Dutch research is among the best in the world. That is why KIJK editor Laurien Onderwater introduces you to a Dutch scientist every month in this column. This time: Arjan Griffioen is working on a vaccine against cancer.
Arjan Griffin
Cancer is still the most common cause of death in the Netherlands. In 2022, more than 170,000 people died in our country, 28 percent of them from the consequences of this disease. Scientists are working hard on new ways to get that percentage down. The disadvantage of existing treatments such as chemotherapy is that they have many side effects. Arjan Griffioen, professor of experimental oncology and angiogenesis (blood vessel formation) at Amsterdam UMC, is therefore taking a different tack: he is developing a therapeutic cancer vaccine.
Griffioen, who graduated in medical biology at VU University Amsterdam with a specialization in immunology, obtained his PhD on bacterial infectious diseases in children. Very interesting, he says, but the field did not belong to the mainstream research areas. “I had sent several publications to various scientific journals. There I was told that the research was excellently conducted and that the articles were well written. Yet my articles were rejected, because: not a priority. At the time I thought: I am not going to work very hard so that someone else can then say that my research is unimportant.”
That is why Griffioen decided to switch to a research area that was mainstream after his PhD: oncology. Pretty crude, he admits. “Bacterial infections kill maybe ten children a year. Many more people die from the consequences of cancer, which is why that research is seen as more important.”
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Gatekeepers
In the late 1990s, Griffioen focused on research into the role of the immune system in combating tumours. He investigated how he could fight tumors with the help of immune cells (white blood cells that protect the body against intruders).
Immune cells do not just end up in tumors: they are in our bloodstream and must therefore first pass through the wall of the blood vessels, a hermetically sealed barrier. Blood vessels contain so-called adhesion molecules, which act as gatekeepers. If an immune cell binds to it, the adhesion molecule guides it out to its destination. Yet immune cells often fail to invade a tumour.
In 1996, Griffioen discovered why: “In order to multiply, tumor cells form new blood vessels – a process called angiogenesis – that supply them with nutrients. But there are no adhesion molecules in those blood vessels, which means that immune cells cannot bind to them in order to penetrate the tumour. That was the most important discovery of my life, because now we knew what to do to make tumors sensitive to immune cells.”
Incidentally, not only tumors pull this trick; they ‘cheated’ him. “An embryo consists of 50 percent DNA from the mother and 50 percent DNA from the father. This makes it semi-foreign. In a developing embryo, the blood vessels grow with it and to ensure that the mother’s immune system does not attack the child, the adhesion molecules are also absent there.”
Benno
Griffioen’s goal is to find out how to use this mechanism against tumors. For example, he has done a lot of research into angiogenesis inhibitors (drugs that prevent blood vessel formation in tumours) and in particular how they can enhance immunotherapy in cancer patients. In immunotherapy, a patient receives medicines that ensure that the immune system recognizes, clears and destroys the cancer cells as foreign. “But as long as tumor cells can protect themselves against these immune cells, because their blood vessels do not contain adhesion molecules, that is of little use. With medication that counteracts angiogenesis in tumors, immune cells can launch the attack.” To date, eight such combination treatments have already been approved by the US Food and Drug Administration.
Still, the professor is not satisfied, because these angiogenesis inhibitors also cause side effects in humans, such as blood clots. He therefore looked at proteins that are present on tumor blood vessels but not in healthy tissue, and found fifteen. He wants to target vaccines against these proteins so that immune cells attack them and thus destroy the tumour. Such a therapeutic vaccine would make angiogenesis inhibitors superfluous. “Moreover, it is very cheap to make and has zero side effects, because it only works on the tumor.”
The first results in dogs are promising. Griffioen worked with veterinarians who had dogs with cancer in their practice and saw that in all forty treated dogs the tumor became smaller or disappeared completely. “Our most famous example is Benno the Bernese Mountain Dog. He had a large tumor in his bladder and a poor prognosis. We were allowed to vaccinate him with our experimental vaccine and two weeks later the tumor was already showing holes.” That was three years ago. Benno is now still cancer-free and is twelve years old.
But a dog is not a human being, and although the DNA of both species is largely similar, it is precisely the differences that make it difficult to translate the results. Nevertheless, Griffioen’s groundbreaking research gives people hope. This also became apparent the day after the scientist had talked about the study in Sophie Hilbrand’s talk show; his mailbox was filling up and the phone was ringing. A human study has now started, but it will be several years before the vaccine is available.
This Onderwater Ondervraagt is also featured in the extra thick summer issue of KIJK, which can be ordered via the button below.
Beeld: iStock/Getty Images
2023-07-29 07:00:18
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