MIT engineers have developed a technique for reprogramming natural killer (NK) immune cells directly within the body, potentially avoiding the time-consuming and costly process of manufacturing modified cells outside it. Lipid nanoparticles deliver messenger RNA encoding chimeric antigen receptors, or CARs, which enable NK cells to recognise and destroy selected targets. Antibody fragments coating the particles help direct them towards receptors on NK cells.
In mouse experiments, approximately 80 per cent of the targeted NK cells were successfully reprogrammed. Three of five mice treated in a model of aggressive melanoma achieved complete remission. In a humanised mouse model of T cell lymphoma, tumours were eliminated after five injections. This outcome was comparable to treatment with CAR NK cells produced through the conventional process of removing, modifying and returning cells. In mice with autoimmune hepatitis, where autoreactive T cells attack liver cells, a single injection led to the destruction of those T cells and healing of liver damage.
The approach builds on strategies used for CAR T cell treatments, seven of which have received US Food and Drug Administration approval over the past decade. However, engineered T cells targeting T cell diseases can attack one another as well as diseased cells, a problem avoided by using NK cells. No CAR NK therapies currently have FDA approval. The researchers hope their method could eventually address other disorders driven by dysfunctional T cells, including multiple sclerosis and rheumatoid arthritis.
