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Our own immune system as a weapon against cancer
Research

Our own immune system as a weapon against cancer

Researchers from KU Leuven and UZ Leuven are playing an important role in research into using immunotherapy as a cancer treatment.

8 minutes
08 June 2020

Researchers from KU Leuven and UZ Leuven are playing an important role in international research into using immunotherapy as a cancer treatment. They’re looking for ways to employ the immune system in the fight against cancer, for example by using gene technology. Additionally, they’re working to determine the optimal use of medicines that affect the functioning of the immune system.

We’re currently achieving fantastic results. However, fundamental research into immunotherapy is more necessary than ever.

One of those researchers is Professor Sabine Tejpar. She’s researching immunotherapy in the treatment of colon cancer. ‘We’re currently achieving fantastic results. However, fundamental research into immunotherapy is more necessary than ever. We don’t yet know the principles and mechanisms that form the basis of an effective immunotherapy. However, with the necessary manpower and resources, the whole picture will undoubtedly become clear in the long term.’ Financing from various sources, including Opening The Future, is being used to help make this possible.

‘Our immune system is the strongest weapon our body has to defend itself against invaders. Unfortunately, it usually fails to destroy malignant cells,’ says Professor Michel Delforge, chairman of the Leuven Cancer Institute (LKI). ‘It’s very rare for an incipient cancer to be shut down by the immune system. A well-functioning immune system cannot therefore prevent someone from developing cancer.’

‘Our immune system is the strongest weapon our body has to defend itself against invaders. Unfortunately, it usually fails to destroy malignant cells,’ says Professor Michel Delforge, chairman of the Leuven Cancer Institute (LKI). ‘It’s very rare for an incipient cancer to be shut down by the immune system. A well-functioning immune system cannot therefore prevent someone from developing cancer.’

Additional immune cells

The best known form of immunotherapy is stem cell transplantation to treat malignant diseases of the blood and bone marrow. After a round of cancer treatment, the patient's immune system is destroyed. Then the immune system of a healthy donor is introduced through the transplantation of stem cells, a process that then produces immune cells in the patient's body. The idea is that the donor's immune cells will shrink the remaining cancer and prevent the cancer from returning.

Stem cell transplantation has been used for decades, but unfortunately it still carries considerable risks should rejection symptoms occur.

This therapy has been used for decades, but unfortunately it still carries considerable risks should rejection symptoms occur. In addition, the donor's immune cells can also attack healthy tissues, such as the skin, liver or the gastrointestinal tract. This therapy is therefore limited to a number of specific syndromes, such as acute leukaemia.

Proteins as bait

Another form of immunotherapy that researchers at LKI have been studying for some time is vaccination. The inspiration for this was taken from vaccination against infectious diseases. The flu vaccine is a good example; you inject a patient with certain proteins from the flu virus, which activates the immune system. In a similar way, you can try to elicit an immune response using certain proteins that are unique to cancer cells, and that response then eliminates the remaining cancer cells. Promising results are being achieved with certain cancers, but we’re still waiting for a major breakthrough.

Monoclonal antibodies2

Genetically tailored technology

There’s an even more promising future in drug immunotherapy. Antibodies can now be made in a biotech lab based on gene technology. Modern antibodies are made entirely from human sources, so that these 'artificial' antibodies are not themselves destroyed by the immune system. They’re referred to as monoclonal antibodies and are always directed against one specific antigen. Such an antigen is a substance, usually a protein, that often appears on cancer cells. Monoclonal antibodies bind to the antigens, including the cancer cell, by cleaving to them like a magnet. Sometimes their action is more indirect, such as by activating the immune system to destroy cancer cells.

Modern antibodies are made entirely from human sources, so that these 'artificial' antibodies are not themselves destroyed by the immune system.

We currently have a large store of monoclonal antibodies that have been used for years in the fight against both very frequent and more rare cancers. Increasingly, a dose of chemotherapy or radiotherapy is also attached to such an antibody. The antibody then becomes a transport vehicle to deliver chemotherapy or radiotherapy directly to the cancer cell. Another possibility is to stick two antibodies together (bi-specific antibodies), where one side binds with the cancer cell and the other side binds with the immune cell. In this way, the cancer cell and the immune cell are brought into contact with each other and the immune cell can more easily attack the cancer cell.

LKI Delforge 4 web

Plug in the socket

There’s yet another type of drug immunotherapy, the so-called checkpoint inhibitors. Their mode of action is somewhat more complex. Cancer cells often have receptors on their surface – again, proteins – that slow down immune cells and protect the cancer cell from being quickly destroyed. This works as follows: when cancer cells and immune cells meet, connections are made, much like when you plug a plug into a socket. A cancer cell can send a negative signal through that receptor that inhibits the immune cell. Checkpoint inhibitors act to switch off that negative signal so that the immune cell can better react against the cancer cell. Checkpoint inhibitors are already being used to treat different types of cancer: kidney cancer, skin cancer, lung cancer, and more.

Extra boost

Finally, there’s a third type of drug immunotherapy, the immunomodulators. These are medicines that can affect the immune system so that it’s better able to detect and destroy cancer cells. Research on these medicines is currently underway at LKI.

Immuuntherapie

CAR-T therapy

Professor Johan Van Eldere is chairperson of the international EUCCAT network that unites nine academic centres and focuses, among other things, on the development of CAR-T therapy.

This type of cancer therapy involves genetically altering the patient's immune cells, also called T-cells, by modifying their DNA so that the immune cells are outfitted with a protein on their surface, a receptor or CAR, that allows them to recognise cancer cells. This CAR-T treatment was a major breakthrough, but for the most part is still only used in haematology, and then only for a very limited subset of patients.

From acute to chronic

‘The availability of many different types of immunotherapy has expanded the arsenal of treatment options for many cancers,’ says Professor Delforge. ‘These new methods can also be combined with more traditional anti-cancer treatments. Immunotherapy is an indispensable part of treating cancer today and has contributed to a significant improvement in life expectancy in a large number of patients. Partly because of this, cancer is evolving from an acute life-threatening condition to a more chronic disease.’

Partly because of immunotherapy, cancer is evolving from an acute life-threatening condition to a more chronic disease.

There is only one ...

Nevertheless, Professor Delforge has a few reservations. ‘Apart from the fact that immunotherapy isn’t successful with all types of cancer, and therefore doesn’t always lead to a cure, you also have to take into account unwanted side effects. For example, complications sometimes arise when administering checkpoint inhibitors. Acting on the immune system can’t always go unpunished. CAR-T therapy can also have side effects; the results are spectacular, but there can also be a very strong inflammatory reaction in the body.’

LKI Delforge 8 web

Rational commitment

And then there is the financial aspect. The cost of immunotherapy treatment can easily reach more than € 100,000 per year per patient, says Professor Delforge. The therapy is often given for months or years. As a result, the budget for oncological medicines has increased by hundreds of millions of euros in recent years. This presents us with an enormous challenge, especially in times of crisis and economic recession.

Without thorough adjustments, such treatments will not remain affordable in the long term, according to Professor Delforge. ‘If we want to be able to continue offering immunotherapy to as many patients as possible in the future, we will have to use it as rationally as possible. The goal should be to use immunotherapy in the most intelligent manner to deliver the maximum effect.’

Predictive factors

‘To do this, we will have to make as much use as possible of predictive tests that can help to estimate in advance whether or not a particular therapy might work for a particular patient. Several research projects are currently underway within the LKI that focus on better identifying those factors that can help predict the effects, or possible side effects, of immunotherapy.

Several research projects are currently underway focus on better identifying those factors that can help predict the effects of immunotherapy.

’In addition, research is also being conducted within LKI to provide insight into the optimal duration of treatment with immunotherapy. That can also help to save on costs.’

The Leuven Cancer Institute (LKI) brings together all activities in the field of cancer medicine and cancer research within UZ Leuven and KU Leuven. The LKI unites scientists, clinical researchers, doctors and nurses who want to bring their knowledge and experience to bear in the fight against cancer. Research, therapy, and care all work together to lend strength to one another.