Chimeric Antigen Receptor (CAR) T cells achieved remarkable success in treating B-cell malignancies, yet, their long-term efficiency does not hold up to the original promises. Novel designs of CAR-T cells are urgently needed with further genetic editing for enhanced activity and persistence.
We will elucidate the precise function of RASAL3, a negative regulator of T-cell signaling, and will assess its potential for augmenting CAR-T cell activity. We will generate RASAL3 knockout CAR-T cells to evaluate their signaling, activation strength and killing potential against malignant B cell lines in vitro and their activity, persistence and long-term effect in a mouse model. In addition, using a CRISPR/Cas9 knockout library, we will interrogate genes on a genome-wide level that are able to modulate and fully unleash the activity of CAR-T cells. Identified genes will be thoroughly validated and the underlying molecular mechanisms elucidated. They will be used to develop innovative designs of CAR-T cells, whose performance will be evaluated both in vitro and in vivo.

Sustainable Development Goals

Masaryk University is committed to the UN Sustainable Development Goals, which aim to improve the conditions and quality of life on our planet by 2030.