Dr Jeroen de Vrij
Imagine tiny particles travelling through the body like delivery vehicles carrying medicine. It may sound futuristic, but Jeroen de Vrij’s research into exosomes could bring this approach closer to clinical use. He explains: "Exosomes are extremely small and can travel through the body effectively. That made me wonder whether we could place oncolytic viruses inside them and use the exosomes to carry those viruses deep into hard-to-reach tumours. I am investigating how we can harness adenovirus against cancer by enclosing it in an exosome."
Exosomes were once thought to serve merely as waste containers through which cells discarded excess proteins. We now know that they perform far more important functions, including communication between cells. Jeroen says: "I began researching exosomes in 2010, when the field was still entirely new. We gradually discovered that the body contains vast numbers of these tiny particles and that they have many important roles. They help cells communicate, contribute to cell growth and can enter and alter other cells. From 2014, I focused increasingly on using exosomes to treat glioblastoma, an aggressive brain tumour with limited treatment options and a poor prognosis. This allowed me to combine that work with another passion: oncolytic viruses, particularly adenovirus. As a biotechnologist, I enjoy designing and building new biological tools. By combining exosomes with oncolytic adenovirus, I created what we call adenosomes. An initial small-scale study showed that these adenosomes can penetrate deep into the brains of mouse models and attack tumour cells. Our current research examines several exosome-based therapies for brain tumours as well as their potential in pancreatic cancer."
Clean from the inside
Both glioblastoma and pancreatic cancer can suppress the immune response. Jeroen explains: "A tumour can hide itself, preventing the body from recognising and clearing the harmful cells. Adenosomes can penetrate the tumour and expose cancer cells to the patient’s immune system, prompting it to attack. At the same time, the adenosomes can destroy cancer cells from within. Exosomes are so small that about 10,000 can fit inside a single cell, and they can pass through the dense layers of connective tissue found in glioblastoma and pancreatic cancer. We hope to demonstrate a therapeutic effect that exceeds that of current chemotherapy. We are studying different variants and forms of exosome therapy so that each patient might receive the most suitable option. Exosome treatment may also cause far fewer side effects than chemotherapy. Although much remains uncertain at this stage—we began at the end of last year and expect to need another year before drawing firm conclusions—we are hopeful that this could represent an important advance for hard-to-treat cancers."
Different levels at the same time
The study is not yet halfway through, but Jeroen is already preparing for the next phase: "Producing exosomes is particularly complex, and because they are so small we need very large quantities to treat patients. Working with viruses also involves carefully managed risks and strict safety requirements. We are therefore developing production techniques now, so that exosomes can eventually be used in cancer treatment. We work on several stages at once to bring any successful treatment to patients as quickly as possible. If everything proceeds as planned, the first adenosomes could be administered to people in four years. The final six months of the current research phase will involve experiments in mouse models, which we hope will demonstrate a meaningful therapeutic effect. It is also rewarding to be part of the Oncolytic Viro-Immunotherapy programme. Researchers once worked largely in isolation; now we collaborate. That is both stimulating and educational, and it helps us make faster progress towards effective treatments for cancers such as glioblastoma and pancreatic cancer. I hope that people receiving either diagnosis will one day have a far better prognosis."