Clinical Cooperation Unit Applied Tumor Biology

Prof. Dr. med. Magnus von Knebel Doeberitz

The Clinical Cooperation Unit Applied Tumor Biology is part of the Department of Applied Tumor Biology of Heidelberg University Hospital and also part of the Molecular Medicine Partner Unit of the European Molecular Biology Laboratory (MMPU-EMBL). Our major scientific interests relate to basic mechanisms of carcinogenesis triggered by human papillomaviruses and DNA mismatch repair deficiency that account for about 10 percent of all human cancers. We aim to identify diagnostic markers and therapeutic targets. We design and organize clinical trials to validate the clinical impact of respective markers and targets. Furthermore, we have successfully established “spin-off” companies to guarantee the “clinical translation” of scientific concepts into commercially available certified products. Examples of diagnostic markers developed by our group are p16INK4a and the CINtec® product line, which are used as diagnostic markers for HPV-induced lesions in histo- and cytopathology. Within the past few years, these markers became the new global gold standard in the diagnostics of HPV-associated neoplasms. In more recent work we explored a vaccine that targets p16INK4a as antigen. Initial clinical trials showed that this vaccine elicits substantial T-cell responses in patients without causing side effects. Further research activities are focusing on the epigenetic regulation of human papillomavirus infections as well as immune evasion strategies of HPV-triggered pre-cancers and cancers.

For DNA mismatch repair deficient (MSI-H) cancers we identified a new group of highly immunogenic frame shift induced antigens that were also successfully tested in a phase I/IIa clinical trial. Further research relates to immune evasion strategies of MSI-H cancers, particularly relevant for patients with the most abundant hereditary colorectal cancer syndrome (Lynch syndrome). For both examples we were able to develop new diagnostic tests as well as new therapeutic concepts based on the delineation of basic molecular mechanism triggering carcinogenesis. Based on our research we were able to develop clinical pipelines that led to the successful translation of basic concepts into clinically applicable new medical products.

Contact

Prof. Dr. med. Magnus von Knebel Doeberitz
Applied Tumor Biology (G105)
Tel: +49 6221 42 2487

Selected Publications

  • Bergeron C. et al. (2015). The clinical impact of using p16(INK4a) immunochemistry in cervical histopathology and cytology: an update of recent developments. Int J Cancer, 136(12), 2741–2751.
  • Reuschenbach M. et al. (2015). Methylation status of HPV16 E2-binding sites classifies subtypes of HPV-associated oropharyngeal cancers. Cancer, 121(12), 1966–1976.
  • Chaiwongkot A. et al. (2013). Differential methylation of E2 binding sites in episomal and integrated HPV 16 genomes in preinvasive and invasive cervical lesions. Int J Cancer, 132(9), 2087–2094.
  • Kloor M. et al. (2012). Prevalence of mismatch repair-deficient crypt foci in Lynch syndrome: a pathological study. Lancet Oncol, 13(6), 598–606.
to top