MIT engineers have devised a method that uses lipid nanoparticles (LNPs) to deliver messenger RNA directly to NK cells inside the body, converting them into chimeric antigen receptor (CAR) NK cells without extracting the cells. The mRNA‑encoded CAR protein enables NK cells to recognize and destroy abnormal T cells, including cancerous and autoreactive T cells.
In mouse studies the approach proved effective: about 80% of the targeted NK cells were reprogrammed; in an aggressive melanoma model three out of five mice achieved complete remission; in a humanized mouse model of T‑cell lymphoma, five consecutive injections eliminated the tumors; and in an autoimmune hepatitis model a single injection removed the pathogenic T cells and allowed liver tissue to heal. Compared with the conventional ex‑vivo production of CAR NK cells, the in‑vivo delivery cuts time and cost, avoids the complex steps of cell extraction, culture, and reinfusion, and sidesteps the self‑killing issue that hampers CAR‑T therapies for T‑cell diseases.
The investigators suggest the platform could be extended to other T‑cell‑driven autoimmune conditions such as multiple sclerosis and rheumatoid arthritis. The work was funded by Sanofi, the Marble Center for Cancer Nanomedicine, and a core grant from the National Cancer Institute.
Review: This study highlights the power of nanodelivery for immune‑cell engineering, offering a simpler and cheaper route to treat both cancer and autoimmune disorders, and merits further clinical investigation.