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Denis Schewe Group

Translational research in childhood leukemia, from disease mechanisms to novel immunotherapies

Portrait Denis Schewe

Childhood acute lymphoblastic leukemia is the most common malignancy in children. Despite a continuous rise in cure rates in the last decades, a significant proportion of patients relapse. Relapsing disease is poorly understood and some situations in leukemia therapy remain highly problematic. Examples include relapse after hematopoietic stem cell transplantation, relapsed/refractory T-ALL, KMT2A-rearranged infant leukemia or extramedullary disease. My working group has been eager to learn about these situations since 2011 and focused on in vivo modeling of ALL, novel antibody-mediated approaches and niche-dependent survival and resistance mechanisms. With a long-standing track record in high-end pediatric oncology research, the group is always looking for enthusiastic new PhD candidates willing to embark on projects with a high immediate clinical relevance for children with cancer.

Antibody-mediated immunotherapy of ALL

The objective of these projects are the design of novel antibody-based immunotherapies and immunotherapy combinations to make ALL therapy more effective, more specific and less toxic. We work with antibodies repurposed for ALL treatment from other indications, novel constructs developed in academia and industry collaborations as well as with antibody/targeted drug combinations, which are aimed at activating immune effector mechanisms.

Niche-dependent survival and resistance mechanisms in ALL

The aim of this projects is to identify mechanisms of chemoresistance and cellular survival in protected niches in leukemia, mainly in extramedullary compartments. In the last years and decades we have identified a number of signaling pathways and target molecules relevant for central nervous infiltration. Also, we are investigating the mechanisms of testicular leukemia. Extramedullary leukemia is a major problem in ALL therapy because its therapy can be highly toxic and is associated with various long-term sequelae. We aim to replace this therapy with more targeted approaches.

Denis Schewe Research – Figure
Figure: Phagocytosis of refractory primary T-cell acute lymphoblastic leukemia cells (red) by human macrophages (green) induced by a novel IL7R-targeting antibody (right panel, arrows). Lenk et al., Blood, 2024

Future Projects and Goals

  • Exploring novel targets and modalities for antibody-based immunotherapy of ALL and other hematological malignancies.
  • Exploring the contribution of immune effector cells on the efficacy of immunotherapy in ALL and how these could be efficiently modulated.
  • Understanding mechanisms of extramedullary leukemia and identifying novel targeting approaches.
  • Improving modeling of acute lymphoblastic leukemia and other hematological malignancies in order to reduce the need for in vivo experiments.

Methodological and Technical Expertise

  • Cell culture models of leukemia and co-culture models (bone marrow, CNS, and others)
  • Immunological methods (flow ctometry, FACS sorting, ELISA, Western Blot, and others)
  • In vitro immune effector cell assays (ADCC, AD)
  • Live cell imaging
  • In vivo leukemia patient-derived xenograft models in different immunodeficient mice strains
  • Biobank access to pediatric acute lymphoblastic leukemia cells


Since 05/2024
W3-Professor for Pediatrics and Pediatric Hematology/Oncology, TU Dresden

W3-Professor for Pediatrics, Otto-von-Guericke University Magdeburg

Professor of Pediatrics, Christian-Albrechts University Kiel

Habilitation in Pediatrics, Christian-Albrechts University Kiel

Max-Eder Junior Research Group Leader, Deutsche Krebshilfe, Pediatric Hematology/Oncology, UKSH Kiel

Postdoc, Mildred-Scheel program Deutsche Krebshilfe, Department of Biomedical Sciences, University at Albany, State University of New York and Mount Sinai Medical Center in New York City (Lab of Julio Aguirre-Ghiso, PhD)

MD, LMU München,“summa cum laude”

Selected Publications

Lenk L, Baccelli I, Laqua A, Heymann J, Reimer C, Dietterle A, Winterberg D, Mary C, Corallo F, Taurelle J, Narbeburu E, Neyton SL, Déramé M, Pengam S, Vogiatzi F, Bornhauser B, Bourquin JP, Raffel S, Dovhan V, Schüler T, Escherich G, den Boer ML, Boer JM, Wessels W, Peipp M, Alten J, Antić Ž, Bergmann AK, Schrappe M, Cario G, Brüggemann M, Poirier N, Schewe DM
The IL-7R antagonist Lusvertikimab reduces leukemic burden in xenograft-ALL via antibody-dependent cellular phagocytosis
Blood. blood.2023021088 doi: 10.1182/blood.2023021088 Epub ahead of print (2024)

Schewe DM, Vogiatzi F, Münnich IA, Zeller T, Windisch R, Wichmann C, Müller K, Bhat H, Felix E, Mougiakakos D, Bruns H, Lenk L, Valerius T, Humpe A, Peipp M, Kellner C
Enhanced potency of immunotherapy against B-cell precursor acute lymphoblastic leukemia by combination of an Fc-engineered CD19 antibody and CD47 blockade
Hemasphere 8(2):e48 doi: 10.1002/hem3.48 (2024)

Lenk L, Winterberg D, Vogiatzi F, Laqua A, Spory L, Mayar A, Dietterle A, Münch G, Vokuhl C, Richter J, Polson AG, Schüler T, Kahlert UD, Peipp M, Valerius T, Schrappe M, Cario G, Jumaa H, Hobeika E, Brüggemann M, Alsadeq A, Schewe DM
Preclinical Evidence for the Efficacy of CD79b Immunotherapy in B-cell Precursor Acute Lymphoblastic Leukemia
Hemasphere 6(8):e754. doi: 10.1097/HS9.0000000000000754 (2022)

Müller K, Vogiatzi F, Winterberg D, Rösner T, Lenk L, Bastian L, Gehlert CL, Autenrieb MP, Brüggemann M, Cario G, Schrappe M, Kulozik AE, Eckert C, Bergmann AK, Bornhauser B, Bourquin JP, Valerius T, Peipp M, Kellner C, Schewe DM
Combining daratumumab with CD47 blockade prolongs survival in preclinical models of pediatric T-ALL
Blood 140(1):45–57. doi: 10.1182/blood.2021014485 (2022)

Vogiatzi F, Winterberg D, Lenk L, Buchmann S, Cario G, Schrappe M, Peipp M, Richter-Pechanska P, Kulozik AE, Lentes J, Bergmann AK, Valerius T, Frielitz FS, Kellner C, Schewe DM
Daratumumab eradicates minimal residual disease in a preclinical model of pediatric T-cell acute lymphoblastic leukemia
Blood 134(8):713–716. doi: 10.1182/blood.2019000904 (2019)