Preclinical Models

We have a broad expertise in in vivo antibody treatments (therapeutic antibodies or depletion of specific cell populations for mode of action analysis), combination therapy (checkpoint inhibitors, chemotherapy, local radiotherapy via an Orthovoltage X-Ray device) and the use of specific transgenic models for diverse biological questions. In addition, we apply various immunological methods such as IFN-γ, ELISpot, tetramer staining and intracellular cytokine FACS for immunomonitoring and we apply multi-colour staining protocols (up to 18 colours) for phenotypic/functional characterisation of the tumor microenviroment. We work closely together with other technology platforms to integrate advanced histology & cryo-IF, q-RT-PCR or state-of-the-art sequencing (as scSeq) into our preclinical studies.

Investigating immunologic mechanisms in vivo is a fundamental part of translational medical research. Particularly important areas of investigation at TRON are the in vivo efficacy of T cell vaccines and combinatorial approaches, furthermore the set-up and characterization of tumor models to address this. We are also interested in nanoparticles and liposome formulations as therapeutics and immune escape mechanisms. To this end, we employ a broad repertoire of syngeneic tumor models where diverse transgenic variants are available (e.g. to model immune escape) as well as orthotopic & metastases models or xenograft. Our models are often investigated via in vivo luminescence and fluorescence, and we are continuously advancing biotechniques to support this.

Tools and Platforms

  • Syngeneic & xenograft mouse models
  • In vivo Imaging
  • Combination therapy (ICI, Chemotherapy, local Radiotherapy)
  • ELISpot & functional assays
  • Tumor microenvironment analysis
  • Multicolor flow cytometry

Key Contributions and Publications

  • Salomon N, Vascotto F, Selmi A, Vormehr M, Quinkhardt J, Bukur T, Schrörs B, Löwer M, Diken M, Türeci Ö, Sahin U, Kreiter S. (2020) A liposomal RNA vaccine inducing neoantigen-specific CD4+ T cells augments the antitumor activity of local radiotherapy in mice. Oncoimmunology. 9:1771925. DOI: PUBMED.
  • Kranz LM, Diken M, Haas H, Kreiter S, Loquai C, Reuter KC, Meng M, Fritz D, Vascotto F, Hefesha H, Grunwitz C, Vormehr M, Hüsemann Y, Selmi A, Kuhn AN, Buck J, Derhovanessian E, Rae R, Attig S, Diekmann J, Jabulowsky RA, Heesch S, Hassel J, Langguth P, Grabbe S, Huber C, Türeci Ö, Sahin U. (2016) Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature. 534(7607):396-40. DOI; PUBMED
  • Selmi A, Vascotto F, Kautz-Neu K, Türeci Ö, Sahin U, von Stebut E, Diken M, Kreiter S. (2016) Uptake of synthetic naked RNA by skin-resident dendritic cells via macropinocytosis allows antigen expression and induction of T-cell responses in mice. Cancer Immunol Immunother. 65(9):1075-83. DOI; PUBMED
  • Castle JC, Kreiter S, Diekmann J, Löwer M, van de Roemer, Niels, Graaf J de, Selmi A, Diken M, Boegel S, Paret C, Koslowski M, Kuhn AN, Britten CM, Huber C, Türeci O, Sahin U. (2012) Exploiting the mutanome for tumor vaccination. Cancer Research. 72:1081-1091. DOI; PUBMED
  • Diken, M., Kreiter, S., Selmi, A., Britten, C.M., Huber, C., Türeci, Ö., and Sahin, U. (2011) Selective uptake of naked vaccine RNA by dendritic cells is driven by macropinocytosis and abrogated upon DC maturation.Gene Ther. 18(7):702-8.  DOIPUBMED

More Technologies and Platforms