Using immune competent mouse models that are highly representative of human lymphoma, we are modeling clinical correlates of CD19 CAR T cell treatment failure. This helps us understand the underlying mechanisms and implement engineering solutions.

The introduction of a CAR confers a new specificity to a T cell, however, the native T cell receptor (TCR) remains intact in all approved autologous cell products, and thus CAR T cells have dual specificity. We are using vaccines to stimulate CAR T cells through their native T cell receptor to enhance engraftment and function and improve tumour control.

Currently approved CAR T cell therapies are manufactured in a bespoke manner by lentivirus or retrovirus transduction of autologous T cells ex vivo. While the approach has generated impressive clinical benefits, the financial burden and logistical difficulties with scalability have limited broad implementation. We are collaborating with local experts in RNA and lipid nanotechnology to develop strategies to generate CAR T cells in vivo.

We are testing novel CAR T cell designs and targets for the treatment of cancers and autoimmune diseases.