A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy
A new type of molecular emergency brake could help improve the safety of cellular immunotherapies for cancer patients.
T cells engineered with tumour-targeting constructs known as chimeric antigen receptors (CARs) offer a potent way to supercharge the immune system against cancer. But the therapies carry a risk of runaway immune responses against healthy tissues.
A team that included scientists from the Korea Advanced Institute of Science and Technology (KAIST) has now designed CAR T cells that can be reversibly inactivated with drugs.
The researchers split the conventional CAR construct in two and introduced a linker chain made of interacting domains that spontaneously come together inside the cell to promote T cell activation, but are kept apart in the presence of certain small-molecule drugs.
The researchers validated their system in human prostate-cancer cells and in a mouse model of the disease.
- Nature Biotechnology 38, 426–432 (2020). doi: 10.1038/s41587-019-0403-9