Torwards a safer 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. However, the 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. While suicide switches serve as common methods for controlling adverse effects, they completely halt the expensive treatment.
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.
In addition, we are also ambitious to provide a method for monitoring CAR-T activity, using synthetic NF-AT promoter and reporter genes.