Cancer Crosslinks 2020 gathered a distinguished group of national and international speakers, and received a record number of meeting delegates.

Cancer Crosslinks 2020

The speakers, chairpersons, introducers and organizers of Cancer Crosslinks 2020Oslo Cancer Cluster

Engaging presentations by leading international and Norwegian oncology experts at the 12th Cancer Crosslinks “Progress in Cancer Care – A tsunami of promises or Game Changing Strategies?”.

Oslo Cancer Cluster’s annual meeting gathered more than 350 delegates from all over Norway at the Oslo Cancer Cluster Innovation Park, and more than 50 participants followed the live stream. The record high participation shows the large interest in translational cancer research and the importance of the programme for the Norwegian oncology community.

Cancer Crosslinks has become one of the largest national meeting places for oncologists, haematologists, translational researchers, regulatory experts and industry representatives. The meeting offers a full day educational program.

The aim of the conference is to stimulate broader interactions between researchers and clinicians, to encourage translational and clinical research, and to inspire collaborations. Novel partnerships between industry, academia and authorities are essential to deliver new treatments and diagnostics to Norwegian cancer patients.

“At the start of 2020, cancer patients have more treatment options than ever before. Immuno-oncology is firmly established as the fourth pillar of cancer treatment and the tremendous progress in the field is reflected in increased survival rates,” said Jutta Heix, Head of International Affairs, Oslo Cancer Cluster. “However, many patients do not benefit from novel treatments and we still have significant gaps in our understanding of the complex biological mechanisms. Deciphering this complexity is a task for the decade to come. The Cancer Crosslinks 2020 speakers are shedding light on emerging concepts and key challenges and discuss how they are addressing them to advance cancer care.”

The audience at Cancer Crosslinks 2020.

The audience at Cancer Crosslinks 2020. Photo: Cameo Productions UB/Oslo Cancer Cluster

An inspiring programme

Referring to a record number of new oncology drug approvals in recent years and an enormous global pipeline of drugs in late-stage development, this year’s programme addressed the question “Progress in Cancer Care – A Tsunami of Promises or Game-Changing Strategies?”. Distinguished international experts from leading centres in the US and Europe presented emerging concepts, recent progress and key questions to be addressed for both solid and haematological cancers.

Cancer researchers and clinicians from all of Norway enjoyed excellent presentations and engaging discussions with speakers and colleagues.

“Cancer Crosslinks 2020 gave me an opportunity to listen to talks by international top scientists, and discuss some of the latest developments in translational cancer research with meeting participants from academia and industry in a relaxed and inspiring setting,” said Johanna Olweus, Head of Department of Cancer Immunology at the Institute for Cancer Research.

“Cancer Crosslinks is always a meeting that makes me proud of being part of Oslo Cancer Cluster. It is inspiring to see Norwegian and international participants come together to discuss recent progress in cancer research and how to develop cancer treatments for the patients,” said Øyvind Kongstun Arnesen, Chairman of the Board, Oslo Cancer Cluster.

The day programme was complemented with an evening reception in the city center where speakers and delegates continued their lively discussions and listened to an inspiring talk by Ole Petter Ottersen, President of Karolinska Institute, at Hotel Continental in Oslo.

Cancer Crosslinks was established by Oslo Cancer Cluster in 2009 in collaboration with the pharmaceutical company Bristol-Myers Squibb.

“Cancer Crosslinks 2020 has been a fantastic conference, where the presenters have given an excellent description of current and near future achievements within cancer research and the importance of understanding the underlying biology of cancer to rationally give patients the correct cancer therapy. In particular within immunotherapy, there is a need to understand the dynamic complexity of tumor immunology and how to apply the best and tailored immuno-oncology based treatment strategy for cancer patients,” said Ali Areffard, Disease Area Specialist Immuno-Oncology, Bristol-Myers Squibb.

This year, the pharmaceutical company Sanofi Genzyme Norway was a proud co-sponsor of the meeting.

“It was great to be able to provide a platform for interaction between the Norwegian scientific cancer environment and top international research capacities. Therefore, it was with huge enthusiasm Sanofi Genzyme co-sponsored this important conference. New treatment options in oncology are developing fast, where new treatment modalities provide clinicians with additional and superior options. New treatments specifically targeting the malignant cells, as well as activating the host immune response towards the cancer, provides tools to significantly improve current cancer treatments. This year’s Cancer Crosslinks conference gave an excellent insight into this,” said Knut Steffensen, Medical Advisor Hematology Nordic & Baltics, Sanofi Genzyme.

Interview with Prof. Jason Luke

View the interview with Prof. Jason Luke, by HealthTalk, in the video below:

Interview with Prof. Michel Sadelain

View the interview with Prof. Michel Sadelain, by HealthTalk, in the video below:

The speakers at Cancer Crosslinks 2020

Jason J. Luke, Director of the Cancer Immunotherapeutics Center, Associate Professor of Medicine, University of Pittsburgh Medical Center and Hillman Cancer Center

Jason J. Luke, MD, FACP, Director of the Cancer Immunotherapeutics Center, Associate Professor of Medicine, University of Pittsburgh Medical Center and Hillman Cancer Center, USA. Photo: Cameo UB Productions/Oslo Cancer Cluster

Stefani Spranger, Howard S. and Linda B. Stern Career Development Assistant Professor, Koch Institute for Integrative Cancer Research at MIT, Cambridge

Stefani Spranger, Howard S. and Linda B. Stern Career Development Assistant Professor, Koch Institute for Integrative Cancer Research at MIT, Cambridge, USA. Photo: Cameo UB Productions/Oslo Cancer Cluster

Harriet Wikman, Professor, Group Leader, Center for Experimental Medicine, Institute of Tumor Biology, University Medical Centre Hamburg-Eppendorf

Harriet Wikman, Professor, Group Leader, Center for Experimental Medicine, Institute of Tumor Biology, University Medical Centre Hamburg-Eppendorf, Germany. Photo: Cameo UB Productions/Oslo Cancer Cluster

Vessela Kristensen, Professor, Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital

Vessela Kristensen, Head of Research and Development and Director of Research at the Dept. of Medical Genetics, Oslo University Hospital, Norway. Photo: Cameo UB Productions/Oslo Cancer Cluster

Peter A. Fasching, Professor of Translational Gynecology and Obstetrics, University Hospital and Comprehensive Cancer Center Erlangen-EMN

Peter A. Fasching, Professor of Translational Gynecology and Obstetrics, University Hospital and Comprehensive Cancer Center Erlangen-EMN, Germany. Photo: Cameo UB Productions/Oslo Cancer Cluster

Karl Johan Malmberg, Professor, Group Leader Dept. of Cancer Immunology and Director STRAT-CELL, Oslo University Hospital, Norway.

Karl Johan Malmberg, Professor, Group Leader Dept. of Cancer Immunology and Director STRAT-CELL, Oslo University Hospital, Norway. Photo: Cameo UB Productions/Oslo Cancer Cluster

Michel Sadelain, Director, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center

Michel Sadelain, MD, PhD, Professor, Director, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, USA. Photo: Cameo UB Productions/Oslo Cancer Cluster

Bjørn Tore Gjertsen, Consultant Hematology, Haukeland University Hospital, Norway.

Bjørn Tore Gjertsen, Professor of Hematology, Centre for Cancer Biomarkers CCBIO, Dept. of Clinical Science, University of Bergen, Norway. Photo: Cameo UB Productions/Oslo Cancer Cluster

Hermann Einsele, Professor, Chair, Dept. of Internal Medicine II, Head of the Clinical and Translational Research Program on Multiple Myeloma, Wuerzburg University Hospital

Hermann Einsele, Professor, Chair, Dept. of Internal Medicine II, Head of the Clinical and Translational Research Program on Multiple Myeloma, University Hospital Wuerzburg, Germany. Photo: Cameo UB Productions/Oslo Cancer Cluster

 

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The High Throughput Screening Lab at SINTEF. Photo: Thor Nielsen / SINTEF

SINTEF to develop methods in immuno-oncology

The Cell Lab at SINTEF. Photo: Thor Nielsen / SINTEF

SINTEF and Catapult Life Science are looking for new partners to develop methodology for cancer immunotherapy.

“We want to develop methods within immunotherapy, because this is currently the most successful strategy for improving cancer treatments and one of the main directions in modern medicine,” says Einar Sulheim, Research Scientist at SINTEF.

The Norwegian research organization SINTEF is an Oslo Cancer Cluster member with extensive knowledge in characterisation, analysis, drug discovery and development of conventional drugs.

The new project on methodology for cancer immunotherapy recently started in April 2019 and is a collaboration with Catapult Life Science, a new Oslo Cancer Cluster member. The aim is to help academic groups and companies develop their immunotherapy drug candidates and ideas.

Help cancer patients

Ultimately, the main aim is of course that the project will benefit cancer patients. Immunotherapy has shown to both increase life expectancy and create long term survivors in patient groups with very poor prognosis.

“We hope that this project can help streamline the development and production of immunotherapeutic drugs and help cancer patients by helping drug candidates through the stages before clinical trials.” Einar Sulheim, Research Scientist at SINTEF

 

Develop methodology

The project is a SINTEF initiative spending NOK 12,5 million from 2019 to 2023. SINTEF wants to develop methodology and adapt technology in high throughput screening to help develop products for cancer immunotherapy. This will include in vitro high throughput screening of drug effect in both primary cells and cell lines, animal models, pathology, and production of therapeutic cells and antibodies.

 

High throughput screening is the use of robotic liquid handling systems (automatic pipettes) to perform experiments. This makes it possible not only to handle small volumes and sample sizes with precision, but also to run wide screens with thousands of wells where drug combinations and concentrations can be tested in a variety of cells.

 

The Cell Lab at SINTEF. Photo: Thor Nielsen / SINTEF

The Cell Lab at SINTEF. Photo: Thor Nielsen / SINTEF

 

Bridging the gap

Catapult Life Science is a centre established to bridge the gap between the lab and the industry by providing infrastructure, equipment and expertise for product development and industrialisation in Norway. Their aim is to stimulate growth in the Norwegian economy by enabling a profitable health industry.

“In this project, our role will be to assess the industrial relevance of the new technologies developed, for instance by evaluating analytical methods used for various phases of drug development.” Astrid Hilde Myrset, CEO Catapult Life Science

A new product could for example be produced for testing in clinical studies according to regulatory requirements at Catapult, once the centre achieves its manufacturing license next year.

“If a new method is intended for use in quality control of a new regulatory drug, Catapult’s role can be to validate the method according to the regulatory requirements” Myrset adds. 

SINTEF and Catapult Life Science are now looking for partners.

Looking for new partners

Einar Sulheim sums up the ideal partners for this project:

“We are interested in partners developing cancer immunotherapies that see challenges in their experimental setups in terms of magnitude, standardization or facilities. Through this project, SINTEF can contribute with internal funding to develop methods that suit their purpose.”

 

Interested in this project?

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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