Collaborating on behalf of cancer patients

‘The NKI is very science-driven, so that's a value we share,’ says Juliëtte van den Noort, Experienced Clinical Scientist in the Immunology group. ‘Now, we build on that common ground in a collaborative project on infusion reactions, which are adverse effects of intravenous drug administration, such as skin rashes or a drop in blood pressure’. Her colleague Igor Radanović adds: ‘We now hope to contribute to patient care at the NKI-AVL, in predicting and possibly preventing infusion reactions. In the longer term, we hope we can also jointly research new treatments in oncology.'

Van den Noort has been researching infusion reactions for some time, looking in particular at the role of the complement system. Infusion reactions can also be triggered by cytokines. ‘In our healthy volunteers, infusion reactions are very rare, happening just a few times every year’ says Van Noort. ‘Which is fortunate, because they are a burden to our participants, but it also means it’s quite a challenge to collect enough material to investigate infusion reactions.’

In cancer patients who receive chemotherapy and other treatments, infusion reactions are much more common. It is a problem that causes additional discomfort in patients who are already vulnerable and who undergo stressful treatments. That’s why it emerged as a valuable topic for collaboration between Dr Matthijs Moerland, director of the research laboratory and immunology and Marloes van Dongen, an oncologist at the NKI who obtained her PhD in 2015 on research she had done at CHDR.

‘I now go to the NKI-AVL regularly to collect blood samples from patients with breast cancer who receive paclitaxel or other chemotherapy,’ Radanović says. 'We keep track of who gets an infusion reaction and who doesn't and exactly which symptoms occur. That offers opportunities to look at the role of various factors in the mechanism underlying these reactions. Hopefully this will lead to better ways to predict and prevent infusion reactions.' Already, oncology patients are being pre-treated with an antihistamine or dexamethasone to prevent an infusion reaction. Van den Noort: ‘We want to study the blood of patients see if this premedication inhibits complement activation. And we will use an ex vivo challenge with the chemotherapy to see if the drug is able to trigger complement activation in blood.'

In the future, CHDR’s expertise in immunology may lead to other collaborations with NKI. Radanović cites the immunological challenge models that CHDR is currently working with, such as the LPS challenge and vaccination with the KLH neoantigen: 'In the future, we want to use those immunological challenge models to study the effects of new oncological Immunotherapeutics in healthy volunteers. We could also use some of them to study the immune system of cancer patients.' Van den Noort: ‘In spite of the popularity of immunotherapeutic agents, there is still much unknown about the way the immune system operates in patients with cancer. We know that many tumours suppress the immune system and that treatments such as chemotherapy and radiotherapy affect the immune system. But as far as I’m aware, there have not been many studies using functional tests such as our challenge models. So here too, by working together, we could gather knowledge that is valuable to both NKI-AVL and CHDR, and of course to cancer patients.'