Oncoimmunology

Dr. Dafne Müller

Cancer development is accompanied by the generation of evasion mechanisms, hiding the tumor cells from the immune system. The challenge of cancer immunotherapy consists in resolving this unfavorable situation by activating and directing our defense system to eliminate the tumor. Key features therefore are not only the specific recognition of the tumor cells by the immune cells, but also the generation of appropriate surrounding conditions for the development of an efficient antitumor immune response. This can be addressed by focusing on the complex network of ligands/cytokines and corresponding receptors that regulate the immune system. Amongst others, members of the B7/CD28-superfamily, TNF/TNFR-superfamily and cytokines/common γ-chain receptor family have shown great antitumor potential. We are interested in exploring how tumor-directed delivery and defined combination of such molecules can impact the therapeutic potential.

Targeted strategies with antibody-fusion proteins

Tumor targeting can be achieved by antibodies binding specifically to tumor associated antigens. This property makes recombinant antibodies a valuable tool for diverse targeted approaches. For example, bispecific antibodies can retarget effector cells to tumor cells, inducing artificially an antitumor immune response. Also, ligands or cytokines fused to recombinant antibodies can be directed to and presented at the tumor cell surface to immune cells, modulating their response. In order to improve the efficacy of such molecules at the tumor site we design antibody fusion proteins, focusing either on optimized presentation or a combined mode of action, analyzing their effect on immune cell populations in vitro and their antitumor potential in mouse models in vivo.

Publications

Selected research articles

 

Review articles

 

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 D. 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. 2th Dübel 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. Vol.2 pp. 113-126.

 

Lab members

PD Dr. Dafne Müller (Lab head)

Dr. Julie Moulliaux (PostDoc)

 

 

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

Funding

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