Encouraging grant 2021 'Rosa Blanckaert' for young researchers: (Bio)Medical Sciences.

Chimeric antigen receptor (CAR)-T cell therapy has demonstrated unprecedented clinical activity in patients with hematological diseases, but a large proportion of them will ultimately relapse. Further optimization of this new treatment modality is therefore required to unlock its full therapeutic potential. In this project, in addition to using readily available cell line models, we will use our mRNA electroporation technology for CAR loading of immune cells. This will provide a rapid and efficient way to explore new research paths that can lead to optimized CAR-based cellular therapies for hematological diseases. Will assess the value of a multi-targeted approach incorporating two established CAR targets (CD19 and B-cell maturation antigen) and the novel CAR candidate CD200. Next, the hinge and co-stimulatory domains in the CAR structures will be sequentially modified, comparing conventional hinge and co-stimulatory domains with our recently discovered 4-1BB-hinge and CD26 co-stimulatory domains. Exhaustion will be prevented by introducing programmed death (PD-1) silencing RNA in the CAR-modified cells to reduce PD-1-mediated co-inhibitory signaling. Finally, positive findings will be translated from our cell line models to conventional T cells, NK cells and gdT cells.

Keywords:HEMATOLOGICAL NEOPLASMS, CHIMERIC ANTIGEN RECEPTORS, IMMUNOTHERAPY

Disciplines:Cellular therapy, Gene and molecular therapy, Hematology, Applied immunology, Cancer therapy