Informace o projektu
Improved chimeric antigen receptor T-cell designs for optimized therapy of genetically defined B-cell malignancies (iCART)

The iCART project will deliver comprehensive training-through-research to a talented postdoctoral fellow in state-of-the-art genome editing techniques, advanced primary cell culture methods and in vivo analysis complemented by well-structured training in generic skills over a 2 year period. The research part of the proposal intends to set up and optimize Chimeric Antigen Receptor (CAR) T-cell therapy, which is still being developed only to a limited extend in Europe. While achieving prolonged remissions in some difficult-to-treat patients with B-cell malignancies, CAR T-cell therapy still faces important technical issues related to laborious autologous transplant preparation, serious adverse side effects and lack of molecular markers predictive of the therapy outcome, which hamper its large-scale utilization. The proposed project aims to address the mentioned drawbacks and to focus on developing an exogenously regulated anti-CD19 CAR methodology for treatment of B-cell malignancies. Moreover, the prepared set of CAR T-cell transplants will be used for the first time to assess associations between the disease genetic drivers and the response to CAR treatment in both in vitro and in vivo disease models. By these means, the project aims to uncover novel predictive biomarkers of therapy outcome and to set the base for a more personalized CAR T-cell therapy. The expected output is to generate CAR designs for direct application in immunotherapy of genetically defined B-cell tumors. This innovative approach, in hands of local medical facilities specialized in treatment of B-cell malignancies, has a huge potential to strengthen the clinical innovation development of South Moravian Region. Thanks to the direct collaboration with University Hospital Brno, the iCART project could might have an immediate impact on medical care provided to patients and on strengthening the position of the hospital among the other clinical research institutions.