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 immunologically 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 of which HPV epitopes are present on tumor cells using a specialized mass spectrometry (MS) approach, and on validating them for immunogenicity and their potential to elicit functional T cell responses.

FUTURE OUTLOOK
Nearly every sexually active individual acquire a high-risk HPV infection during their lifetime, but only 1-2% develop persistent infection, so there must be differences in the induction of effective immune responses. One project in the lab investigates effects of HPV on the cellular antigen processing machinery, and the resulting effects on the epitope repertoire.
Future aims are to examine various vaccine delivery and adjuvant formulations. All of these studies will contribute to an optimal formulation of a therapeutic vaccine, aiming at the effective induction of adaptive immune responses in persistently HPV-infected patients. Our high-sensitivity approach of epitope detection can be used as a platform technology for other infectious diseases and malignancies. It has already been shown to be capable of detecting tumor-specific mutation-derived tumor neo-epitopes.

Contact

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

Selected Publications

  • 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.
  • Khallouf H., Grabowska, A.K., Riemer, A.B. (2014). Therapeutic vaccine strategies against HPV. Vaccines, 2(2):422-462. doi: 10.3390/vaccines2020422.
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