Hakan Köksal has researched new designs of cells to improve cancer treatment. He defended his PhD via a digital platform from Oslo Cancer Cluster Incubator, due to corona restrictions.

Designing cells to fight cancer

How can new designs of T cells improve cell therapy for cancer patients?

Hakan Köksal defended his PhD digitally from Oslo Cancer Cluster Incubator.

Hakan Köksal defended his PhD digitally from Oslo Cancer Cluster Incubator.

This was the question Hakan Köksal attempted to answer in his PhD thesis, which he defended from the Oslo Cancer Cluster Incubator via a digital platform on Thursday 28 May 2020.

Köksal first arrived at Oslo Cancer Cluster Incubator to begin his PhD in October 2016 for the Department of Cellular Therapy, belonging to Oslo University Hospital. Three and a half years later, he is finally finished and has made a discovery that could potentially help cancer patients that are not responding to standard cell therapies.

“Essentially, what we are doing is called adoptive T cell therapy. We try to manufacture designs of chimeric antigen receptors to redirect T cells against cancer cells,” Köksal explained.

Cell therapy is an exciting, new area in cancer research and is a type of immunotherapy. This means that the patient’s immune system is changed in order to recognise and destroy the cancer cells in the body. CAR T cell therapy (CAR is short for chimeric antigen receptor) specifically involves collecting cells from the patient’s blood and changing them in the laboratory.

“We collect T cells, or lymphocytes, from the patients and engineer them so they can detect cancerous cells. Afterwards, they can be reinfused in the patient to destroy the cancer cells.” Hakan Köksal

Novel designs and new approaches

Current CAR T cell therapies have proved successful against several haematological cancers (blood cancers). However, the long-term clinical effects are quite limited and several barriers remain to cure all cancers with cell therapy. One problem Köksal looked at is when lymphoma patients treated with CD19 CAR T therapy relapse with CD19 negative lymphoma.

“We come up with alternative designs and approaches that may have an improved therapeutic effect, a lowered toxicity and improved survival in the body,” Köksal said. “The study we conducted can potentially be used as a standalone therapy or it can be complementary to reduce relapse.”

Standard CAR T therapies use antibody fragments as recognition units to detect cancer cells. In his thesis, Köksal has used a T cell receptor part, which is a different recognition domain, to increase the number of the targetable markers on cancer cells.

“Usually CAR T therapies can only detect proteins on the surface of the cell, but this new design can technically also recognise proteins inside the cell.” Hakan Köksal

Köksal stresses that we cannot know the clinical efficacy of the study before testing it in humans. The furthest they have tested is in mice, which is still a completely different organism from humans.

Read more about the research in this article: “The first Norwegian CAR”

Presenting during corona

Köksal finished his thesis in August 2019 but has not had the opportunity to defend it until now. Due to the ongoing corona situation, he could not present the trial lecture and defence in a filled auditorium but had to make do with an empty room and a laptop.

“It’s completely different. Normally, I would be standing on a stage and looking the audience in the eyes to see if I do well or bad. Now, I couldn’t see the audience, because they couldn’t share their video screens. I could only see my opponents,” Köksal explained.

In March, the corona pandemic affected the researchers in the Incubator too, because there were difficulties getting the necessary deliveries as companies worldwide had limited personnel. The laboratory had to restrict the number of people coming in and meeting rooms were temporarily converted to offices to avoid shared office space. The Incubator never closed completely and stayed open with extra sanitation procedures in place, so that the important research could go on.

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.

A collaborative effort

Köksal emphasised that the research behind his PhD thesis has been a team effort. He is thankful to his supervisors at Oslo University Hospital, Else Marit Inderberg, Sebastien Wälchli and June Helene Myklebust, for helping him and giving important guidance during his projects.

It has also meant a lot for him to be a part of the Oslo Cancer Cluster Incubator, Innovation Park and the Oslo Cancer Cluster ecosystem.

“It is good to be in such a translational building. You have one part that has an arm in the clinic and at the same time you have pre-clinical research going on side-by-side with the private companies. You have different niches and you can meet a lot of people with different backgrounds and interests. It gives you new perspectives,” Köksal said.

Köksal thinks the Incubator is a calm, relaxing work environment and not super busy like many other research buildings, where there is a lot of competition going on. In the Incubator, the researchers are united by the common goal to accelerate cancer treatments.

“I feel happy when I see an announcement that a company has reached a new milestone, because it means someone is making an impact and a difference out there.” Hakan Köksal

Köksal will now begin a postdoctoral position and continue his ongoing research projects. He aims to work on the development of cell therapies and hopes to make new breakthroughs on the treatment of solid cancers in the future.

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Bjørn Klem, general manager, and Janne Nestvold, laboratory manager, are excited to continue developing Oslo Cancer Cluster Incubator and its infrastructure for cell therapy research.

Accelerating cell therapies against cancer

Björn Klem and Janne Nestvold celebrate that the Oslo Cancer Cluster Incubator has been nominated among Europe's 20 best incubators.

Oslo Cancer Cluster Incubator has received a grant from the City of Oslo, which will be used to develop the infrastructure for cancer cell therapies.

Oslo Cancer Cluster Incubator has received NOK 300 000 in 2020 from the City of Oslo for a project that will support the development of a type of cancer treatment, known as cell therapies (scroll down to the bottom of this page to read a definition for cell therapy). Different forms of cancer cellular therapies are being explored in the Incubator, including genetically modified immune cells.

Cell therapies have the potential to cure cancer and turn it into a chronic disease. More research is however needed to document the full potential of cell therapies.

Specialised cell laboratory facility

The project involves setting up a specialised facility, which will be used for pre-clinical research and development of cell-based medicinal products.

Oslo Cancer Cluster Incubator’s laboratories are currently used for the design of therapeutic cells and to assess the effectiveness and safety of these cells in pre-clinical testing.

The funding from the City of Oslo will enable Oslo Cancer Cluster Incubator to expand the laboratories with the appropriate infrastructure and equipment. The laboratories will support researchers and companies in their development of new cell-based therapies. The initiative is hopefully a first step to establish production of T cell therapies in Norway as part of building a viable health industry.

Janne Nestvold, laboratory manager at Oslo Cancer Cluster Incubator, will coordinate the project.

“The specialised facility enables the Incubator to contribute in the development of cancer cell-based therapies in a preclinical setting,” said Janne Nestvold.

Several research groups in the Incubator already focus on the development of cell therapies. Now, they will have access to dedicated spaces with much needed equipment.

Supporting public-private research collaboration

Oslo Cancer Cluster Incubator is located next to the Norwegian Radium Hospital, one of Europe’s leading cancer hospitals and a part of Oslo University Hospital.

The Incubator’s partnership with Oslo University Hospital is one-of-a-kind in Norway. Hospital research staff work side-by-side with researchers from private companies and exchange experiences in a collaborative setting. They are also connected, through Oslo Cancer Cluster, to a global network of key players in the cancer research field.

Bjørn Klem, general manager of Oslo Cancer Cluster Incubator, hopes the Incubator can further assist both hospital research staff and researchers from private companies to bring forward new treatments.

“The support from City of Oslo is much appreciated as it enables us to take this important field of cell therapy forward, by supporting commercialisation of the growing number of start-ups in this area. This will allow companies to grow in Norway and create jobs, supporting the vision of the Oslo Science City initiative,” said Bjørn Klem.

About the RIP funding

The regional innovation programme (RIP) for the Oslo region has funded a total of NOK 25 million for business development and innovation in 2020.

The goal of RIP is to strengthen the Oslo region’s international competitiveness in cluster- and network development, entrepreneurship, supplier development and commercialisation.

This year’s award had a special emphasis on the health sector, marked by the ongoing coronavirus pandemic. More than ever, it has become important to support the local innovation clusters and the Norwegian health start-up companies.

 

DEFINITION

CAR T-cell therapy is a type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they more effectively will attack cancer cells. T cells are a specific type of white blood cells taken from a patient’s blood. Then the gene coding for a receptor that binds to a protein on the patient’s cancer cells, is added to the T cell in the laboratory. The receptor is called a chimeric antigen receptor (CAR) and enable the patient immune system to better recognise and fight cancer cells. Large numbers of the CAR T cells are then grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is approved for treatment of some cancer patients (leukaemia or lymfoma) and is studied in the treatment of many other types of cancer with promising effects.
Source: National Cancer Institute

 

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Bjørn Klem, general manager of Oslo Cancer Cluster Incubator, Arild Kristensen, general manager of Smart Care Cluster, and Kathrine Myhre, CEO of Norway Health Tech, look forward to developing the first Norwegian Health Catapult Centre.

Preparing for the first Health Catapult Centre

Bjørn Klem, general manager of Oslo Cancer Cluster Incubator, Arild Kristensen, general manager of Smart Care Cluster, and Kathrine Myhre, CEO of Norway Health Tech, look forward to developing the first Norwegian Health Catapult Centre.

Three leading Norwegian health innovation clusters will collaborate on forming a concept for the first Norwegian Health Catapult Centre.

Siva has selected Oslo Cancer Cluster Incubator, Norway Health Tech and Norwegian Smart Care Cluster to proceed to the next round of the Norwegian Catapult call. The three health clusters are now joining forces to apply for a Health Catapult Centre focusing on precision medicine, patient-centric innovation and health services, medical technology and digital health.

The purpose of a Catapult Centre is to support innovative small to medium-sized companies in Norway on their journey to reach the market. A Catapult Centre helps companies to develop prototypes, test, verify, visualise and simulate – so that ideas can be developed faster, better and with less risk.

By inviting the three health clusters to apply together for a Health Catapult Centre, Siva has shown that health innovation and industrialisation is a crucial part of Norwegian industry and trade. This supports the government’s White Paper on the Health Industry , which calls for the building of a strong Norwegian health industry. The current corona pandemic has also highlighted the importance of local health innovation providers and supporting Norwegian early-stage health companies that can quickly deliver solutions to big societal challenges.

The initial application was submitted last December and deemed successful in February. The main topics of precision medicine, patient-centric innovation and health services, medical technology and digital health will now be discussed further over the next six months in the planning of the final Catapult application. The managers of the three clusters look forward to the opportunity of developing a Health Catapult Centre together.

“By joining forces with two strong complementary Norwegian health clusters, we will strengthen the Catapult application by covering a broader range of services to Norwegian health start-ups and scale-ups. A successful application will enable Oslo Cancer Cluster Incubator to support the growth of Norwegian healthcare start-ups together with public healthcare institutions and international industry,” said Bjørn Klem, general manager of Oslo Cancer Cluster Incubator.

“One of the future key factors for the health industry in Norway to scale in the Norwegian and global market, will be to get access to tools, solutions, data and competence to develop, simulate, test, verify and produce their health products and solutions. The aim of the Health Catapult Centre will be to provide the health industry with these services and collaborative partners for the industry to scale. With the Health Catapult Centre up and running, Norway will also be an attractive partner to international health industry, that needs testing and clinical trials for them to launch new health products and solutions on the global market,” said Kathrine Myhre, CEO of Norway Health Tech.

“Together we stand, divided we fall. The three clusters now have an unique opportunity to provide the booming health industry in Norway with tools and services that will speed their development with higher quality, thus enabling world class solutions faster,” said Arild Kristensen, general manager of Norwegian Smart Care Cluster.

The final application for the Health Catapult Centre will be submitted this autumn. If successful, Oslo Cancer Cluster Incubator, Norway Health Tech and Norwegian Smart Care Cluster will jointly become the first Norwegian Health Catapult Centre.

logos

A kick-off meeting for the collaboration project was held at Oslo Cancer Cluster Incubator. In the image (from left to right): Hanna Rickberg and Jeanette Jansson from Swedish Academy of Pharmaceutical Sciences, Marie Svendsen from LMI, Bjørn Klem from Oslo Cancer Cluster Incubator.

Accelerating learning in Nordic life science milieus

Nordplus collaboration work group at kick-off in OCC Incubator

A new collaborative project will make life science learning more accessible in the Nordics and give a boost to innovation and medical development.

The Nordic life science industry is booming and medical developments have never been this rapid. Nonetheless, in small countries like the Nordics, educational resources may not always be easy for the life science community to access. Now, five Nordic life science organisations from Sweden, Finland and Norway have joined forces to improve learning across borders.

“Each of us are small countries, through this collaboration we can provide more high-quality learning opportunities for Life Science professionals and for a broader Nordic-Baltic target group, instead of reinventing the wheel,” says Hanna Rickberg, Head of Education at the Swedish Academy of Pharmaceutical Sciences.

As part of the Nordplus Horizontal programme, educational events, training workshops and practical courses directed towards the life science industry will be made available online. The life science professionals can participate via a live video stream or pre-recorded material, making learning accessible to those on-site or on remote locations and in other countries.

The five partners in the project are:

“Life science is a global business and cross-border collaboration is important, in particular for small countries in the Nordics,” says Bjørn Klem, General Manager at Oslo Cancer Cluster Incubator.

The project has received support from Nordplus to facilitate the sharing of educational resources across national borders in the Nordics. This will act as an innovation boost to Nordic life science environments.

“We are intrigued by the opportunity to explore how we can establish synergies across the Nordic markets when it comes to meeting educational needs within the Life Science sector. The underlying assumption is that the needs are similar. Networking for future collaboration may present as a secondary benefit,” says Dag Larsson, Senior Policy Manager, LIF – the Research Based Pharma Industry in Sweden.

Nordic cooperation will be paramount to make the most of medical advances and to make personalized medicine a reality.

“We see Nordic cooperation as an essential value to the medical development that is now taking place with both personalised medicine and building a life science industry across the Nordic countries,” says Marie Svendsen Aase, Communications Adviser, Legemiddelindustrien (LMI).

The project will run until 30 April 2021 and the five partners will share their courses via their websites and social media channels.

“Nordplus collaboration provides us with an excellent opportunity to expand our training services to the Nordic market and to share knowledge with the other partners,“ says Anja Isoaho, Training Manager at Pharmaceutical Information Centre (Finland).

 

Next upcoming activity in the Nordplus course plan 2020-2021:

The 4th Nordic RWE Conference 2020, 11 February 2020, 09:00-17:00, arranged by LMI in Kaare Norum Auditorium, Oslo Cancer Cluster Innovation Park, Ullernchausseen 64, 0379 Oslo. This event will be streamed.

 

Nordic Life Science Learning logo

 

Partner logos:

Lääketietokeskus logo

LIF logo

 

Läkemedelsakademin logo

 

LMI logo

 

OCC Incubator logo

Thomas Andersson, Business Development Adviser in Oslo Cancer Cluster Incubator, is one of the health mentors in the new scheme from Innovation Norway to help health startups to grow.

Find your health mentor

Thomas Andersson, Senior Adviser, Business Development, Oslo Cancer Cluster Incubator

Oslo Cancer Cluster Incubator has joined a new national health mentor program to help Norwegian startups connect with the right experts.

Are you a health startup? Do you need help to get going? Eight health clusters and incubators have joined forces to provide mentors and specialist knowledge to Norwegian health startups, through the new health mentor program from Innovation Norway. One of them is Oslo Cancer Cluster Incubator.

Bjørn Klem, general manager of Oslo Cancer Cluster Incubator, commented:

“Innovation Norway’s new health mentor program is a good scheme for startups that need help to establish their company. Access to a network of health mentors give the companies the opportunity to get tailor-made guidance in a very challenging development phase.”

This is the first time Innovation Norway offers a mentor program for a specific industry. The scheme is a pilot project for year 2020. Bård Stranheim, responsible for the mentor program in Innovation Norway, said:

“Good mentors are an important key to growth. This scheme will give high-quality mentors. Maybe this pilot project will be the basis of a new model to connect world-class mentors with Norwegian startups to prepare them for international growth.”

 

The health mentor program consists of:

 

Apply on Innovation Norway’s website for a health mentor

 

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From the left: Bjørn Klem, General Manager, and Janne Nestvold, Laboratory Manager, are thrilled that their incubator is among Europe’s top 20 biotech start-up ecosystems.

Among Europe’s finest 

Björn Klem and Janne Nestvold celebrate that the Oslo Cancer Cluster Incubator has been nominated among Europe's 20 best incubators.

OCC Incubator was recently rated among the top 20 European biotech incubators. Here’s why!

Every year, the biotech website Labiotech makes a top 20 list of the best biotech incubators in Europe. Oslo Cancer Cluster (OCC) Incubator is the only Norwegian incubator on the list this year, together with well established incubators in Belgium, Switzerland, Great Britain, Germany, Sweden and other European countries.

Labiotech.eu is the leading digital media covering the European biotech industry, with over 150,000 visitors every month.

Size and relevance matters

We asked Clara Rodríguez Fernández, Senior Reporter in Labiotech, about the selection criteria. She replied:

“We aim to include the most relevant incubators across different European countries. We selected those based on their size and relevance within their country’s biotech ecosystem and also based on feedback from the industry contacts we sent our preliminary list to.”

See the full top 20 list on labiotech.eu.  

Means a lot in Norway

In Norway, the list has attracted attention.

“This means a lot. We have a strong and attractive ecosystem around Oslo Cancer Cluster on research and commercialization of pharmaceuticals. The latest success story is the tech company OncoImmunity that was bought by the tech giant NEC this summer.” Håkon Haugli, CEO Innovation Norway

Read more about NEC OncoImmunity in this news story.

Håkon Haugli continues:

“We also recognize that Norway, through Oslo Cancer Cluster, is positioned very well for the European Union’s next big endeavour, ‘Missions’, which will be launched next year. Cancer is one of five focus areas, which the European Union will channel considerable project resources into, to resolve one of our time’s big societal problems.”

The European Union has defined five research and innovation mission areas, inspired by the Apollo 11 mission to put a man on the moon. The missions aim to deliver solutions to some of the greatest challenges facing our world, such as cancer, climate change, healthy oceans, climate-neutral cities and healthy soil and food.

You can read more about the European research and innovation missions on this official website.

A boost of motivation

For OCC Incubator, being on the top 20 list is a nice boost of motivation. Bjørn Klem, General Manager OCC Incubator, puts it this way: 

“We are excited about being rated among the best biotech incubators in Europe. It motivates us to become the most attractive space for innovations in the field of cancer!” 

 

Want to read more about biotech incubators and start-up opportunities? 

 

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A new project will make continuous learning for life science professionals easier by facilitating courses and material digitally. Illustration photo: Emma Dau on Unsplash

Cross-border courses in the Nordics

Two women working on two laptops and smiling.

Oslo Cancer Cluster Incubator collaborates with partners in Sweden, Norway and Finland to help life science professionals learn from their neighbours.

“Life science is a global business and cross-border collaboration is important, in particular for small countries in the Nordics” says Bjørn Klem, manager at Oslo Cancer Cluster Incubator.

Bjørn Klem, manager of Oslo Cancer Cluster Incubator.

Bjørn Klem, manager of Oslo Cancer Cluster Incubator.

Together with partners from three different professional sectors in three countries, Oslo Cancer Cluster Incubator recently received €75,000 in project funding over two years from the Nordplus Programme.

Digital competences

Nordplus is the Nordic Council of Ministers’ most important programme in the area of lifelong learning. On its webpage, Nordplus writes that more than 10,000 people in the Nordic and Baltic region benefit from the programme every year.

In 2019 and 2020, Nordplus welcomes applications on digital competences and computational thinking.

Innovation and competition

Bjørn Klem hopes that the project will benefit both Nordic innovation and competition.

“The outcome of this project should be to share educational resources to increase competence in the Nordic innovation environments. This will make innovation in life science more competitive in the global market.” Bjørn Klem

The Association of the Pharmaceutical Industry in Norway (LMI), one of the five partners in the project, also stresses the importance of Nordic collaboration for the life science industry. Marie Svendsen Aase, project coordinator LMI, puts it this way: 

“We see Nordic cooperation as an essential value to the medical development that is now taking place with both personalised medicine and building a life science industry across the Nordic countries.”

Learning across the region

The project will make continuous learning for life science professionals, specifically in pharmaceuticals and medical devices, easier by facilitating courses and material digitally. At the same time, the project aims to adapt national courses to a Nordic and Baltic audience.  

A course plan will be made in 2019.

The five partners in the project are:

  • Swedish Academy of Pharmaceutical Sciences
  • Swedish Pharmaceutical Industry Association
  • Pharmaceutical Information Centre in Finland
  • The Association of the Pharmaceutical Industry in Norway (LMI)
  • Oslo Cancer Cluster Incubator

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

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.

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

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

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

 

 

What is a CAR?

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

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

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

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

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

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

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

 

Made in Norway  

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

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

“Even the mouse was Norwegian.” Hakan Köksal

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

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

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

 

The first CAR-therapy

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

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

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

 

Not effective for all

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

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

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

Dr. Pierre Dillard and Hakan Köksal are part of the team behind the new study on CD37CAR T-cell therapy for treatment of B-cell lymphoma.

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: 

 

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'.

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

One of the tenants in the Oslo Cancer Cluster Incubator.

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

 

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

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

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

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

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

 

Office plan of the OCC Incubator

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

 

A unique model

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

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

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

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

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

 

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

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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