31 March 2025
Biological processes determine viro-immunotherapy effectiveness
"One of the four viruses always has an effect."
An oncolytic virus can work well for one patient yet have little effect for another. Why is that? Eftychia Stavrakaki will shortly defend her doctoral research into the effects and effectiveness of four different viruses in treating brain tumours. Drawing on her background in biology and immunology, she developed a model that maps specific biological processes in relation to the immune response. Her research offers important insights into the use of tumour-killing viruses, not only for brain tumours but also for other aggressive cancers such as pancreatic cancer.
Strati-Vir project
Eftychia Stavrakaki’s work is part of Strati-Vir, a large collaborative study by Erasmus MC and Leiden University Medical Centre initiated by Martine Lamfers, Gabri van der Pluijm and Bernadette van den Hoogen. Support Casper renewed its funding for the project this year. The researchers aim to create a toolbox of effective oncolytic viruses by examining both how each virus affects a particular type of tumour cell and the individual characteristics of each patient. The project takes its name from this stratification of viruses and patients.
Eftychia explains: "After completing my bachelor’s degree in molecular biology at the University of Crete, I moved to the Netherlands in 2016 to study biomedical sciences in Utrecht. I then joined Erasmus MC in Rotterdam for my PhD research. I had already worked extensively with herpesvirus in Crete, and encountered it again here as one of the four oncolytic viruses. We grow small pieces of tumour tissue outside the body so that we can expose them to the viruses. We also use patients’ blood to examine the effects on immune cells. It is a complex picture: tumours vary greatly in their genetic make-up, and people’s immune systems are equally diverse."
Encouraging progress
As with pancreatic cancer, the outlook for people with brain tumours is often poor and treatment options are limited. Oncolytic viro-immunotherapy may offer a new approach. Eftychia says: "Glioblastoma is both the most common and the most aggressive type of brain tumour, and it has been the focus of my research. Oncolytic viruses have produced impressive results, but only in a limited number of patients. We therefore began investigating which factors influence a virus’s effectiveness. We use four of the most common oncolytic virus strains: herpesvirus, adenovirus, reovirus and Newcastle disease virus, which causes a mild form of avian influenza."
"The immune system is crucial in virotherapy. As well as killing tumour cells, we want the virus to stimulate the patient’s natural defences to attack the cancer. We have found that a virus’s ability to kill tumour cells is not necessarily linked to how strongly it activates the immune system. We also know that particular cellular processes affect tumour-cell killing, which helps explain why a virus works for one patient but not another. Mapping these processes enables us to predict more accurately how someone may respond. Among the four viruses we studied, at least one was effective in each case."
Toolbox for success
The study’s insights into oncolytic viruses in glioblastoma may also help researchers develop effective treatments for pancreatic cancer. As the Strati-Vir toolbox develops, it becomes better at predicting which virus is most likely to work. Eftychia says: "In principle, the knowledge gained from brain cancer research can also be applied to pancreatic cancer. We want to predict a person’s response at both immune-cell and tumour level so that treatment can be personalised and made more effective. Put simply, the aim is to use the virus best suited to that patient to kill tumour cells and activate the immune system. There is still much to discover, which is why the research continues. Immunotherapy is a fascinating field in which important advances follow one another rapidly. That is exciting for me as a researcher and highly relevant to everyone affected by an aggressive cancer. Matching each patient with the most suitable virus can improve the chances of viro-immunotherapy succeeding."