Research Projects

Chimeric antigen receptor (CAR) T cells therapy has been successful in relapsed or refractory acute lymphoblastic leukaemia and diffuse large B-cell lymphomas, but it has many limitations primarily due to its reduced trafficking and persistence as well as its exhaustion at the tumour site. We propose to enhance anti-tumour potential of CAR T cells by engineering the CAR receptor. Essentially, a genetically engineered CAR will be designed to express domain of EZHIP (Enhancer of Zeste Homologs Inhibitory Protein) that will inhibit PRC2 (Polycomb Repressive Complex 2) activity. In turn, this will reduce H3K27me3, a repressive histone modification in CAR T cells, which may enhance its anti-tumour functionality against tumours by regulating gene expression program. Ultimately, we intend to modify the epigenome of CAR T cells to enhance its efficacy for tumours. To address this, we will use CD19 expressing tumor cells as our model system with anti CD19 CAR T cells as effector T cells. We propose that inhibiting H3K27me3 in CAR T cells will lead to its improved effector functions against haematological tumours. The concept will be further developed for other tumour subtypes.