Researcher Database
Prof. Dr. Katharina Fleischhauer
Institute for Experimental Cellular Therapy
Hufelandstrasse 55
45122 Essen
Program
Cancer Immunotherapy (CI)
Summary
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the oldest and clinically most established form of cancer immunotherapy, in which immune cells from a healthy donor engrafted into the patient can provide efficient and long-lasting control of blood cancer cells surviving after chemotherapy. An important cellular subset mediating this graft-versus-leukemia (GvL) effect is represented by alloreactive T-cells recognizing mismatched histocompatibility (HLA) antigens on patient cells. Since mismatched HLA can be expressed both on neoplastic cells and on healthy tissues, the downside of GvL is graft-versus-host-disease (GvHD), one of the most relevant clinical complications after allo-HSCT. A better understanding of the molecular mechanisms underlying T-cell alloreacitivity is warranted to identify new strategies for dissecting GvL from GvHD, and for characterizing mechanisms of specific immune escape of relapsing blood cancers after allo-HSCT.
The University Hospital Essen has one of the most active clinical allo-HSCT departments, with over 200 such transplants performed every year. Taking advantage of this unique platform, the main research goals of the Institute of Experimental Cellular Therapy is to provide new insights into the role of peptide antigen processing, structural HLA variability and the alloreactive T-cell-receptor repertoire for GvL and GvHD, with particular regards to new mechanisms of immune evasion post-transplant.
DKTK Junior Group Leader for Cancer Systems Biology
Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance.
Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.