Professor Ron Fouchier
Professor Ron Fouchier is a molecular biologist and Professor of Molecular Virology in Erasmus MC’s Viroscience department. He studies viruses at molecular level. "Once we understand the small number of molecules that control a virus, we can engineer it and use it for a particular purpose rather than simply accepting its natural behaviour," he explains.
Fouchier has been part of OVIT since its foundation. Professor Casper van Eijck approached him for his expertise in Newcastle disease virus (NDV), prompting a programme to make the virus both safer and more effective.
Viruses are tiny packages of genetic material that reproduce inside cells. Their diversity is greater than that of plants, animals and fungi combined, yet people mainly know the small minority that cause disease. Engineering has already turned viruses—including modified forms derived from HIV—into useful medical tools. Fouchier notes that technology originating in HIV research can now treat children with otherwise fatal genetic disorders.
The same principle can be applied to cancer. Natural viral infections have occasionally caused tumours to regress, and researchers have investigated viruses such as measles virus, herpesvirus and NDV as treatments. Weakened vaccine viruses offer a safe starting point, but effective cancer therapy may require carefully engineered viruses with stronger antitumour activity.
NDV can be harmful to poultry but generally causes no illness in people. The team modifies its genes so that it attacks cancer cells yet cannot reproduce in birds if it reaches the environment. They also add genes intended to stimulate the patient’s immune system to recognise and destroy tumour cells.
Checkpoint inhibitors have transformed treatment for several cancers, but they are expensive and have had limited success in pancreatic cancer. OVIT researchers believe oncolytic viruses could generate a powerful immune response more efficiently by infecting a tumour and drawing the immune system’s attention to it. An engineered herpesvirus is already approved for melanoma; this project applies the principle to NDV and pancreatic cancer.
After comparing several viruses in different cancer cells, the researchers selected NDV for its tumour-killing ability. Engineering may improve that effect further. Treatment is expected to cause temporary flu-like symptoms as the immune system responds; that same response is intended to help clear the tumour.
Strict rules protect patients and the environment whenever a virus is administered. Fouchier and Professor Rob Hoeben have advised Dutch and European gene-therapy studies on environmental risk for many years. Their teams work with regulators and other specialists to develop and apply evidence-based safety criteria.
Gene therapies have historically taken twenty to thirty years to develop. To bring these viruses to patients sooner, the team runs engineering, manufacturing, effectiveness testing and safety assessment in parallel. A candidate must work in tumour cells in the laboratory, show efficacy and safety in an animal model, and pose no unacceptable environmental risk before safety and effectiveness can be studied in patients.
Dutch authorities coordinate two rigorous regulatory routes: the Central Committee on Research Involving Human Subjects assesses patient safety, while the Office for Genetically Modified Organisms considers environmental risk. Completing these national and European requirements alongside the scientific work could allow a first patient study within several years.
The findings may also benefit other hard-to-treat cancers, including glioblastoma and prostate cancer, as well as future gene-therapy research.