Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancer, as well as other types of tumours. At present, prevention is mainly based on clinical surveillance, particularly through regular colonoscopies, and in some cases also on preventive surgery or other risk‑reduction strategies. These measures remain essential, but in recent years an innovative line of research has emerged: the development of vaccines to prevent cancer in people with Lynch syndrome.
A new cancer prevention strategy in Lynch syndrome: how do these vaccines work?
The scientific basis of this approach lies in the fact that the genetic alterations characteristic of Lynch syndrome promote the accumulation of mutations that can generate abnormal proteins, known as neo‑peptides or neoantigens, which are shared across Lynch‑associated tumours. These molecules can be recognised by the immune system and therefore represent highly attractive targets for the development of vaccines capable of training the body’s defences to identify and eliminate altered cells before they progress to a tumour.
One of the pioneering studies in this field is led by Dr Jolanda de Vries in Nijmegen, using a preventive vaccination strategy based on autologous dendritic cells. This study provided a highly relevant proof of concept, showing that it is possible to induce neoantigen‑specific T lymphocytes associated with Lynch syndrome and that this immune response can be linked to favourable long‑term outcomes.
Preventive vaccines: international advances and research at Hospital Clínic‑IDIBAPS
More recently, the international Nous‑209 study has strengthened this field with very promising results. In this phase 1b/2 trial, conducted in 45 individuals with Lynch syndrome, the vaccine showed a favourable safety profile, with no serious adverse events related to the intervention. In addition, specific immune responses were observed in 100% of evaluable participants, and these responses remained detectable after one year in most cases. These data represent an important step forward, as they demonstrate that it is possible to activate a strong and sustained immune response in this context.
At Hospital Clínic‑IDIBAPS, this line of research is also progressing through the DELAY project, an immunoprevention strategy based on autologous dendritic cells loaded with neo‑peptides derived from Lynch syndrome. This project builds on previous work identifying vaccine targets and exemplifies our centre’s commitment to translational research focused on prevention. In this development, the role of the Immunology Department is key, both in the biological foundations of the project and in its potential future clinical application.
At an international level, other groups are also driving this field forward. In Oxford, the LynchVax programme, led by Dr David Church and funded by Cancer Research UK, is working to identify very early mutations and turn them into the basis of a future preventive vaccine based on messenger RNA. All of this confirms that we are facing a rapidly expanding field, with strong scientific foundations and real potential to transform the prevention of hereditary cancer in the coming years.
