High-grade pediatric brain tumors are a big challenge in treating children's cancer. Despite years of research and different treatments, these tumors are still hard to treat. Tumors like diffuse midline gliomas, atypical teratoid/rhabdoid tumors, and relapse ependymomas don't have many treatment options and usually have poor outcomes. Even with surgery, chemotherapy, and radiotherapy, many children with these tumors have a low chance of survival. Because of this, there's an urgent need for new treatments that work better and have fewer side effects. Research into oncolytic viruses gives hope that they could be part of a bigger solution to tackle this problem.
What are oncolytic viruses?
Oncolytic viruses are viruses made to fight cancer. They enter cancer cells and use these cells to create more viruses. When the cancer cells are full of these new viruses, they burst open and die. This action also triggers the immune system to attack any remaining cancer cells.
Konstantinos Vazaios, the first author of the study, says: ‘In the past, oncolytic viruses weren't seen as a possible treatment due to concerns about their safety and effectiveness. But our findings suggest they could work. We still need to proceed with caution and conduct more tests, both in the lab and through clinical studies, to confirm their potential.’
About this study
Vazaios is a PhD student in the research group of Dr. Esther Hulleman. He is also supervised by Dr. Jasper van der Lugt and Dr. Friso Calkoen (both pediatric oncologists at the Máxima Center), and Dr. Martina Lamfers from Erasmus MC. ‘Lamfers and her team have collected a variety of oncolytic viruses over the years, which they use in research against adult glioma,’ says Vazaios. ‘They guided us through the specialized techniques required to handle these viruses properly, and brought them to the Máxima for investigation in pediatric brain tumors.’
The goal of their study was to build on previous experiments to see if these viruses could successfully eliminate pediatric brain tumor cells. Vazaios shares: ‘Our lab results look promising. They indicate that these viruses can eliminate certain cancers more effectively than others, particularly based on their genetic profiles.’ This research highlights how genetics could play a crucial role in determining the best treatments.
Their findings were published in Molecular Therapy Oncology.
Advancing oncolytic virus treatments
A few years ago, research on oncolytic viruses looked very promising and garnered much media attention, but many initial studies did not fully meet expectations. Currently, one oncolytic virus therapy has been approved by the FDA for melanomas, and several others are completing Phase III trials, showing progress in the field. Vazaios explains: ‘New treatments usually start with high hopes, but sometimes they don't work clinically as well as in the lab because the results can vary between different patients. It's crucial to keep researching to understand why and make improvements.’
In this study, Vazaios and his colleagues investigated how different cancers respond to various viruses. ‘Our results show that not all viruses work on all tumors. Some tumors have specific traits that make them more or less likely to respond to certain viruses. Also, some viruses can work too quickly or too slowly, depending on the type of tumor,’ he says.
Dr. Jasper van der Lugt, who started this study, adds: ‘Instead of using the same treatment for every child with brain cancer, we are working together with Erasmus MC to create virus treatments tailored to each tumor's unique genetic makeup. This approach will help us choose the best virus treatment right from the start, like during a biopsy, making treatments more precise and effective.’
Combining oncolytic viruses and immune therapy
Vazaois aims to continue this research by combining oncolytic viruses with immune therapy. ‘The viruses activate the immune system through the erupting cancer cells. Hence, we can target the cancer more accurately with another treatment called CAR T-cell therapy,' he says.
Right now, they are testing this idea in the lab and hope to see good results by the end of the year. ‘It's still early to say for sure, but I believe using both treatments together could work better for treating children with cancer.’
From lab to clinic
Van der Lugt concludes by discussing potential clinical applications. ‘Our research shows promising laboratory results, but the journey toward clinical application is just beginning,’ he explains. He highlights a recent study in the New England Journal of Medicine that underscores the need for further research.
‘We need more studies to validate these findings across different patient groups and confirm the results in a broader human population,’ he adds. ‘This upcoming study could also help us determine if RNA-sequencing can predict patient responses to treatments, enhancing our understanding of which therapies are most effective for specific cases. Currently, we are planning a new study to expand this research. It aims to build a stronger foundation for clinical applications. This could lead to treatments that target remaining cancer cells more effectively after surgery, potentially speeding up recovery for children with cancer.’
Funding
The research team is grateful for the support received from various sources, which is vital for advancing their studies. Among contributors are Inspire2live, Choir4hope, Stichting Kinderen Kankervrij (KiKa), Foundation Support Casper and Familie van der Velden.