MIT researchers report in Nature Biotechnology that an injected lipid nanoparticle can reprogram NK cells in living mice to attack cancer and harmful T cells, though the work is preclinical and untested in people.
Researchers at MIT report that they have reprogrammed natural killer (NK) cells inside the body using an injectable nanoparticle, instead of the laborious laboratory manufacturing that today's cell therapies require. The study, published in Nature Biotechnology and led by senior author Daniel Anderson of MIT's Koch Institute, uses lipid nanoparticles that carry messenger RNA. The RNA instructs NK cells to build a chimeric antigen receptor (CAR), and antibody fragments on the particle surface steer it toward NK cells. The receptor can be retargeted: the team made versions aimed at CD19, a protein on B cells, and CD3, a protein on T cells, including those that drive autoimmune attacks.
The results so far come entirely from mice. According to the research summary, about 80 percent of the targeted NK cells were modified after injection. In mice with an aggressive melanoma, three of five treated animals reached complete remission. In humanized mice carrying T-cell lymphoma, tumors were eliminated after five injections, a result the team describes as comparable to conventionally made CAR NK cells. The researchers also tested the approach against autoimmune hepatitis, a condition in which abnormal T cells attack liver cells, and the summary reports that the treatment reversed liver damage in mice.
The idea matters because CAR T-cell therapies, of which the US FDA has approved seven, require doctors to collect a patient's blood, send it to a specialized facility, engineer and expand the cells, and return them for infusion. No CAR NK therapy has yet been approved. NK cells are attractive for diseases involving abnormal T cells because, unlike engineered T cells, they should not attack one another. Still, the findings are preclinical, the animal groups were small, and safety, durability and effectiveness in people are unknown; any move to human trials would be a later step, and the cost and simplicity benefits the authors envision remain a prospect rather than a result.
