People with Lynch syndrome inherit a high risk of several cancers, and their tumours carry distinctive protein fragments produced by a common DNA copying error. The experimental vaccine NOUS-209 trains the immune system to recognise 209 of these shared fragments. Sequencing 73 bowel and bladder tumours from 58 people with Lynch syndrome showed the vaccine targets were plentiful in both tumour types and in first as well as later cancers; over time the immune system appeared to clear the most recognisable ones, yet every new tumour produced fresh targets the vaccine could hit. The findings suggest NOUS-209 might help prevent both first and repeat Lynch syndrome cancers, including bladder cancer, not only bowel cancer.