Division of Translational Oncology

Prof. Dr. Christof von Kalle

The NCT / DKTK MASTER Program. The program has enabled implementation of a standardized workflow for patient selection, sample processing, molecular and bioinformatic analysis, technical validation of individual findings, and reporting of results through a dedicated interdisciplinary molecular tumor board of translational oncologists and scientists from the NCT Heidelberg, NCT Dresden and DKTK partner sides. So far more than 700 patients with various tumor entities have been enrolled in this registry study and discussed in the interdisciplinary tumor board.
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The Division is deeply involved in the clinical activities of NCT and contributes to trial development, with a special focus on molecular diagnosis and therapy. Six physician scientists of the Division participate in patient care in outpatient clinics, tumor boards and clinical standard conferences and support diagnostic and therapeutic translation from DKFZ and HUMC into innovative clinical trials. Towards personalized oncology, the Division coordinates the development of the NCT Precision Oncology Program (NCT POP), which aims to provide a comprehensive high-throughput molecular analysis for every patient treated at the NCT. Within the frame of the NCT POP the Division drives the center-wide NCT MASTER (Molecularly Aided Stratification for Tumor Eradication) program that provides all components of a clinical implementation workflow for high-throughput molecular diagnostics and enrolment into basket trials with the explicit purpose of stratifying each patient for the best treatment or trial strategy. The research program of the Division focuses on Applied Stem Cell Research (Hanno Glimm), Molecular and Gene Therapy (Manfred Schmidt), Molecular and Cellular Oncology (Stefan Fröhling) and Virotherapy (Guy Ungerechts). In 2014 the company GeneWerk GmbH, a platform for DNA- or RNA-fusion sequences, was successfully founded out of the Division.

Future Outlook:
The Division will further develop its research focus in the field of normal and cancerous stem cell biology, insertional mutagenesis in cancer and gene therapeutic approaches. It aims to decipher mechanisms of tumor initiation, self-renewal, metastasis and heterogeneity of tumor-initiating cells and of step-wise malignant transformation in leukemogenesis. Assays for bulk and single-cell T- and B-cell receptor sequencing and bioinformatical analysis allow the identification of antigen-specific clones and the study of immune response dynamics in health and disease. Future clinical studies will include clonal monitoring of the T lymphocyte repertoire in immunotherapy and of gene corrected cells. Gene therapy vector characterization and eventual oncogenicity are also investigated to elucidate the role of genomic instability in carcinogenesis. The Molecular and Cellular Oncology group works to bring targeted approaches and molecularly based patient stratification to clinical trials and patient treatment. It also utilizes high-throughput functional genomics and large-scale proteomics to identify specific functional dependencies in AML and soft-tissue sarcomas, and to validate small molecules that can target these dependencies in preclinical models. The Virotherapy group is preparing a phase Ib/II trial combining oncolytic measles virus with immune checkpoint blockade as well as trials applying state-of-the-art immunotherapies accompanied by a translational research program.

Contact

Prof. Dr. Christof von Kalle
Translational Oncology (G100)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 460
69120 Heidelberg
Tel: +49 6221 56 6990

Selected Publications

  • Weischenfeldt J, et al. (2017). Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking. Nat Genet, 49(1):65-74.
  • Ruggiero E, et al. (2015). High-resolution analysis of the human T cell receptor repertoire. Nat Commun; 6:8081. DOI: 10.1038/ncomms9081.
  • Gabriel, R, et al. (2015). Mapping the precision of genome editing. Nat Biotechnol; 33(2):150-152.
  • Kaeppel C, et al. (2013). A largely random AAV integration profile after LPLD gene therapy. Nat Med; 19(7):889-91.
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