The fact that we and others were able to identify recurrent driver mutations that are shared by most MSI cancers enables the development and design of immune prevention approaches against MSI cancer. Particularly in the hereditary setting, where patients are predisposed to developing MSI cancers at younger age and secondary prevention approaches are only available for few cancer types and have a limited preventive capacity, it is important to develop primary preventive strategies for patients with cancer predisposition.
We are working on the precise characterization of the immunological consequences of MSI driver mutations. We have developed novel tools to dissect the driver mutation patterns of MSI cancers in high resolution, allowing us to comprehensively map MSI tumor neoantigens (frameshift peptides, FSPs). Following our basic research on MSI neoantigens, we were able to translate the approach of FSP neoantigen vaccines into a first proof-of-concept clinical phase I/IIa trial, which has successfully been completed at the Krankenhaus Nordwest in Frankfurt.
Publications / Output
Kloor M, von Knebel Doeberitz M. The Immune Biology of Microsatellite-Unstable Cancer.Trends Cancer. 2016 Mar;2(3):121-133. Review. PMID: 28741532.
Reuschenbach M, Dörre J, Waterboer T, Kopitz J, Schneider M, Hoogerbrugge N, Jäger E, Kloor M, von Knebel Doeberitz M. A multiplex method for the detection of serum antibodies against in silico-predicted tumor antigens.Cancer Immunol Immunother. 2014 Dec;63(12):1251-9. PMID: 25143232
Brenner H, Kloor M, Pox CP. Colorectal cancer.Lancet. 2014 Apr 26;383(9927):1490-1502. PMID: 24225001
Kloor M, Staffa L, Ahadova A, von Knebel Doeberitz M. Clinical significance of microsatellite instability in colorectal cancer.Langenbecks Arch Surg. 2014 Jan;399(1):23-31. Review. PMID: 24048684
von Knebel Doeberitz M, Kloor M. Towards a vaccine to prevent cancer in Lynch syndrome patients.Fam Cancer. 2013 Jun;12(2):307-12. doi: 10.1007/s10689-013-9662-7. Review. PMID: 23760517
Reuschenbach M, Kloor M, Morak M, Wentzensen N, Germann A, Garbe Y, Tariverdian M, Findeisen P, Neumaier M, Holinski-Feder E, von Knebel Doeberitz M. Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome.Fam Cancer. 2010 Jun;9(2):173-9. PMID: 19957108
Schwitalle Y, Kloor M, Eiermann S, Linnebacher M, Kienle P, Knaebel HP, Tariverdian M, Benner A, von Knebel Doeberitz M. Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers. 2008 Apr;134(4):988-97. PMID: 18395080