Abstract CN01-03: Frameshift peptide vaccination: Towards cancer prevention in Lynch syndrome

Abstract

Abstract Lynch syndrome is one of the most common hereditary cancer syndromes. It is caused by germ line mutations of DNA mismatch repair genes and predisposes affected individuals to the development of colorectal cancer and extracolonic malignancies with a lifetime risk of over 50%. Lynch syndrome-associated cancers show the high-level microsatellite instability (MSI-H) phenotype and are characterized by signs of a pronounced local anti-tumoral immune response, suggesting that the immune system plays an active role in the surveillance and natural history of these cancers. The progression of MSI-H cancers is triggered by mutations in microsatellite sequences within gene-encoding regions, which can cause shifts of the translational reading frame and lead to the generation of immunogenic frameshift peptides (FSP) at the carboxy-terminal end of the respective proteins. FSP-specific immune responses have been observed frequently in MSI-H cancer patients and Lynch syndrome mutation carriers. We have therefore initiated a clinical phase I/IIa vaccination trial that evaluates vaccination with a combination of three FSP antigens in patients with MSI-H colorectal cancer, UICC stage III and IV. Preliminary data demonstrate that no treatment-associated severe adverse events have been observed after FSP vaccination. Moreover, significant T cell and humoral immune responses against FSP antigens were induced in the majority of vaccinated patients. The observation of strong FSP-specific immune responses in vaccinated patients suggests that FSP-based vaccination may represent a novel option for the treatment of MSI-H colorectal cancer patients. Moreover, FSP vaccination may be used for tumor prevention in Lynch syndrome mutation carriers in the future. Citation Format: Matthias Kloor, Miriam Reuschenbach, Julia Karbach, Reza Rafiyan, Salah-Eddin Al-Batran, Claudia Pauligk, Elke Jaeger, Magnus von Knebel Doeberitz. Frameshift peptide vaccination: Towards cancer prevention in Lynch syndrome. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN01-03.