Division of Translational Oncology

Prof. Dr. Christof von Kalle

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The Division of Translational Oncology coordinates major aspects of NCT’s further development and translational oncology at DKFZ. The department 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 Department participate in patient care in outpatient clinics, tumor boards and clinical standard conferences of the center, and support diagnostic and therapeutic translation from DKFZ and HUMS into innovative clinical trials. 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. It focuses on adult patients with rare systemic cancers or patients who are younger than 50 years with the explicit purpose of stratifying each patient for the best treatment or trial strategy.

The research program of the department focuses on Applied Stem Cell Research (Hanno Glimm), Molecular and Gene Therapy (Manfred Schmidt), Molecular and Cellular Oncology (Stefan Fröhling), Functional Genomics (Claudia Scholl), Lymphoma Research (Thorsten Zenz), and Virotherapy (Guy Ungerechts).

Towards personalized oncology, the Department 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 NCT. We have created a strategic development plan, NCT 3.0, together with our colleagues, which will be funded by the federal government with up to €40 million annually. This will provide essential resources for the development of NCT Heidelberg and its partner site NCT Dresden into an oncology center of excellence for precision oncology.

FUTURE OUTLOOK
The Division will further develop its research program 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.
Structural and functional genomics and innovative treatment approaches target individual genetic lesions. Future clinical studies will include real-time, high-throughput clonal monitoring of the T lymphocyte repertoire in immunotherapy and of gene corrected cells. New vector systems allowing either reduced integration efficiency (integrase-deficient lentiviral vectors) and/or targeted integration in specific safe genomic locations (zinc finger nucleases) are being developed. Elucidation of genomic instability and the role of double-strand breaks in carcinogenesis are rapidly growing direct extensions of this work. Functional genomics studies (shRNA and CRISPR/Cas9 screens) aim at identifying a novel Achilles’ heel of high risk chronic lymphocytic leukemia with the ultimate goal to develop new therapeutic strategies breaking therapy resistance. Furthermore, the virotherapy group develops vectors which selectively lyse tumor cells and support induction of anti-tumor immune responses, thereby enabling targeted, safe and specific immunomodulation in the tumor microenvironment. A phase Ib/II trial combining oncolytic measles virus with immune checkpoint blockade and latest trials for molecular and immunotherapeutic interventions will be initiated in the near future.

Contact

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

Selected Publications

  • Dietrich S, Pircher A, Endris V, Peyrade F, Wendtner CM, Follows GA, Hüllein J, Jethwa A, Ellert E, Walther T, Liu X, Dyer MJ, Elter T, Brummer T, Zeiser R, Hermann M, Herold M, Weichert W, Dearden C, Haferlach T, Seiffert M, Hallek M, von Kalle C, Ho AD, Gaehler A, Andrulis M, Steurer M, Zenz T. BRAF inhibition in hairy cell leukemia with low dose vemurafenib. Blood. 2016 Mar 3. pii: blood-2015-11-680074.
  • Ruggiero E, Nicolay JP, Fronza R, Arens A, Paruzynski A, Nowrouzi A, Ürenden G, Lulay C, Schneider S, Goerdt S, Glimm H, Krammer PH, Schmidt M, von Kalle C. High-resolution analysis of the human T-cell receptor repertoire. Nat Commun 2015; 6:8081. DOI: 10.1038/ncomms9081.
  • Gabriel, R, von Kalle, C, Schmidt, M. Mapping the precision of genome editing. Nat Biotechnol 2015; 33(2):150-152.
  • Kaeppel C, Beattie SG, Fronza R, van Logtenstein R, Salmon F, Schmidt S, Wolf S, Nowrouzi A, Glimm H, von Kalle C, Petry H, Gaudet D, Schmidt M. A largely random AAV integration profile after LPLD gene therapy. Nat Med 2013; 19(7):889-91.
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