Junior Research Group Immunotherapy and Immunoprevention

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 for therapeutic vaccine development.
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 presented on tumor cells by a mass spectrometry (MS) approach. This is important as HPV employs various immune evasion mechanisms, and not every possible viral epitope will be presented on the tumor cell surface. Identified epitopes are tested for immunogenicity; we examine various vaccine delivery and adjuvant formulations. Moreover, we are developing a tumor model that allows assessing the efficiency of our vaccines.

FUTURE OUTLOOK:
Future aims are to use the new tumor model to investigate ways of improving the trafficking of vaccination induced T cells to the tumor site. As our approach of epitope identification is highly sensitive, we will also apply to a new area of immunotherapy research: the identification of tumor-mutation-derived neoepitopes. These epitopes offer the chance of specifically attacking tumor cells, without harming healthy tissues. All these studies will contribute to an optimal formulation of therapeutic vaccines, aiming at the effective induction of adaptive immune responses in cancer patients.

Contact

PD Dr. Dr. Angelika Riemer
Immunotherapy and Immunoprevention (F130)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 3820

Selected Publications

  • Steinbach, A., Winter, J., Reuschenbach, M., Blatnik, R., Klevenz, A., Bertrand, M., Hoppe, S., von Knebel Doeberitz, M., Grabowska, A.K., Riemer, A.B. (2017). ERAP1 overexpression in HPV-induced malignancies: a possible novel immune evasion mechanism. OncoImmunology, 6(7):e1336594. doi: 10.1080/2162402X.2017.1336594.
  • Dekhtiarenko, I., Ratts, R.B., Blatnik, R., Lee, L.N., Fischer, S., Borkner, L., Oduro, J.D., Marandu, T.F., Hoppe, S., Ruzsics, Z., Sonnemann, J.K., Mansouri, M., Meyer, C., Lemmermann, N.A., Holtappels, R., Arens, R., Klenerman, P., Früh, K., Reddehase, M.J., Riemer, A.B., Cicin-Sain, L. (2016). Peptide processing is critical for T-cell memory inflation and may be optimized to improve immune protection by CMV-based vaccine vectors. PLoS Pathogens, 12(12):e1006072. doi: 10.1371/journal.ppat.1006072.
  • 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.
  • 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.
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