Advances in genome editing through processes such as CRISPR, and the ability to rewire cells through synthetic biology, have led to increasingly elaborate approaches for modifying and supercharging T cells for therapy. Such techniques are providing tools to counter some of the limitations of current CAR-T therapies, which are expensive to make, can have dangerous side effects, and have so far been successful only against blood cancers.
CAR-T therapies capitalize on the activities of T cells, the immune system’s natural hunters that prowl through the body looking for things that don’t belong. Foreign cells, or those infected with a virus, express unusual proteins that serve as a beacon to T cells, some of which release a toxic stew of molecules to destroy the abnormal cells. This search-and-destroy function can also target cancer cells for elimination, but tumours often have ways of disarming the immune system, such as by cloaking abnormal proteins or suppressing T-cell function.
CAR-T cells carry synthetic proteins — the chimeric antigen receptors — that span the cell membrane. On the outside is a structure that functions like an antibody, binding to specific molecules on the surface of some cancer cells. Once that has bound, the portion of the protein inside the cell stimulates T-cell activity, hot-wiring it into action. The result is a tiny, revved-up, cancer-fighting machine.