Projects & Grants
| Development of highly effective allogenic CAR T-cells based on innovative surface proteome analysis and non-viral approaches | |
|---|---|
| Project Id | NW25-03-00298 |
| Main solver | Jamal Alzubi, PhD |
| Period | 5/2025 - 12/2028 |
| Provider | Agentura zdravotnického výzkumu ČR |
| State | solved |
| Anotation | Cell therapies based on chimeric antigen receptor (CAR) T-cells represent a modern, highly promising direction in the treatment of cancer. In this project we would like to further improve both cytotoxic efficiency and on-target specificity of allogenic CAR T-cells by applying the state-of-the-art molecular, cellular, proteomic and in vivo approaches. Particularly, we plan to identify specific T-cell subsets responsible for efficient tumor lysis. Additionally, we will investigate the CAR-based immunological synapse by identification of plasma membrane proteins laterally associated with CARs and their target proteins to uncover potential novel biomarkers and/or immunotargets. Furthermore, we plan to develop novel bispecific CARs and hybrid T-cell receptors (hTCR) targeting the newly found antigens in multiple myeloma. The application of enhanced CARs and hTCRs might eliminate development of therapy resistance related to antigen escape. The newly created receptors will be introduced into primary, allogenic T-cells using the CRISPR-Cas9 technology combined with homology directed repair. This innovative methodology will allow a precise replacement of endogenous TRAC and HLA genes with CAR or another gene. The ultimate goal of this project is creation of a novel, highly effective, affordable and safe allogenic CAR T-cells avoiding viral vectors. |
