Immuno-Oncology

PD Dr. Dafne Müller

Research overview

Cancer development is accompanied by the generation of tumour evasion mechanisms from the immune system. The challenge of cancer immunotherapy consists in enabling the immune system again to recognize and eliminate the tumour cells. A key feature is to overcome the immunosuppressive conditions in the tumour microenvironment. This can be achieved by interfering with the complex regulatory network of the immune system, shifting the balance towards supporting and driving an anti-tumour response. Here, in particular members of the B7/CD28-superfamily, TNF/TNFR-superfamily and cytokines/common γ-chain receptor family have shown great potential. We are interested in exploring how tumour-directed delivery and defined combinations of such immunomodulatory molecules can enhance the immune response in the tumour microenvironment leading to novel therapeutic strategies.

Targeted strategies with bi- and trifunctional antibody-fusion proteins

Tumour targeting can be achieved by antibodies binding specifically to tumour associated antigens (TAA). This makes recombinant antibodies a valuable tool for diverse targeted approaches. For example, bispecific antibodies (TAAxCD3) can retarget effector cells to tumour cells, inducing artificially an antitumor immune response. Also, ligands or cytokines fused to recombinant antibodies can be directed to and presented at the tumour cell surface to immune cells, modulating their response. Certainly, both approaches can also be combined. In order to explore the potential and improve the efficacy of such molecules we design different formats of bi- and trifunctional antibody-fusion proteins, focusing on optimized presentation and a combined mode of action. Analysis are carried out in 2D- and 3D-coculture settings with tumour cells/immune cells in vitro and in tumour mouse models in vivo.

Publications

Selected research articles

Review articles

  • Müller D (2015) Antibody fusions with immunomodulatory proteins for cancer therapy.Pharmacol Ther. 154:57-66. doi: 10.1016/j.pharmthera.2015.07.001. 
  • Müller D (2014) Antibody fusion proteins for cancer immunotherapy: an update on recent developments. BioDrugs. 28(2):123-31. doi: 10.1007/s40259-013-0069-7.
  • Müller D (2012) Targeted cancer immunotherapy: mimicking physiological trans-presentation of IL-15. OncoImmunology 1(7):1213-1214. doi: 10.4161/onci.20824.
  • Müller D, Kontermann RE (2010) Bispecific antibodies for cancer immunotherapy: Current perspectives. 24(2):89-98. doi: 10.2165/11530960-000000000-00000.
  • Muller D, Kontermann RE (2007) Recombinant bispecific antibodies for cellular cancer immunotherapy. Curr Opin Mol Ther. 9(4):319-26.

Book chapters

  • Siegemund M, Beha N, Müller D. (2018) Production, Purification, and Characterization of Antibody-TNF Superfamily Ligand Fusion Proteins.In: Antibody Engineering, Methods and Protocols. 3th  Nevoltris and P. Chames (Eds.), Springer Nature, New York, pp.351-364.
  • Müller, D. and Kontermann, R.E. (2014) Bispecific Antibodies In: Handbook of Therapeutic Antibodies. 2thDübel S. (Hrsg.), WILEY-VCH Verlag, Weinheim. Vol.I pp.267-293
  • Müller, D. & Kontermann, R.E. (2011) Recombinant bispecific antibodies for cancer therapy. In: Antibody Expression and Production (Cell Engineering 7), Al-Rubeai M. (Ed.), Springer-Verlag, Heidelberg, pp.235-250.
  • Müller, D. & Kontermann, R.E. (2011) Diabodies, single-chain diabodies and their derivatives. In: „Bispecific Antibodies“, Kontermann R.E. (Ed.), Springer-Verlag, Heidelberg, pp. 83-100.
  • Müller D & Gerspach J (2010) Antibody-Cytokine Fusion Proteins with Members of the TNF-Family. In: Antibody Engineering R Kontermann and S. Dübel (eds.) Springer-Verlag Berlin Heidelberg. 2 pp. 113-126.

Lab members

PD Dr. Dafne Müller (PI)
Katrin Lazar (Postdoc)
Nathalie Roßmanith (Master student)
Meng Xie (Master student)
Sarah Vettermann (Bachelor student)

Open positions

Applications of students and scientists interested in biomedical engineering and cancer immunotherapy are always welcome! Please send your CV and a short summary of your research interests to mailto iconDr. Dafne Müller

A PhD position is now available in the group.

Funding

Our group has received funding from: DFG, German Cancer Aid and industry collaboration.

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