Development of a vaccine for MSI cancers

Our research showed that the evolution of MSI cancers results in the outgrowth of cell clones with similar mutation patterns. Certain recurrent mutations at coding microsatellites are driver events of MSI tumor development and at the same time give rise to novel frameshift peptide (FSP) neoantigens.

We used the concept of driver mutation-induced FSP neoantigens to generate a first-in-human vaccine. In a phase I/IIa clinical trial (clinicaltrials.gov/ct2/show/NCT01461148), we provided proof-of-concept that vaccination with 3 shared FSP neoantigens leads to strong induction of cellular and humoral immune response in patients with MSI cancer. No vaccination-related severe systemic side effects were observed in any of the vaccinated patients. In future projects, we plan to analyze the preventive capacity of FSP-vaccination for Lynch syndrome patients.