MIT engineers have developed a technique for generating engineered natural killer (NK) cells directly inside the body, potentially bypassing the costly, time-consuming process of modifying cells in a laboratory. Their lipid nanoparticles deliver messenger RNA encoding chimeric antigen receptors, or CARs, which enable NK cells to recognize and destroy selected targets. Antibody fragments coating the particles guide them to receptors on NK cells. In mouse experiments, approximately 80 percent of the targeted NK cells were successfully reprogrammed.
The approach produced results across several disease models. Three of five treated mice with aggressive melanoma achieved complete remission. In a humanized mouse model of T cell lymphoma, tumors were eliminated after five injections, with results similar to those obtained with conventionally manufactured CAR NK cells. These mice had received human blood cells, temporarily creating a human-like immune system. In mice with autoimmune hepatitis, where autoreactive T cells attack liver cells, a single injection destroyed the harmful T cells and allowed liver damage to heal.
The strategy builds on engineered immune-cell therapies. Over the past decade, the US Food and Drug Administration has approved seven CAR T cell cancer treatments, which have been particularly successful against blood cancers originating from B cells. However, T cells engineered to attack T cell proteins may also kill one another, a problem that does not arise when NK cells target T cells. Although no CAR NK therapies currently have FDA approval, the researchers hope their approach could eventually address other autoimmune disorders involving dysfunctional T cells, including multiple sclerosis and rheumatoid arthritis.
