coffee. As it starts to quiet down, the lights are dimmed, the audience wake up and the breakfast meeting begins.

An air of seriousness with a hint of respect changes the atmosphere, and the audience watches as the first guest speaker steps in and introduces the concept of genes and their relation to cancer.

– Cancer is brought on by errors in our genes. Most of the time, cancer is a result of the unlucky, says Borge, who is the director at the Norwegian Biotechnology Advisory Board.

This is the start of his talk on genes and cancer, where the audience is introduced to that which defines us most: DNA, the molecule of life.

To the moon and back
– 20,310 recipes in our genetic material. 2 meters of DNA in every cell. 10 Billion cells, of which 20 billion meters of DNA is found. If you do the math, astonishingly it amounts to 26,015 trips back and forth to the moon, Borg says, as he shows us a visual representation on the powerpoint slide. (See video in Norwegian.)

It’s this incredibly long strand of genetic material where things can go horribly wrong. If there’s a genetic error, or mutation in the DNA that happens to take place between the double helix and if there’s enough errors, cancer happens. This is the unfortunate fate for many of us.

– However, we may not have come a long way in finding the ultimate cure for cancer, but what we have accomplished is the ability and possibility of analysing, and ultimately predicting, cancer through genome sequencing, Borge says.

It was the best of times…
This message, as a central theme to the breakfast meeting taking place, shines a hopeful light in an otherwise frightful and serious subject. With genome sequencing, or list of our genes, scientists and doctors will have greater accuracy to predict genes that are potential carriers, and highly susceptible to, different cancers.

However, this requires a large amount of genome sequences: we need an army of genome data.

From terminal to chronic
To set further example, the next speaker to take the stage is oncologist Odd Terje Brustugun. He stresses the importance of personalized treatment for lung cancer patients, even those with metastatic cancers. These patients can be tested today to see if they are viable to receive new kinds of treatmemt, such as targeted therapy. This was the case for lung-cancer patient, and survivor for five years, Kari Grønås.

Kari Grønås was able to participate in a clinical study. She was treated with targeted therapy instead of the ordinary treatment for lung cancer patients at that time: chemotherapy.

– I feel I have gone from feeling like I have a terminal disease to a chronic one, she says from the podium.

Beating cancer: the story of us
This personalized approach is arguably what worked for Kari, setting the example and potential for the future. If we can analyse our own genes for potential cancer, then we are both able to prevent and provide personalized medicine catered to the individual. This is why genome sequencing is important for the future.

However, this cannot be done alone. To get a representable treatment for the individual, we need data. And data does not come reliably from one individual, but from the many.

– It is not your genes that are the key for tomorrows cancer research, it is ours. It is collaboration where large amounts of data and correlation will give us the knowledge that ensures the right path towards the future. A future with better cancer treatment for all, says Ole Johan Borge.