Viruses awaken the immune system of children with brain tumours
Thanks to the latest developments, as reported in the journal Frontiers in Immunology(opens in new window), oncolytic viruses are emerging as a powerful new tool in the fight against cancer. These viruses are engineered to infect and kill tumour cells, while stimulating the body’s immune system to recognise and attack the cancer. Once inside a tumour cell, the virus replicates and causes it to burst, releasing viral particles and inflammatory signals that help recruit immune cells into the tumour environment. This dual mechanism has gained growing interest in adult cancers, but its use in paediatric brain tumours has until now remained largely unexplored due to safety and delivery concerns.
Engineered virus against paediatric brain tumours
The ViroPedTher(opens in new window) project, funded by the European Research Council (ERC), set out to evaluate whether oncolytic viruses can be used safely and effectively in paediatric patients, and to understand how they interact with the unique immune environment found in these tumours. At the heart of the therapy is Delta-24-RGD(opens in new window), a modified adenovirus engineered to selectively infect and replicate in tumour cells that have defects in a common cancer pathway known as the retinoblastoma protein(opens in new window). The virus also includes a special modification, called the RGD motif, which helps the virus enter tumour cells more efficiently by binding to certain surface proteins often overexpressed in aggressive cancers.
From bench to bedside
Delta-24-RGD has shown promise in adult gliomas, but ViroPedTher is the first initiative to study its use in children, especially through direct injection into the tumour. The virus was administered in 12 children with high-risk brain cancers. Results from the Phase I trial, published in the New England Journal of Medicine(opens in new window), showed that the therapy was well-tolerated even in the pons, a critical and sensitive area of the brainstem. Most importantly, median overall survival reached 17.8 months, compared to the standard of 12-14 months, and two children lived over five years after treatment, one of whom remains alive nearly six years later.
Waking up the immune system against paediatric tumours
One of the challenges in paediatric brain tumours is that many have an immune-silent or ‘cold’ microenvironment. These tumours are often filled with myeloid cells such as microglia and macrophages but lack the T cells that usually kill cancer. ViroPedTher found that Delta-24-RGD helped to change this. “The virus reprogrammed the tumour’s immune environment; it activated the myeloid cells and attracted lymphocytes into the tumour, sparking a much stronger immune response,” explains project coordinator Marta Alonso(opens in new window) of Cima University of Navarra. This immune awakening is critical. By shifting the tumour from immunosuppressive to inflammatory, Delta-24-RGD helps the body recognise and sustain its attack on cancer, even after the virus is gone.
Future treatment offers precision and hope
ViroPedTher has demonstrated that oncolytic virotherapy, long studied in adult cancers, can be safely adapted for paediatric brain tumours. By using Delta-24-RGD to destroy tumour cells and reshape the immune landscape, the project has opened the door to a new kind of treatment that offers both precision and hope. With the first trial complete, the ViroPedTher team is now working on a next generation of oncolytic viruses. These new candidates are being designed to better match the biological traits of some of the most challenging childhood cancers.
