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Recurrent frameshift neoantigen vaccine elicits protective immunity with reduced tumor burden and improved overall survival in a Lynch syndrome mouse model

DNA mismatch repair deficiency drives microsatellite instability (MSI). Cells with MSI accumulate numerous frameshift mutations. Frameshift mutations affecting cancer-related genes may promote tumorigenesis and, therefore, are shared among independently arising MSI tumors. Consequently, such recurre...

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Main Authors: Gebert, Johannes (Author) , Gelincik, Ozkan (Author) , Özcan-Wahlbrink, Mine (Author) , Marshall, Jason D. (Author) , Hernandez Sanchez, Alejandro (Author) , Urban, Katharina (Author) , Long, Mark (Author) , Cortes, Eduardo (Author) , Tosti, Elena (Author) , Katzenmaier, Eva-Maria Katharina (Author) , Song, Yurong (Author) , Elsaadi, Ali (Author) , Deng, Nan (Author) , Vilar, Eduardo (Author) , Fuchs, Vera (Author) , Nelius, Nina (Author) , Yuan, Yan (Author) , Ahadova, Aysel (Author) , Sei, Shizuko (Author) , Shoemaker, Robert H. (Author) , Umar, Asad (Author) , Wei, Lei (Author) , Liu, Song (Author) , Bork, Peer (Author) , Edelmann, Winfried (Author) , Knebel Doeberitz, Magnus von (Author) , Lipkin, Steven M. (Author) , Kloor, Matthias (Author)
Format: Article (Journal)
Language:English
Published: 2 July 2021
In: Gastroenterology
Year: 2021, Volume: 161, Issue: 4, Pages: 1288-1302.e13
ISSN:1528-0012
DOI:10.1053/j.gastro.2021.06.073
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1053/j.gastro.2021.06.073
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0016508521031875
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Author Notes:Johannes Gebert, Ozkan Gelincik, Mine Oezcan-Wahlbrink, Jason D. Marshall, Alejandro Hernandez-Sanchez, Katharina Urban, Mark Long, Eduardo Cortes, Elena Tosti, Eva M. Katzenmaier, Yurong Song, Ali Elsaadi, Nan Deng, Eduardo Vilar, Vera Fuchs, Nina Nelius, Yan Yuan, Aysel Ahadova, Shizuko Sei, Robert H. Shoemaker, Asad Umar, Lei Wei, Song Liu, Peer Bork, Winfried Edelmann, Magnus von Knebel Doeberitz, Steven M. Lipkin, and Matthias Kloor
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Summary:DNA mismatch repair deficiency drives microsatellite instability (MSI). Cells with MSI accumulate numerous frameshift mutations. Frameshift mutations affecting cancer-related genes may promote tumorigenesis and, therefore, are shared among independently arising MSI tumors. Consequently, such recurrent frameshift mutations can give rise to shared immunogenic frameshift peptides (FSPs) that represent ideal candidates for a vaccine against MSI cancer. Pathogenic germline variants of mismatch repair genes cause Lynch syndrome (LS), a hereditary cancer syndrome affecting approximately 20-25 million individuals worldwide. Individuals with LS are at high risk of developing MSI cancer. Previously, we demonstrated safety and immunogenicity of an FSP-based vaccine in a phase I/IIa clinical trial in patients with a history of MSI colorectal cancer. However, the cancer-preventive effect of FSP vaccination in the scenario of LS has not yet been demonstrated.
Item Description:Gesehen am 27.07.2021
Physical Description:Online Resource
ISSN:1528-0012
DOI:10.1053/j.gastro.2021.06.073

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