Immunotherapy: Finding the Right Fit

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

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

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

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

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

You can read about it here!

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

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

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

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

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

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

How Cancer Research Becomes a Company

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

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

How Our Genes Will Change Cancer

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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