Junior Research Group Immunotherapy and -prevention
PD Dr. Dr. Angelika Riemer
At least 20% of human malignancies are caused by consequences of persistent infections. Cancers caused by infectious agents (e.g. human papillomavirus – HPV) are attractive targets for cancer vaccination approaches, as they provide the opportunity to target antigens that are immunological non-self.
Vaccination can be prophylactic, inducing antibodies that prevent infection, or therapeutic, stimulating the cellular immune system into eradicating established disease. Prophylactic immunization against HPV has become the paradigm for cancer immunoprevention. Unfortunately, current HPV vaccines have no therapeutic effect on existing infections.
The aim of therapeutic vaccination is to stimulate the immune system into recognizing and destroying malignant cells. Cytotoxic T cells (CTL) kill infected cells after recognizing bits of viral proteins, so-called epitopes, which are presented on human leukocyte antigen (HLA) molecules on the cell surface. There are thousands of different HLA types, all presenting different epitopes. As every human being has a different set of HLA molecules, epitopes for all major HLA groups need to be defined.
The overall aim of this group is to generate a therapeutic cancer vaccine against HPV-induced malignancies that is applicable to everyone regardless of a person’s HLA type. We are currently working on the precise identification which HPV epitopes are present on tumor cells by a mass spectrometry (MS) approach, and on assessing their immunogenicity by functional immunological assays.
Grabowska, A.K., Kaufmann, A.M., Riemer, A.B. (2015). Identification of promiscuous HPV16-derived T helper cell epitopes for therapeutic HPV vaccine design. Int. J. Cancer, 136(1), 212-24. doi: 10.1002/ijc.28968. Epub 2014 May 27.
Schumacher, T., Bunse, L., Sahm, F., Pusch, S., Quandt, J., Wiestler, B., Oezen, I., Menn, O., Osswald, M., Grabowska, A.K., Eichmueller, S., Riemer, A.B., Friese, M., Beckhove, P., von Deimling, A., Wick, W., Ott, M., Keil, M., Balss, J., Rauschenbach, K., Vogler, I., Diekmann, J., Sahin, U., Stevanovic, S., Trautwein, N., Okun, J. & Platten, M. (2014). A vaccine targeting mutant IDH1 induces antitumor immunity. Nature, 512(7514):324-7. doi:10.1038/nature13387.
Zhang, G.L., Riemer, A.B., Keskin, D.B., Chitkushev, L., Reinherz, E.L. & Brusic, V. (2014). HPVdb: a data mining system for knowledge discovery in human papillomavirus with applications in T cell immunology and vaccinology. Database, article ID bau031; doi:10.1093/database/bau031
Riemer, A.B., Keskin D.B., Zhang G., Handley M., Anderson K.S., Brusic V., Reinhold B. & Reinherz E.L. (2010). A conserved E7-derived CTL epitope expressed on human papillomavirus-16 transformed HLA-A2+ human epithelial cancers. J. Biol. Chem., 285(38), 29608-22