Research

Cellular Immunotherapy of onco-hematologic diseases

The adoptive transfer of immune cells with anti-neoplastic activity plays an important role for the immunotherapy of blood cancer. In this context, replacement of the patient’s blood system with that of a healthy donor, i.e., allogeneic hematopoieitic cell transplantation (HCT), represents the clinically most consolidated and increasingly successful treatment modality. Over recent years, adoptive transfer of genetically modified immune cells, in particular by chimeric antigen receptors (CAR) or T-cell receptors (TCR), have also been implemented into clinical practice.

The aim of our research is to unravel the key immunological mechanisms underlying the therapeutic efficacy but also the off-target negative side effects of allogeneic HCT and novel cell therapies, based on state of the art in vitro models. Central to our projects are the human leukocyte antigen (HLA) molecules, which are highly polymorphic and present peptides to specific immune receptors, thereby playing a key role in orchestrating the immune system. We investigate the functional relevance of peptide presentation by highly variable HLA on blood cancer cells, with a special focus on acute leukemias, their recognition by equally variable TCR, and mechanisms of immune evasion, in the context of modern cell therapies, in different central projects as follows.

1. The immunopeptidome of leukemia and its role for the recognition by alloreactive T cells after allogeneic HCT. Coordination: Pietro Crivello, M.Sc., PhD
2. Mining for TCR specific for processing-dependent immunogenic peptides. Coordination: Esteban Arrieta-Bolaños, M.Sc., PhD. Graduate Student: Kulvara Kittisares
3. T-cell responses against human cytomegalovirus and their role after allogeneic HCT. Coordiantion: Katharina Fleischhauer, MD (in collaboration with Mirko Trilling, PhD, Institute for Virology) Graduate Student: Luisa Betke
4. Characterization of hematopoiesis-specific alloreactive TCR for selective anti-tumor immunotherapy after allogneic HCT. Coordination: Thuja Arrieta-Bolaños, M.Sc., PhD ( substituted by Luisa Betke, M.Sc., PhD)
5. Development of CAR-T cells alloreactive to HLA-DP, for cellular immunotherapy of leukemia relapse after allogeneic HCT. Coordination: Pietro Crivello, M.Sc., PhD (in collaboration with Helmut Hanenberg, MD, Department of Pediatrics)
6. Retrospective testing of new concepts for the selection of unrelated stem cell donors, in collaboration with national and international donor registries DRST, EBMT and CIBMTR Coordiantion: Katharina Fleischhauer, MD