Prof. Dr. med. Matthias Kloor

As a physician scientist I have been working in the field of molecular pathology, tumor immunology, and pathogenesis of hereditary cancer for more than a decade. My research interests are dedicated to molecular models of tumor formation and their transfer into the clinical application, with a main focus on tumor immunology and immunological approaches for cancer prevention and treatment. My research during the last 10 years as leader of the research group ‘Immune biology of microsatellite-unstable cancer’ has been focused on the identification of relevant neoantigens specifically generated in microsatellite-unstable (MSI-H) cancers. These research activities have led to the first-in-human clinical trial examining a frameshift peptide neoantigen vaccine in MSI-H cancer patients. I complement the studies on cancer vaccines by examining mechanisms of immune evasion that allow MSI-H tumors to develop in spite of pronounced anti-tumoral immune responses.

Currently, I am leading the DKFZ site of the NCI-funded CAP-IT U54 project aiming at developing next-generation cancer immunoprevention approaches. CAP-IT CRI has assembled a collaborative team of scientists and researchers from various institutions, such as Weill Cornell Medicine, DKFZ (German Cancer Research Center), Sloan Kettering Institute, Cornell Engineering, Dana-Farber Cancer Institute, and the Broad Institute. The CAP-IT CRI will develop state-of-the-art LNP RNA immunoprevention and immune interception vaccines and provide a technologically powerful platform to jumpstart additional CAP-IT CRI LNP RNA vaccine projects.

It is anticipated that CAP-IT CRI will propel both Lynch syndrome and lung non-solid nodules (NSN) vaccines to NCI PREVENT and CP-CTNET clinical trials within the next 5 years and FDA approval/clinical translation within ten years. I am also the Project Leader of the INDICATE Network that has been established to understand the role of HLA genotype in determining cancer risk among Lynch syndrome carriers.

Publications (selected) / Output

Song Y, Loomans-Kropp H, Baugher RN, Somerville B, Baxter SS, Kerr TD, Plona TM, Mellott SD, Young TB, Lawhorn HE, Wei L, Hu Q, Liu S, Hutson A, Pinto L, Potter JD, Sei S, Gelincik O, Lipkin SM, Gebert J, Kloor M, Shoemaker RH. Frameshift mutations in peripheral blood as a biomarker for surveillance of lynch syndrome. J Natl Cancer Inst. 2024 Mar 11:djae060. Online ahead of print. PMID: 38466935

Sei S, Ahadova A, Keskin DB, Bohaumilitzky L, Gebert J, von Knebel Doeberitz M, Lipkin SM, Kloor M. Lynch syndrome cancer vaccines: A roadmap for the development of precision immunoprevention strategies. Front Oncol. 2023 Mar 22;13:1147590. eCollection 2023. PMID: 37035178

Ahadova A, Stenzinger A, Seppälä T, Hüneburg R, Kloor M, Bläker H; Lynpath Investigators. A “Two-in-One Hit” Model of Shortcut Carcinogenesis in MLH1 Lynch Syndrome Carriers. Gastroenterology. 2023 Jul;165(1):267-270.e4. Epub 2023 Mar 11. PMID: 36907525

Witt J, Haupt S, Ahadova A, Bohaumilitzky L, Fuchs V, Ballhausen A, Przybilla MJ, Jendrusch M, Seppälä TT, Fürst D, Walle T, Busch E, Haag GM, Hüneburg R, Nattermann J, von Knebel Doeberitz M, Heuveline V, Kloor M. A simple approach for detecting HLA-A*02 alleles in archival formalin-fixed paraffin-embedded tissue samples and an application example for studying cancer immunoediting. HLA. 2023 Jan;101(1):24-33. Epub 2022 Oct 25. PMID: 36251018

 

Ahadova A, Witt J, Haupt S, Gallon R, Hüneburg R, Nattermann J, Ten Broeke S, Bohaumilitzky L, Hernandez-Sanchez A, Santibanez-Koref M, Jackson MS, Ahtiainen M, Pylvänäinen K, Andini K, Grolmusz VK, Möslein G, Dominguez-Valentin M, Møller P, Fürst D, Sijmons R, Borthwick GM, Burn J, Mecklin JP, Heuveline V, von Knebel Doeberitz M, Seppälä T, Kloor M. Is HLA type a possible cancer risk modifier in Lynch syndrome? Int J Cancer. 2023 May 15;152(10):2024-2031. Epub 2022 Oct 14. PMID: 36214792

 

Hernandez-Sanchez A, Grossman M, Yeung K, Sei SS, Lipkin S, Kloor M. Vaccines for immunoprevention of DNA mismatch repair deficient cancers. J Immunother Cancer. 2022 Jun;10(6):e004416. PMID: 35732349
Bohaumilitzky L, Kluck K, Hüneburg R, Gallon R, Nattermann J, Kirchner M, Kristiansen G, Hommerding O, Pfuderer PL, Wagner L, Echterdiek F, Kösegi S, Müller N, Fischer K, Nelius N, Hartog B, Borthwick G, Busch E, Haag GM, Bläker H, Möslein G, von Knebel Doeberitz M, Seppälä TT, Ahtiainen M, Mecklin JP, Bishop DT, Burn J, Stenzinger A, Budczies J, Kloor M, Ahadova A. The Different Immune Profiles of Normal Colonic Mucosa in Cancer-Free Lynch Syndrome Carriers and Lynch Syndrome Colorectal Cancer Patients. Gastroenterology. 2022

Mar;162(3):907-919.e10. Epub 2021 Dec 2. PMID: 34863788

Gebert J, Gelincik O, Oezcan-Wahlbrink M, Marshall JD, Hernandez-Sanchez A, Urban K, Long M, Cortes E, Tosti E, Katzenmaier EM, Song Y, Elsaadi A, Deng N, Vilar E, Fuchs V, Nelius N, Yuan YP, Ahadova A, Sei S, Shoemaker RH, Umar A, Wei L, Liu S, Bork P, Edelmann W, von Knebel Doeberitz M, Lipkin SM, Kloor M. Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity With Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model. Gastroenterology. 2021 Oct;161(4):1288-1302.e13. Epub 2021 Jul 2. PMID: 34224739

 

Busch E, Ahadova A, Kosmalla K, Bohaumilitzky L, Pfuderer PL, Ballhausen A, Witt J, Wittemann JN, Bläker H, Holinski-Feder E, Jäger D, von Knebel Doeberitz M, Haag GM, Kloor M. Beta-2-microglobulin Mutations Are Linked to a Distinct Metastatic Pattern and a Favorable Outcome in Microsatellite-Unstable Stage IV Gastrointestinal Cancers. Front Oncol. 2021 Jun 8;11:669774. eCollection 2021. PMID: 34168989

 

Ballhausen A, Przybilla MJ, Jendrusch M, Haupt S, Pfaffendorf E, Seidler F, Witt J, Hernandez Sanchez A, Urban K, Draxlbauer M, Krausert S, Ahadova A, Kalteis MS, Pfuderer PL, Heid D, Stichel D, Gebert J, Bonsack M, Schott S, Bläker H, Seppälä T, Mecklin JP, Ten Broeke S, Nielsen M, Heuveline V, Krzykalla J, Benner A, Riemer AB, von Knebel Doeberitz M, Kloor M. The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution. Nat Commun. 2020 Sep 21;11(1):4740. PMID: 32958755

 

Kloor M, Reuschenbach M, Pauligk C, Karbach J, Rafiyan MR, Al-Batran SE, Tariverdian M, Jäger E, von Knebel Doeberitz M. A Frameshift Peptide Neoantigen-Based Vaccine for Mismatch Repair-Deficient Cancers: A Phase I/IIa Clinical Trial. Clin Cancer Res. 2020 Sep 1;26(17):4503-4510. Epub 2020 Jun 15. PMID: 32540851

Ozcan M, Janikovits J, von Knebel Doeberitz M, Kloor M. Complex pattern of immune evasion in MSI colorectal cancer. Oncoimmunology. 2018 Mar 26;7(7):e1445453. PMID: 29900056.

Ahadova A, Gallon R, Gebert J, Ballhausen A, Endris V, Kirchner M, Stenzinger A, Burn J, von Knebel Doeberitz M, Bläker H, Kloor M. Three molecular pathways model colorectal carcinogenesis in Lynch syndrome. Int J Cancer. 2018 Jul 1. PMID: 29424427

Janikovits J, Müller M, Krzykalla J, Körner S, Echterdiek F, Lahrmann B, Grabe N, Schneider M, Benner A, Doeberitz MVK, Kloor M. High numbers of PDCD1 (PD-1)-positive T cells and B2Mmutations in microsatellite-unstable colorectal cancer. Oncoimmunology. 2017 Nov 6;7(2):e1390640. PMID: 29308317.

Echterdiek F, Janikovits J, Staffa L, Müller M, Lahrmann B, Frühschütz M, Hartog B, Nelius N, Benner A, Tariverdian M, von Knebel Doeberitz M, Grabe N, Kloor M. Low density of FOXP3-positive T cells in normal colonic mucosa is related to the presence of beta2-microglobulin mutations in Lynch syndrome-associated colorectal cancer. Oncoimmunology. 2015 Nov 11;5(2):e1075692. PMID: 27057447.

Ahadova A, von Knebel Doeberitz M, Bläker H, Kloor M. CTNNB1-mutant colorectal carcinomas with immediate invasive growth: a model of interval cancers in Lynch syndrome.Fam Cancer. 2016 Oct;15(4):579-86. PMID: 26960970.

Kloor M, von Knebel Doeberitz M. The Immune Biology of Microsatellite-Unstable Cancer.Trends Cancer. 2016 Mar;2(3):121-133. Review. PMID: 28741532.

Staffa L, Echterdiek F, Nelius N, Benner A, Werft W, Lahrmann B, Grabe N, Schneider M, Tariverdian M, von Knebel Doeberitz M, Bläker H, Kloor M. Mismatch repair-deficient crypt foci in Lynch syndrome–molecular alterations and association with clinical parameters.PLoS One. 2015 Mar 27;10(3):e0121980. PMID: 25816162

Surmann EM, Voigt AY, Michel S, Bauer K, Reuschenbach M, Ferrone S, von Knebel Doeberitz M, Kloor M. Association of high CD4-positive T cell infiltration with mutations in HLA class II-regulatory genes in microsatellite-unstable colorectal cancer.Cancer Immunol Immunother. 2015 Mar;64(3):357-66. PMID: 25445815

Woerner SM, Tosti E, Yuan YP, Kloor M, Bork P, Edelmann W, Gebert J. Detection of coding microsatellite frameshift mutations in DNA mismatch repair-deficient mouse intestinal tumors.Mol Carcinog. 2015 Nov;54(11):1376-86. PMID: 25213383

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

Capper D, Voigt A, Bozukova G, Ahadova A, Kickingereder P, von Deimling A, von Knebel Doeberitz M, Kloor M. BRAF V600E-specific immunohistochemistry for the exclusion of Lynch syndrome in MSI-H colorectal cancer.Int J Cancer. 2013 Oct 1;133(7):1624-30. PMID: 23553055

Kloor M, Huth C, Voigt AY, Benner A, Schirmacher P, von Knebel Doeberitz M, Bläker H. Prevalence of mismatch repair-deficient crypt foci in Lynch syndrome: a pathological study.Lancet Oncol. 2012 Jun;13(6):598-606. PMID: 22552011

Tikidzhieva A, Benner A, Michel S, Formentini A, Link KH, Dippold W, von Knebel Doeberitz M, Kornmann M, Kloor M. Microsatellite instability and Beta2-Microglobulin mutations as prognostic markers in colon cancer: results of the FOGT-4 trial.Br J Cancer. 2012 Mar 13;106(6):1239-45. PMID: 22353804

Bauer K, Michel S, Reuschenbach M, Nelius N, von Knebel Doeberitz M, Kloor M. Dendritic cell and macrophage infiltration in microsatellite-unstable and microsatellite-stable colorectal cancer.Fam Cancer. 2011 Sep;10(3):557-65. doi: 10.1007/s10689-011-9449-7. PMID: 21598004

Kloor M, Voigt AY, Schackert HK, Schirmacher P, von Knebel Doeberitz M, Bläker H. Analysis of EPCAM protein expression in diagnostics of Lynch syndrome.J Clin Oncol. 2011 Jan 10;29(2):223-7. doi: 10.1200/JCO.2010.32.0820. Epub 2010 Nov 29. PMID: 21115857

Kloor M, Michel S, von Knebel Doeberitz M. Immune evasion of microsatellite unstable colorectal cancers. Int J Cancer. 2010 Sep 1;127(5):1001-10. doi: 10.1002/ijc.25283. Review. PMID: 20198617

Michel S, Linnebacher M, Alcaniz J, Voss M, Wagner R, Dippold W, Becker C, von Knebel Doeberitz M, Ferrone S, Kloor M. Lack of HLA class II antigen expression in microsatellite unstable colorectal carcinomas is caused by mutations in HLA class II regulatory genes.Int J Cancer. 2010 Aug 15;127(4):889-98. PMID: 20013806

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

Michel S, Kloor M, Singh S, Gdynia G, Roth W, von Knebel Doeberitz M, Schirmacher P, Bläker H. Coding microsatellite instability analysis in microsatellite unstable small intestinal adenocarcinomas identifies MARCKS as a common target of inactivation.Mol Carcinog. 2010 Feb;49(2):175-82. PMID: 19852062

Kloor M. Lymphocyte infiltration and prognosis in colorectal cancer.Lancet Oncol. 2009 Sep;10(9):840-1. PMID: 19717085

Roeckel N, Woerner SM, Kloor M, Yuan YP, Patsos G, Gromes R, KopitzJ, Gebert J. High frequency of LMAN1 abnormalities in colorectal tumors with microsatellite instability. Cancer Res. 2009 Jan 1;69(1):292-9. PMID:19118014

Michel S, Benner A, Tariverdian M, Wentzensen N, Hoefler P, Pommerencke T, Grabe N, von Knebel Doeberitz M, Kloor M. High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability.Br J Cancer. 2008 Dec 2;99(11):1867-73. PMID: 18985040

Korff S, Woerner SM, Yuan YP, Bork P, von Knebel Doeberitz M, Gebert J. Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability. BMC Cancer. 2008 Nov 10;8:329. PMID: 19000305

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

Kloor M, Michel S, Buckowitz B, Rüschoff J, Büttner R, Holinski-Feder E, Dippold W, Wagner R, Tariverdian M, Benner A, Schwitalle Y, Kuchenbuch B, von Knebel Doeberitz M. Beta2-microglobulin mutations in microsatellite unstable colorectal tumors.Int J Cancer. 2007 Jul 15;121(2):454-8. PMID: 17373663

Woerner SM, Kloor M, von Knebel Doeberitz M, Gebert JF. Microsatellite instability in the development of DNA mismatch repair deficient tumors.Cancer Biomark. 2006;2(1-2):69-86. Review. PMID: 17192061

Kloor M, Becker C, Benner A, Woerner SM, Gebert J, Ferrone S, von Knebel Doeberitz M. Immunoselective pressure and human leukocyte antigen class I antigen machinery defects in microsatellite unstable colorectal cancers.Cancer Res. 2005 Jul 15;65(14):6418-24. PMID: 16024646

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MATTHIAS KLOOR