Genetic engineering of chimeric antigen receptor (CAR) T cells for immunotherapy in cancer and infection
We have recently established a cutting-edge non-viral chimeric antigen receptor (CAR) gene-transfer and genome editing platform to fine-tune the reactivity of CAR T cells to an optimal sweet-spot with maximum efficacy and safety. In this seed project, we will exploit this platform to knock-out the PD-1 check-point molecule (using CRISPR/Cas9 genome editing) that compromises the function of CAR T cells. We will determine the gain-of-function after PD-1 k.o in CAR T cells using established models of cancer (CARs: CD19 – leukemia/lymphoma; SLAMF7 – multiple myeloma; ROR1– breast cancer) and viral infection (CARs: CD19 – EBV; CD4 – HIV; gB – CMV) (WP1) and explore innovative methods for delivering genetic cargo to T cells in vitro and in vivo (WP2). This project provides the basis for subsequent systematic screening with CRISPR/Cas9 libraries to identify novel target loci for gene editing to enhance the therapeutic index of CAR T cells in cancer and infection.
Dr. Michael Hudecek & Prof. Hermann Einsele
Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
- Vaccinology and applied Microbiology- Prof. Dr. Carlos A. Guzmán