Car Brake, Torwards a Safer CAR-T Therapy

CAR-T Therapy
CAR-T (chimeric antigen receptor T cell) therapy is one of the most promising treatment for cancer, with multiple ongoing clinical trials worldwide and 2 therapies approved by the FDA. The therapy engineers endogenous T cells from the patients with synthetic receptors for tumor antigens, giving them the ability to target tumor cells.

The Adverse Effects
However, without proper control after administration of CAR-T cells, severe adverse effects associated with CAR-T therapy may bring fatal risks to the patients, especially during the clinical trial stages. The side effects include cytokine release syndrome, on- target off-tumor toxicity and off-target toxicity.
Thus, methods to control the adverse effects are urgently needed.

Current Methods
To date the prevalent ways are to engineer suicide genes in CAR-T cells and remove transferred cell population when giving drugs. However, these methods could deplete CAR-T cells and completely halt the expensive treatment. Repeat the treatment may be a burden on the patients, both physically and financially.

What We Do——Braking Bad!
This year, team SYSU-CHINA aims to provide a safer yet affordable CAR-T therapy, by developing a reversible safe switch controlled by small molecules called CAR BRAKE. By expressing U24 protein of the human herpesvirus 6A under the control of tet-ON promoter, we can downregulate CAR molecules on the cell surface through endosomal recycling inhibition. This could potentially be used as a universal add-on for all CAR-Ts and TCR-Ts to ensure safety.