Identify the ideal vaccine targets

People with Lynch syndrome are much more likely to get cancer than those without it. This is because they are born with an alteration in one of a series of genes that makes it difficult for their bodies to repair DNA correctly. As a result, their cells accumulate abnormal changes in DNA (mutations) over time, which can cause cancer.

These mutations are not random; they appear in patterns, and some are shared across many people with Lynch Syndrome. They often lead to abnormal proteins appearing on the cell surface and can be recognised by the immune system. Vaccination aims to train the immune system to respond to these abnormal proteins, helping to destroy the cells with mutations before they can turn into cancer cells.   

We have identified common DNA changes and are testing if we can train the immune system to identify and attack them with a preventative vaccine.

Unlike other studies in this area, we are focussing on DNA changes that appear in very early (precancerous) tumours. Our goal is to develop a vaccine that can prevent as many cancers caused by Lynch syndrome as possible, not just one type.

By partnering with the nationwide Genomics England 100,000 Genomes Project, and by analysing samples donated by patients, we have already identified hundreds of potential targets through whole genome sequencing. We have also shown that some of these targets are already present in precancers.

To move forward, we need to build our confidence that these targets are not only present, but visible to the immune system. We will do this by exposing blood donated by patients to vaccine targets to see if we can measure an immune response. We also want to isolate the specific T cells (a type of immune cells) which are most reactive and check if they can reach the precancers.

Our ultimate aim is to prevent the development of all cancers in people with Lynch syndrome, rather than just focusing on improving outcomes for the most common cancers.