Neo-epitopes derived from the mutated tumor suppressor gene RNF43 as targets for T cell therapy in pancreatic cancer


RNF43 is found to be mutated in 7 to 10% of pancreatic tumors. We have observed that loss of RNF43 function has an effect on pancreatic cell proliferation and migration. We are also investigating the effect that mutations in this protein have in pancreatic cancer progression using in vitro as well as in vivo models. Within the CRC 1321, in collaboration with the group of Dirk Busch, we are identifying neo-epitopes derived from RNF43 mutations observed in patients to use them as therapeutic targets for T cell therapy in pancreatic cancer.



Publications:

Neumeyer V, Brutau-Abia A, Allgäuer M, Pfarr N, Weichert W, Falkeis-Veits C, Kremmer E, Vieth M, Gerhard M, Mejías-Luque R. Loss of RNF43 Function Contributes to Gastric Carcinogenesis by Impairing DNA Damage Response. Cell Mol Gastroenterol Hepatol. 2020 Nov 11;11(4):1071-1094. (Full text; Abstract)

Neumeyer V, Vieth M, Gerhard M, Mejías-Luque R. Mutated Rnf43 Aggravates Helicobacter Pylori-Induced Gastric Pathology. Cancers (Basel). 2019 Mar 16;11(3). pii: E372. (Full Text; Abstract)

Neumeyer V, Grandl M, Dietl A, Brutau-Abia A, Allgäuer M, Kalali B, Zhang Y, Pan KF, Steiger K, Vieth M, Anton M, Mejías-Luque R, Gerhard M. Loss of endogenous RNF43 function enhances proliferation and tumour growth of intestinal and gastric cells. Carcinogenesis. 2019 Jun 10;40(4):551-559. (Full Text; Abstract)

Quintana I, Mejías-Luque R, Terradas M, Navarro M, Piñol V, Mur P, Belhadj S, Grau E, Darder E, Solanes A, Brunet J, Capellá G, Gerhard M, Valle L. Evidence suggests that germline RNF43 mutations are a rare cause of serrated polyposis. Gut. 2018 Jan 12. (Full Text; Abstract)

Loregger A, Grandl M, Mejías-Luque R, Allgäuer M, Degenhart K, Haselmann V, Oikonomou C, Pantelis Hatzis, Janssen KP, Nitsche U, Gradl D, van den Broek O, Destree O, Neumaier M, Kalali B, Jung A, Varela I, Schmid RM, Rad R, Busch DH and Gerhard M. The stem-cell E3 ligase RNF43 displays a novel mode of Wnt inhibition downstream of (mutated) β-catenin, which is disrupted in tumors bearing RNF43 mutations. Science Signaling 2015 Sep 8;8(393):ra90. (Full Text; Abstract)