Funded by the Dick Vitale Pediatric Cancer Research Fund
When the body is unable to fix damaged DNA, it can cause some childhood cancers to grow very quickly. These cancers have many DNA changes (called “mutations”) so we call them “hypermutant”. Some children are born with a syndrome, called CMMRD, which makes them develop a lot of these hypermutant cancers at a young age. A treatment called immunotherapy has shown positive results in these patients. However, it doesn’t work for everybody and when a cancer is found late, about 40% of children will get worse, even after treatment. Immunotherapy can also cause side effects, some of which are serious. Recently, we discovered that mRNA-LNP vaccines (similar to those used for COVID-19) may actually be able to prevent cancers in children with CMMRD. These vaccines have very few side effects and might help many patients. However, we still need to learn more about what components make an effective vaccine and then test it in human and animal models. In this project, we will do three things. We will first determine what should be included in a vaccine to make it work well. We will then test the vaccine in mice to see if it can prevent cancer. Finally, we will see how well the vaccine works and how safe it is for humans. To do this, we will work with international collaborators who have experience making vaccines. This work has the potential to help children with many other cancer-causing syndromes, as well as common adult cancers.
