The hypothesis of this project is that split CAR T cells (dual targeting) with improved capacity to home to the bone marrow niche by additional expression of a chemokine receptor will be an efficient and highly specific strategy to eliminate AML (MRD and LSCs).

The researcher will assess primary AML (stem) cell antigen profiles from AML patient samples (various subtypes) at diagnosis, after therapy and at relapse, but also from healthy normal HSCs, using scRNA sequencing and proteomics.

Combinations of novel antigens and/or those previously identified by us and/or the network partners will be chosen based on specificity (MRD and LSCs) versus healthy (hematopoietic) cells. Chemokine receptors to generate BM homing capacity of the CARs will be chosen and concurrent assessment of primary BM samples will be performed. For further evaluation of CAR T cell specificity and function, e.g., cytotoxicity, metabolism, proliferative capacity, LSC specificity and homing, the researcher will utilize an ex vivo long-term culture system for primary AML (MRD) cells and the “organ-on-a-chip” 3D.

Cell tracing and quantification based on stable chemotactic gradients over time will be done to evaluate chemokine receptors for bone marrow homing. Promising dual targeting CAR-T constructs will be functionally tested in vivo in AML PDX mouse, and homing to the bone marrow will be assessed by live imaging. 

Host:

University Hospital München, München, Germany

Supervisor:

Prof. Marion Subklewe 

Duration:

48 months, starting 1-5-2025

Profile doctoral candidate:

Master’s degree in life sciences, other (bio)medical sciences, or related, and practical experience in cell biology and molecular biology.  

In addition:

Interns are planned to MIMETAS (Netherlands, 3 months, supervisor Karla Queiroz) to test CAR T cell therapies in the 3D AML MRD model, and to the University of Sevilla (Spain, 3 months, supervisor Simon Mendez-Ferrer) to test CAR T cells for homing to the bone marrow.