Gert W. Munthe, Chairman of the Board, and Øystein Rekdal, PhD, CEO of Lytix Biopharma. Photo: Håvar Haug

Lytix Biopharma signs licensing agreement

Our member Lytix Biopharma has entered into a milestone agreement with Verrica Pharmaceuticals to license the company’s lead drug candidate against skin cancer.

The Norwegian start-up Lytix Biopharma from Tromsø has reached a new milestone. The company has licensed its lead drug candidate LTX-315 against skin cancer to the dermatology therapeutics company Verrica Pharmaceuticals. Verrica Pharmaceuticals will develop and commercialize LTX-315 for dermatologic oncology indications.

The drug is a first-in-class oncolytic peptide-based immunotherapy. Immunotherapy is a type of cancer treatment that mobilises the patient’s own immune system to fight cancer. Peptides are short chains of between two and fifty amino acids that can have many different sources or functions. Peptides hold great potential for both cancer therapy and diagnostics, through the development of anticancer peptides, use of peptides for drug delivery, and cancer targeting.

Clinical studies have shown that the drug LTX-315 from Lytix Biopharma has the ability to kill human cancer cells and induce a specific anti-cancer immune response when injected locally into tumours.

“We are pleased to enter into this collaboration with Verrica, which has significant expertise within the field of dermatology” said Øystein Rekdal, CEO of Lytix Biopharma. “Our lead drug candidate, LTX-315, has shown very promising efficacy and safety signals in cancer patients during Phase I/II studies and we are excited that this partnership with Verrica will expand the applications for LTX-315”

The agreement entitles Lytix Biopharma to up-front payment, contingent regulatory milestones based on achievement of specified development goals, and sales milestones, with aggregate payments of more than $110M, as well as tiered royalty payments in the double-digit teens once Verrica successfully commercializes LTX-315 in dermatologic oncology indications.

Lytix Biopharma and Oslo Cancer Cluster

Lytix Biopharma has been a part of the innovation environment in Oslo Cancer Cluster Innovation Park since the building opened in 2015, utilising both offices and laboratory for research and development.

Oslo Cancer Cluster Incubator has offered the company its services in both private and shared laboratory spaces. In addition, Lytix Biopharma has been active in the animal laboratories at The Norwegian Radium Hospital (a part of Oslo University Hospital), which is located right next to the Incubator.

The researchers in Lytix Biopharma have gained their PhDs in the Incubator, in collaboration with its innovation environment. One of the company’s former researchers is now the laboratory manager in the Incubator.

“This shows how the innovation environments enrich one another in a positive sense, by sharing access to different services and thanks to the power of our geographic location,” said Bjørn Klem, general manager of Oslo Cancer Cluster Incubator.

Lytix Biopharma recently moved out of the Incubator after finishing their main project earlier this year and remains a member of Oslo Cancer Cluster.

Oslo Cancer Cluster Incubator is financed by SIVA, the Norwegian national infrastructure for innovation, consisting of incubators, business gardens, catapult centres, innovation enterprises, innovation centres and industrial real estate.

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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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Gustav Vik (to the left) from Kjellervolla school and Martin Dimov from Mailand school are collaborating in the laboratory to isolate T cells. Photo: Bente Prestegård.

Research talents learned about immunotherapy

Gustav Vik from Killevold school and Martin Dimov from Mailand school are enjoying the gatherings arranged by Talentsenteret for realfag: “This is very interesting because we are learning things that are not part of the curriculum and we like to learn about current topics.”

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

A group of talented science students from Oslo and Akershus spent two days learning about immunotherapy from former cancer researchers, who are now teachers at Ullern Upper Secondary School and researchers at Thermo Fisher Scientific.

Collaboration partners: Oslo Cancer Cluster, Thermo Fisher Scientific Norway, Ullern Upper Secondary School, Norsk teknisk museum (The Norwegian Museum of Science and Technology) and Oslo Vitensenters Talentsenter i realfag (Talent centre for the natural sciences)

In February, 25 students from 19 different schools in Oslo, which are a part of “Talentsenteret for realfag” (Talent Centre for the Natural Sciences), arrived together to Oslo Cancer Cluster Innovation Park and Ullern Upper Secondary School.

The students were there to participate in a specially tailored two-day programme about medical research and the use of immunotherapy to treat cancer.

The days were spent partly in a classroom to learn about the theory of the immune system and partly in a laboratory to learn how to isolate a type of cells in the immune system called T cells. The method the students learned about is used in modern cell therapies against cancer, which are called CAR T therapies.

Gustav Vik from Kjellervolla School and Martin Dimov from Mailand School are enjoying the gatherings arranged by Talentsenteret for realfag: “This is very interesting because we are learning things that are not part of the ordinary school syllabus and we like to learn about current topics.”

Kaja Flote from Hellerasten school is looking in the microscope to find T cells. She thinks it is exciting to learn more about the depth of the immune system and how it can be changed to fight cancer. Photo: Bente Prestegård.

Kaja Flote from Hellerasten School is looking in the microscope to find T cells. She thinks it is exciting to learn more about the complexity of the immune system and how it can be changed to combat cancer. Photo: Bente Prestegård.

The next day, the students visited the production facilities of Thermo Fisher Scientific Norway, located in Lillestrøm. This is where the company makes Dynabeads (also known as “Ugelstadkulene” in Norwegian) to be used in five billion diagnostic tests every year and in CAR T therapies against cancer.

The Norwegian TV channel TV2 has produced this news segment about Emily Whitehead (link in Norwegian), the first child in the world who received CAR T therapy to treat her cancer, which was deemed incurable. The segment was recorded in 2019, when Emily and her family visited the Norwegian employees at Thermo Fisher Scientific in Oslo. Emily is today 13 years old and has been cancer-free for over eight years.

You can read more about the students’ experience at Thermo Fisher Scientific in this article from 2017, when another group of students from Ullern Upper Secondary School visited the same production facilities.

The researcher Morten Fure from Thermo Fisher tells the students about Dynabeads, also known as “Ugelstadkulene”, CAR T therapy, immunotherapy, and cancer. He has prepared T cell solutions that the students will look at in the microscope. Photo: Bente Prestegård.

The researcher Morten Luhr from Thermo Fisher Scientific tells the students about Dynabeads (also known as “Ugelstadkulene”), CAR T therapy, immunotherapy, and cancer. He has prepared T cell solutions that the students will look at in the microscope. Photo: Bente Prestegård.

The background to the collaboration

“Talentsenteret i realfag” (link in Norwegian) is a customised educational option for students who are especially strong academically. It is for those students who find that the standard school curriculum does not challenge them enough. Just like the school adapts the teaching for students who need extra help in subjects, they adapt the teaching for students who already know a lot and want to learn even more. This is a group of students with a high degree of motivation and a hunger for knowledge that is extraordinary.

The centre employs experts in different subjects to give the students the academic challenges they need. That is why this two-day programme in medicine and immunotherapy was held in February.

The programme was developed by employees from Thermo Fisher Scientific and two teachers from Ullern Upper Secondary School. Fet and Flydal Jenstad both have backgrounds as cancer researchers at the Institute for Cancer Research and the Institute of Cancer Genetics and Informatics respectively. Fet and Flydal Jenstad share the responsibility for the new researcher programme at Ullern Upper Secondary School. Read more about the researcher programme here (link in Norwegian).

Oslo Cancer Cluster and Ullern Upper Secondary School have a school collaboration project since 2009. The goal is to contribute to educating the researchers and entrepreneurs of the future.

Thermo Fisher Scientific is a global biotech company with strong Norwegian roots through the acquisition of the Norwegian biotech Dynal. Thermo Fisher Scientific is one of the members of Oslo Cancer Cluster and actively participates in the school collaboration between Oslo Cancer Cluster and Ullern Upper Secondary School.

Read articles about the other school collaborations Thermo Fisher Scientific have participated in:

 

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Photo: Christopher Olssøn/Oslo Cancer Cluster

News from our members

There have been several exciting developments from our members over the last week. Here are three condensed news from the Norwegian biopharma sphere that we wish to highlight.

Promising combination treatment

Our member Targovax, a Norwegian immuno-oncology company, has announced some encouraging data from one of their clinical studies.

The study is directed towards patients with mesothelioma, a type of cancer that develops in the thin layer of tissue that covers many of the internal organs, for example the lining of the lungs or chest wall.

The patients are given a combination treatment consisting of Targovax’s own oncolytic virus called “ONCOS-102” and the standard of care: chemotherapy.

The preliminary data show a numerical advantage in progression-free survival for the patients that have received ONCOS-102. There has also been a robust immune activation in the experimental group. It has also been shown that the combination treatment is well tolerated by the patients.

Targovax are now in ongoing discussions with a pharmaceutical company about a prospective partnership in order to launch a checkpoint inhibitor combination study.

View the entire press release from Targovax

US patent for Norwegian cancer technology

Our member PCI Biotech, a Norwegian biopharmaceutical company, has secured a US patent for one of their cancer treatment technologies.

The treatment is called “fimaVACC” and is based on a type of light technology invented here in Norway at the Norwegian Radium Hospital.

The technology helps to transport cancer medicine more effectively to the targeted cancer cells. In this case, the technology enhances the effect of other cancer vaccines.

The US patent is for the use of fimaVACC together with cytokines, a small protein that is involved in cell signalling that regulates the immune responses.

The combination treatment has shown to be effective when enhancing the immune responses in cancer patients to fight off cancer.

Per Walday, CEO of PCI Biotech, said: “There are many vaccines under development utilising cytokines to elicit immune responses. The US patent granted today is important for PCI Biotech’s development strategy, as it supplements our ability to generate an internal future vaccine pipeline, in addition to bringing value for the fimaVACC technology in partnering efforts.”

View the entire press release from PCI Biotech

New results from clinical study

Our member BerGenBio, a Norwegian biopharmaceutical company, has given an update on one of their phase II clinical trials.

The phase II trial aims to determine the clinical efficacy of one of the drugs BerGenBio has developed, namely “bemcentinib”.

Bemcentinib is an AXL inhibitor, a novel type of cancer therapeutic agent.

BerGenBio can now show that the first stage clinical efficacy endpoint has been met.

The clinical trial is evaluating a combination treatment, consisting of bemcentinib and the immunotherapy drug Keytruda.

The patients who have been treated in this trial all have non-small cell lung cancer (NSCLC) and have previously failed checkpoint inhibitor therapy.

Richard Godfrey, Chief Executive Officer of BerGenBio, said: “Reversing resistance to immune checkpoint inhibitors in patients who have relapsed on immunotherapy is a highly desirable alternative to the second-line chemotherapy standard-of-care. We are very excited with these early results in this challenging setting and look forward to expanding the study to confirm these findings and reporting comprehensive translational insight.”

View the entire press release from BerGenBio

 

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Sune Justesen and Stephan Thorgrimsen from Immunitrack are pleased to receive the Eurostars funding to continue to develop the company's prediction tools. Photo: Immunitrack

New tool to improve cancer vaccines receives funding

Sune Justesen and Stephan Thorgrimsen from Immunitrack

Oslo Cancer Cluster member Immunitrack has been awarded a grant from Eurostars to develop their prediction tool for cancer vaccines.

Immunitrack is a biotech company that develops software, which predicts immune responses and assesses new cancer vaccines.

Developing a new vaccine can be a lengthy and expensive process, with a high risk of failure. One key to success is being able to predict how the patient’s immune system will react, so drug developers can bring forth therapies that mobilize the immune system to fight the disease. Immunitrack’s tools can help developers predict the impact of a new drug on the patient’s immune system, before entering clinical trials.

Eurostars supports international innovative projects and is co-funded by Eureka member countries and the European Union Horizon 2020 framework programme. The funding will be used by Immunitrack over a 24-month period for the ImmuScreen Project, to develop a new prediction tool. It will both improve how cancer vaccines work and how to track patients’ immune responses.

“This Eurostar project will give additional momentum to the ongoing development of a best in class neo-epitope prediction tool, PrDx TM, by Immunitrack,” says Sune Justesen, CSO at Immunitrack.

Immunitrack will receive a total of approximately €750 000 from Eurostars, together with the Centre for Cancer Immune Therapy (CCIT), based in Herley, Denmark. CCIT aims to bridge the gap between research discovery and clinical implementation of treatments in the field of cancer immunotherapy.

“The collaboration with the Danish Cancer Center for Immune Therapy, is certainly an important step in validating and implementing PrDx, in the immune therapy treatment of cancer patients,” says Sune Justesen, CSO at Immunitrack.

Immunitrack will handle the software development, while CCIT performs the in vitro validation. The clinical validation will be carried out in melanoma patients. The results will help to characterize immune responses and help to understand why some tumours are immune to novel cancer vaccines.

 

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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?

Nobel Laureate Dr James Allison and oncologist Dr Padmanee Sharma will become Strategic Advisors for our member, the Oslo-based biotech company Lytix Biopharma. Photo: Shutterstock

Nobel Prize winner joins Lytix Biopharma

Dr James Allison, Dr Padmanee Sharma

The Nobel Laureate Dr James Allison and oncologist Dr Padmanee Sharma will become strategic advisors for our member Lytix BioPharma.

Oslo Cancer Cluster’s member Lytix BioPharma announced this week that the cancer researchers and married couple Dr James Allison (PhD) and Dr Padmanee Sharma (MD) will join their Scientific Advisory Board.

Dr James Allison was, together with Dr Tasuku Honjo, awarded the 2018 Nobel Prize in Medicine last December. The renowned cancer researchers received the award for their ground-breaking work in immunology. It has become the basis for different immunotherapies, an area within cancer therapy that aims to activate the patient’s immune system to fight cancer.

Dr Sharma is a distinguished oncologist, who has focused her work on understanding different resistant mechanisms in the immune system. These resistant mechanisms sometimes hinder immunotherapies from working on every cancer tumour and every cancer patient.

Lytix Biopharma is a biotech company, located in the Oslo Cancer Cluster Incubator, that develops novel cancer immunotherapies. They are making an “oncolyctic peptide” – a drug with the potential to personalize every immunotherapy to fit each patient.

  • Please visit Lytix BioPharma’s official website for more information about their product

Edwin Clumper, CEO of Lytix BioPharma, expressed how thrilled he was to welcome Dr Allison and Dr Sharma:

“We are honoured that they have offered their support to further the development of our oncolytic peptides with the aim to tackle tumour heterogeneity – an unresolved challenge in cancer treatment.”

 

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Ultimovacs enters the Oslo Stock Exchange

Ultimovacs enters stock exchange

Oslo Cancer Cluster member Ultimovacs, a Norwegian cancer vaccine company, has raised NOK 370 million and entered the Oslo Stock Exchange on Monday 3 June 2019.

There was a stir of interest among both national and international investors when Ultimovacs announced they will enter the Oslo Stock Exchange. Several interested parties have now become shareholders in the company, totalling approximately 1 500 shareholders.

“It is good for the Norwegian health industry and for Ultimovacs when national and international investors show the company this kind of trust. In today’s uncertain market, it is especially nice with such a large interest, from both international investors and small savers. I look forward to following the company further,” says Jonas Einarsson, Chairman of the Board in Ultimovacs and Managing Director in Radforsk.

The funds that Ultimovacs has raised will go to financing the development of their universal cancer vaccine, UV1. A large clinical study will document the effect of the vaccine. UV1 will be combined with other immunotherapies in patients with malignant melanoma (a type of skin cancer) at around 30 hospitals in Norway, Europe, USA and Australia.

Ultimovacs has already run two successful clinical trials of the vaccine on patients with lung cancer, prostate cancer and malignant melanoma.

“The cancer vaccine has shown promise in the studies we have conducted at the Norwegian Radium Hospital. Based on the results, we have established a development programme to document that our vaccine has effect on cancer patients. I am very happy that we now have entered the Oslo Stock Exchange. It means that the practical conditions are in place to put our development programme into action,” said Øyvind Kongstun Arnesen, Chief Executive Officer in Ultimovacs.

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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

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.

 

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: 

 

Encouraging news from BerGenBio

A second group of patients have been added to an ongoing phase II clinical study of a drug combination to treat lung cancer.

 

The ongoing trial is a collaborative effort between two members of Oslo Cancer Cluster: Norwegian biopharmaceutical company BerGenBio and US-based pharmaceutical company Merck (known as MSD in Europe). It involves an kinase inhibitor called bemcentinib, developed by BerGenBio, in combination with an immunotherapy drug called Keytruda (also known as pembrolizumab) from MSD.

 

“Throughout 2018, we reported encouraging updates from our ongoing proof-of-concept phase II clinical trial assessing bemcentinib in combination with Keytruda in advanced lung cancer patients post chemotherapy.”
Richard Godfrey, Chief Executive Officer, BerGenBio

 

The second group will involve patients that have been treated with immunotherapy before, but that have experienced a progression of the disease. There are various treatments available for patients with non-small cell lung cancer, but patients often acquire resistance to treatment. New treatments that can overcome these resistance mechanisms are therefore urgently needed.

 

“I am pleased that we are now extending the ongoing trial to test our hypothesis also in patients showing disease progression on checkpoint inhibitors.”
Richard Godfrey, Chief Executive Officer, BerGenBio

 

The aim is to evaluate the anti-tumour activity of this new drug combination. Preliminary results from the second patient group of the study are expected later this year. BerGenBio is in parallel also developing diagnostic tools to see which patients are most likely to benefit from their drug.

 

The decision to extend the trial was based on new positive results from pre-clinical studies, which were presented at the American Association of Cancer Research (AACR) earlier this week. The results open for the possibility to use bemcentinib both as a monotherapy and in combination with other cancer treatments on a broad spectrum of cancers.

 

 

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