Dr. Martine Lamfers
Dr Martine Lamfers heads the Neurosurgery laboratory within the Erasmus MC Brain Tumour Centre. She has more than fifteen years’ experience researching viruses as treatments for brain tumours, including the use of adenovirus, which normally causes common respiratory infections.
Brain tumours and pancreatic cancer are both highly aggressive diseases for which effective treatments remain limited. Survival has improved very little over the past forty to fifty years, making new approaches urgently necessary.
One such approach uses oncolytic viruses. Some immune cells activate an immune response, while suppressor cells restrain it. Suppressor cells in and around a tumour can prevent the immune system from recognising and clearing the cancer. Oncolytic viruses may sound an alarm within this immune-suppressive environment, prompting the immune system to identify and attack tumour cells. The approach may also be combined with other forms of immunotherapy.
Dr Lamfers has studied oncolytic viruses since the OVIT consortium was established. Erasmus MC’s Neurosurgery department has extensive experience in this field, and she has contributed to a clinical trial of an oncolytic adenovirus for brain tumours. That expertise can help bring similar treatments into pancreatic cancer trials. Before this can happen, researchers must improve the viruses’ safety, demonstrate their safety and effectiveness in several model systems, and establish large-scale production under rigorous quality controls. Meeting all legal and regulatory requirements is another major part of the process.
A US study found that some patients responded very well to oncolytic virus therapy while others did not respond at all. Laboratory work similarly shows that tumours differ in their sensitivity: a tumour resistant to one virus may be highly sensitive to another. Because infection is the first step in the chain of events that activates the immune system, selecting the right virus for each tumour is essential. This personalised virotherapy could increase the proportion of patients who respond.
Researchers are testing four oncolytic viruses on cultured brain-tumour tissue from dozens of patients who underwent surgery at Erasmus MC. Sensitivity varies greatly. By comparing each tumour’s genetic information with its response to the four viruses, the team aims to identify profiles that predict which virus will work best for a particular patient. Once identified, these profiles will be validated. Erasmus MC is developing pancreatic cancer models in parallel so that predictive profiles can also be tested for this disease. The aim is to improve the effectiveness of oncolytic virus treatment for both tumour types.
Bringing even one oncolytic virus into clinical practice is a considerable challenge. Within a few years, however, I hope we will have at least three viruses ready for trials, allowing us to choose the most suitable one for each patient. We hope these viruses, perhaps combined with other therapies, will improve survival. The entire OVIT consortium contributes its expertise to solving this puzzle. Together, we can make substantial progress in the years ahead. This form of collaboration is unique in the Netherlands. — Dr Martine Lamfers.