Preventive dendritic cell vaccination in healthy Lynch syndrome mutation carriers

Abstract

Background: Lynch syndrome (LS) is an autosomal dominantly inherited syndrome caused by monoallelic germline aberrations affecting one of the DNA mismatch repair (MMR) genes. Defects in the DNA MMR pathway underlie the development of microsatellite instability in LS-associated cancer. The cumulative risk of colorectal cancer varies between 10-80% and is strongly associated with the causative germline defect. MMR deficiency in tumor DNA causes shifts in the translational reading frame resulting in the production of altered peptides, called neopeptides. These are considered ‘foreign’ by the immune system. This was the rationale for a preventive neoantigen-based vaccination study with dendritic cells (DCs). DCs are the antigen-presenting cells of our immune system as a result of their naive T cell priming and T cell activation capabilities.